CINXE.COM

<!DOCTYPE html> <html > <head> <meta charset="utf-8"> <meta rel="search" type="application/opensearchdescription+xml" href="/open_search.xml" title="Academia.edu"> <meta content="width=device-width, initial-scale=1" name="viewport"> <meta name="google-site-verification" content="bKJMBZA7E43xhDOopFZkssMMkBRjvYERV-NaN4R6mrs"> <meta name="csrf-param" content="authenticity_token" /> <meta name="csrf-token" content="7crAfQLTQW9B8a4-ghCwtnCSdhqExhcRORhsHnxp7qVZI_FOCn_-K_fXMPI9KXVqX4E8Rn4JTNnDOJoH2qZ1kw" /> <meta name="citation_title" content="metabolites Unraveling Biochemical Pathways Affected by M itochondrial Dysfunctions Using M etabolomic Approaches" /> <meta name="citation_author" content="Patricia Renard" /> <meta name="citation_author" content="Martine Raes" /> <meta name="twitter:card" content="summary" /> <meta name="twitter:url" content="https://www.academia.edu/33009414/metabolites_Unraveling_Biochemical_Pathways_Affected_by_M_itochondrial_Dysfunctions_Using_M_etabolomic_Approaches" /> <meta name="twitter:title" content="metabolites Unraveling Biochemical Pathways Affected by M itochondrial Dysfunctions Using M etabolomic Approaches" /> <meta name="twitter:description" content="Mitochondrial dysfunction(s) (MDs) can be defined as alterations in the mitochondria, including mitochondrial uncoupling, mitochondrial depolarization, inhibition of the mitochondrial respiratory chain, mitochondrial network fragmentation," /> <meta name="twitter:image" content="http://a.academia-assets.com/images/twitter-card.jpeg" /> <meta property="fb:app_id" content="2369844204" /> <meta property="og:type" content="article" /> <meta property="og:url" content="https://www.academia.edu/33009414/metabolites_Unraveling_Biochemical_Pathways_Affected_by_M_itochondrial_Dysfunctions_Using_M_etabolomic_Approaches" /> <meta property="og:title" content="metabolites Unraveling Biochemical Pathways Affected by M itochondrial Dysfunctions Using M etabolomic Approaches" /> <meta property="og:image" content="http://a.academia-assets.com/images/open-graph-icons/fb-paper.gif" /> <meta property="og:description" content="Mitochondrial dysfunction(s) (MDs) can be defined as alterations in the mitochondria, including mitochondrial uncoupling, mitochondrial depolarization, inhibition of the mitochondrial respiratory chain, mitochondrial network fragmentation," /> <meta property="article:author" content="https://unamur.academia.edu/MRaes" /> <meta property="article:author" content="https://independent.academia.edu/PatriciaRenard" /> <meta name="description" content="Mitochondrial dysfunction(s) (MDs) can be defined as alterations in the mitochondria, including mitochondrial uncoupling, mitochondrial depolarization, inhibition of the mitochondrial respiratory chain, mitochondrial network fragmentation," /> <title>(PDF) metabolites Unraveling Biochemical Pathways Affected by M itochondrial Dysfunctions Using M etabolomic Approaches</title> <link rel="canonical" href="https://www.academia.edu/33009414/metabolites_Unraveling_Biochemical_Pathways_Affected_by_M_itochondrial_Dysfunctions_Using_M_etabolomic_Approaches" /> <script async src="https://www.googletagmanager.com/gtag/js?id=G-5VKX33P2DS"></script> <script> window.dataLayer = window.dataLayer || []; function gtag(){dataLayer.push(arguments);} gtag('js', new Date()); gtag('config', 'G-5VKX33P2DS', { cookie_domain: 'academia.edu', send_page_view: false, }); gtag('event', 'page_view', { 'controller': "single_work", 'action': "show", 'controller_action': 'single_work#show', 'logged_in': 'false', 'edge': 'unknown', // Send nil if there is no A/B test bucket, in case some records get logged // with missing data - that way we can distinguish between the two cases. // ab_test_bucket should be of the form <ab_test_name>:<bucket> 'ab_test_bucket': null, }) </script> <script> var $controller_name = 'single_work'; var $action_name = "show"; var $rails_env = 'production'; var $app_rev = 'bbdb80613189ba697977787ab78246749f444764'; var $domain = 'academia.edu'; var $app_host = "academia.edu"; var $asset_host = "academia-assets.com"; var $start_time = new Date().getTime(); var $recaptcha_key = "6LdxlRMTAAAAADnu_zyLhLg0YF9uACwz78shpjJB"; var $recaptcha_invisible_key = "6Lf3KHUUAAAAACggoMpmGJdQDtiyrjVlvGJ6BbAj"; var $disableClientRecordHit = false; </script> <script> window.require = { config: function() { return function() {} } } </script> <script> window.Aedu = window.Aedu || {}; window.Aedu.hit_data = null; window.Aedu.serverRenderTime = new Date(1740480755000); window.Aedu.timeDifference = new Date().getTime() - 1740480755000; </script> <script type="application/ld+json">{"@context":"https://schema.org","@type":"ScholarlyArticle","abstract":"Mitochondrial dysfunction(s) (MDs) can be defined as alterations in the mitochondria, including mitochondrial uncoupling, mitochondrial depolarization, inhibition of the mitochondrial respiratory chain, mitochondrial network fragmentation, mitochondrial or nuclear DNA mutations and the mitochondrial accumulation of protein aggregates. All these MDs are known to alter the capacity of ATP production and are observed in several pathological states/diseases, including cancer, obesity, muscle and neurological disorders. The induction of MDs can also alter the secretion of several metabolites, reactive oxygen species production and modify several cell-signalling pathways to resolve the mitochondrial dysfunction or ultimately trigger cell death. Many metabolites, such as fatty acids and derived compounds, could be secreted into the blood stream by cells suffering from mitochondrial alterations. In this review, we summarize how a mitochondrial uncoupling can modify metabolites, the signalling pathways and transcription factors involved in this process. We describe how to identify the causes or consequences of mitochondrial dysfunction using metabolomics (liquid and gas chromatography associated with mass spectrometry analysis, NMR spectroscopy) in the obesity and insulin resistance thematic. OPEN ACCESS","author":[{"@context":"https://schema.org","@type":"Person","name":"Martine Raes","url":"https://unamur.academia.edu/MRaes"},{"@context":"https://schema.org","@type":"Person","name":"Patricia Renard","url":"https://independent.academia.edu/PatriciaRenard"}],"contributor":[{"@context":"https://schema.org","@type":"Person","name":"Patricia Renard","url":"https://independent.academia.edu/PatriciaRenard"}],"dateCreated":"2017-05-14","dateModified":"2025-02-01","headline":"metabolites Unraveling Biochemical Pathways Affected by M itochondrial Dysfunctions Using M etabolomic Approaches","image":"https://attachments.academia-assets.com/53122800/thumbnails/1.jpg","inLanguage":"en","keywords":["Review","Mitochondrial dysfunction"],"publisher":{"@context":"https://schema.org","@type":"Organization","name":null},"sourceOrganization":[{"@context":"https://schema.org","@type":"EducationalOrganization","name":"unamur"},{"@context":"https://schema.org","@type":"EducationalOrganization","name":null}],"thumbnailUrl":"https://attachments.academia-assets.com/53122800/thumbnails/1.jpg","url":"https://www.academia.edu/33009414/metabolites_Unraveling_Biochemical_Pathways_Affected_by_M_itochondrial_Dysfunctions_Using_M_etabolomic_Approaches"}</script><style type="text/css">@media(max-width: 567px){:root{--token-mode: Rebrand;--dropshadow: 0 2px 4px 0 #22223340;--primary-brand: #0645b1;--error-dark: #b60000;--success-dark: #05b01c;--inactive-fill: #ebebee;--hover: #0c3b8d;--pressed: #082f75;--button-primary-fill-inactive: #ebebee;--button-primary-fill: #0645b1;--button-primary-text: #ffffff;--button-primary-fill-hover: #0c3b8d;--button-primary-fill-press: #082f75;--button-primary-icon: #ffffff;--button-primary-fill-inverse: #ffffff;--button-primary-text-inverse: #082f75;--button-primary-icon-inverse: #0645b1;--button-primary-fill-inverse-hover: #cddaef;--button-primary-stroke-inverse-pressed: #0645b1;--button-secondary-stroke-inactive: #b1b1ba;--button-secondary-fill: #eef2f9;--button-secondary-text: #082f75;--button-secondary-fill-press: #cddaef;--button-secondary-fill-inactive: #ebebee;--button-secondary-stroke: #cddaef;--button-secondary-stroke-hover: #386ac1;--button-secondary-stroke-press: #0645b1;--button-secondary-text-inactive: #b1b1ba;--button-secondary-icon: #082f75;--button-secondary-fill-hover: #e6ecf7;--button-secondary-stroke-inverse: #ffffff;--button-secondary-fill-inverse: rgba(255, 255, 255, 0);--button-secondary-icon-inverse: #ffffff;--button-secondary-icon-hover: #082f75;--button-secondary-icon-press: #082f75;--button-secondary-text-inverse: #ffffff;--button-secondary-text-hover: #082f75;--button-secondary-text-press: #082f75;--button-secondary-fill-inverse-hover: #043059;--button-xs-stroke: #141413;--button-xs-stroke-hover: #0c3b8d;--button-xs-stroke-press: #082f75;--button-xs-stroke-inactive: #ebebee;--button-xs-text: #141413;--button-xs-text-hover: #0c3b8d;--button-xs-text-press: #082f75;--button-xs-text-inactive: #91919e;--button-xs-icon: #141413;--button-xs-icon-hover: #0c3b8d;--button-xs-icon-press: #082f75;--button-xs-icon-inactive: #91919e;--button-xs-fill: #ffffff;--button-xs-fill-hover: #f4f7fc;--button-xs-fill-press: #eef2f9;--buttons-button-text-inactive: #91919e;--buttons-button-focus: #0645b1;--buttons-button-icon-inactive: #91919e;--buttons-small-buttons-corner-radius: 16px;--buttons-small-buttons-l-r-padding: 20px;--buttons-small-buttons-height: 48px;--buttons-small-buttons-gap: 8px;--buttons-small-buttons-icon-only-width: 48px;--buttons-small-buttons-icon-size: 20px;--buttons-small-buttons-stroke-default: 1px;--buttons-small-buttons-stroke-thick: 2px;--buttons-large-buttons-l-r-padding: 32px;--buttons-large-buttons-height: 64px;--buttons-large-buttons-icon-only-width: 64px;--buttons-large-buttons-icon-size: 20px;--buttons-large-buttons-gap: 8px;--buttons-large-buttons-corner-radius: 16px;--buttons-large-buttons-stroke-default: 1px;--buttons-large-buttons-stroke-thick: 2px;--buttons-extra-small-buttons-l-r-padding: 8px;--buttons-extra-small-buttons-height: 32px;--buttons-extra-small-buttons-icon-size: 16px;--buttons-extra-small-buttons-gap: 4px;--buttons-extra-small-buttons-corner-radius: 8px;--buttons-stroke-default: 1px;--buttons-stroke-thick: 2px;--background-beige: #f9f7f4;--error-light: #fff2f2;--text-placeholder: #6d6d7d;--stroke-dark: #141413;--stroke-light: #dddde2;--stroke-medium: #535366;--accent-green: #ccffd4;--accent-turquoise: #ccf7ff;--accent-yellow: #f7ffcc;--accent-peach: #ffd4cc;--accent-violet: #f7ccff;--accent-purple: #f4f7fc;--text-primary: #141413;--secondary-brand: #141413;--text-hover: #0c3b8d;--text-white: #ffffff;--text-link: #0645b1;--text-press: #082f75;--success-light: #f0f8f1;--background-light-blue: #f4f7fc;--background-white: #ffffff;--premium-dark: #877440;--premium-light: #f9f6ed;--stroke-white: #ffffff;--inactive-content: #b1b1ba;--annotate-light: #a35dff;--annotate-dark: #824acc;--grid: #eef2f9;--inactive-stroke: #ebebee;--shadow: rgba(34, 34, 51, 0.25);--text-inactive: #6d6d7d;--text-error: #b60000;--stroke-error: #b60000;--background-error: #fff2f2;--background-black: #141413;--icon-default: #141413;--icon-blue: #0645b1;--background-grey: #dddde2;--icon-grey: #b1b1ba;--text-focus: #082f75;--brand-colors-neutral-black: #141413;--brand-colors-neutral-900: #535366;--brand-colors-neutral-800: #6d6d7d;--brand-colors-neutral-700: #91919e;--brand-colors-neutral-600: #b1b1ba;--brand-colors-neutral-500: #c8c8cf;--brand-colors-neutral-400: #dddde2;--brand-colors-neutral-300: #ebebee;--brand-colors-neutral-200: #f8f8fb;--brand-colors-neutral-100: #fafafa;--brand-colors-neutral-white: #ffffff;--brand-colors-blue-900: #043059;--brand-colors-blue-800: #082f75;--brand-colors-blue-700: #0c3b8d;--brand-colors-blue-600: #0645b1;--brand-colors-blue-500: #386ac1;--brand-colors-blue-400: #cddaef;--brand-colors-blue-300: #e6ecf7;--brand-colors-blue-200: #eef2f9;--brand-colors-blue-100: #f4f7fc;--brand-colors-gold-500: #877440;--brand-colors-gold-400: #e9e3d4;--brand-colors-gold-300: #f2efe8;--brand-colors-gold-200: #f9f6ed;--brand-colors-gold-100: #f9f7f4;--brand-colors-error-900: #920000;--brand-colors-error-500: #b60000;--brand-colors-success-900: #035c0f;--brand-colors-green: #ccffd4;--brand-colors-turquoise: #ccf7ff;--brand-colors-yellow: #f7ffcc;--brand-colors-peach: #ffd4cc;--brand-colors-violet: #f7ccff;--brand-colors-error-100: #fff2f2;--brand-colors-success-500: #05b01c;--brand-colors-success-100: #f0f8f1;--text-secondary: #535366;--icon-white: #ffffff;--background-beige-darker: #f2efe8;--icon-dark-grey: #535366;--type-font-family-sans-serif: DM Sans;--type-font-family-serif: Gupter;--type-font-family-mono: IBM Plex Mono;--type-weights-300: 300;--type-weights-400: 400;--type-weights-500: 500;--type-weights-700: 700;--type-sizes-12: 12px;--type-sizes-14: 14px;--type-sizes-16: 16px;--type-sizes-18: 18px;--type-sizes-20: 20px;--type-sizes-22: 22px;--type-sizes-24: 24px;--type-sizes-28: 28px;--type-sizes-30: 30px;--type-sizes-32: 32px;--type-sizes-40: 40px;--type-sizes-42: 42px;--type-sizes-48-2: 48px;--type-line-heights-16: 16px;--type-line-heights-20: 20px;--type-line-heights-23: 23px;--type-line-heights-24: 24px;--type-line-heights-25: 25px;--type-line-heights-26: 26px;--type-line-heights-29: 29px;--type-line-heights-30: 30px;--type-line-heights-32: 32px;--type-line-heights-34: 34px;--type-line-heights-35: 35px;--type-line-heights-36: 36px;--type-line-heights-38: 38px;--type-line-heights-40: 40px;--type-line-heights-46: 46px;--type-line-heights-48: 48px;--type-line-heights-52: 52px;--type-line-heights-58: 58px;--type-line-heights-68: 68px;--type-line-heights-74: 74px;--type-line-heights-82: 82px;--type-paragraph-spacings-0: 0px;--type-paragraph-spacings-4: 4px;--type-paragraph-spacings-8: 8px;--type-paragraph-spacings-16: 16px;--type-sans-serif-xl-font-weight: 400;--type-sans-serif-xl-size: 32px;--type-sans-serif-xl-line-height: 46px;--type-sans-serif-xl-paragraph-spacing: 16px;--type-sans-serif-lg-font-weight: 400;--type-sans-serif-lg-size: 30px;--type-sans-serif-lg-line-height: 36px;--type-sans-serif-lg-paragraph-spacing: 16px;--type-sans-serif-md-font-weight: 400;--type-sans-serif-md-line-height: 30px;--type-sans-serif-md-paragraph-spacing: 16px;--type-sans-serif-md-size: 24px;--type-sans-serif-xs-font-weight: 700;--type-sans-serif-xs-line-height: 24px;--type-sans-serif-xs-paragraph-spacing: 0px;--type-sans-serif-xs-size: 18px;--type-sans-serif-sm-font-weight: 400;--type-sans-serif-sm-line-height: 32px;--type-sans-serif-sm-paragraph-spacing: 16px;--type-sans-serif-sm-size: 20px;--type-body-xl-font-weight: 400;--type-body-xl-size: 24px;--type-body-xl-line-height: 36px;--type-body-xl-paragraph-spacing: 0px;--type-body-sm-font-weight: 400;--type-body-sm-size: 14px;--type-body-sm-line-height: 20px;--type-body-sm-paragraph-spacing: 8px;--type-body-xs-font-weight: 400;--type-body-xs-size: 12px;--type-body-xs-line-height: 16px;--type-body-xs-paragraph-spacing: 0px;--type-body-md-font-weight: 400;--type-body-md-size: 16px;--type-body-md-line-height: 20px;--type-body-md-paragraph-spacing: 4px;--type-body-lg-font-weight: 400;--type-body-lg-size: 20px;--type-body-lg-line-height: 26px;--type-body-lg-paragraph-spacing: 16px;--type-body-lg-medium-font-weight: 500;--type-body-lg-medium-size: 20px;--type-body-lg-medium-line-height: 32px;--type-body-lg-medium-paragraph-spacing: 16px;--type-body-md-medium-font-weight: 500;--type-body-md-medium-size: 16px;--type-body-md-medium-line-height: 20px;--type-body-md-medium-paragraph-spacing: 4px;--type-body-sm-bold-font-weight: 700;--type-body-sm-bold-size: 14px;--type-body-sm-bold-line-height: 20px;--type-body-sm-bold-paragraph-spacing: 8px;--type-body-sm-medium-font-weight: 500;--type-body-sm-medium-size: 14px;--type-body-sm-medium-line-height: 20px;--type-body-sm-medium-paragraph-spacing: 8px;--type-serif-md-font-weight: 400;--type-serif-md-size: 32px;--type-serif-md-paragraph-spacing: 0px;--type-serif-md-line-height: 40px;--type-serif-sm-font-weight: 400;--type-serif-sm-size: 24px;--type-serif-sm-paragraph-spacing: 0px;--type-serif-sm-line-height: 26px;--type-serif-lg-font-weight: 400;--type-serif-lg-size: 48px;--type-serif-lg-paragraph-spacing: 0px;--type-serif-lg-line-height: 52px;--type-serif-xs-font-weight: 400;--type-serif-xs-size: 18px;--type-serif-xs-line-height: 24px;--type-serif-xs-paragraph-spacing: 0px;--type-serif-xl-font-weight: 400;--type-serif-xl-size: 48px;--type-serif-xl-paragraph-spacing: 0px;--type-serif-xl-line-height: 58px;--type-mono-md-font-weight: 400;--type-mono-md-size: 22px;--type-mono-md-line-height: 24px;--type-mono-md-paragraph-spacing: 0px;--type-mono-lg-font-weight: 400;--type-mono-lg-size: 40px;--type-mono-lg-line-height: 40px;--type-mono-lg-paragraph-spacing: 0px;--type-mono-sm-font-weight: 400;--type-mono-sm-size: 14px;--type-mono-sm-line-height: 24px;--type-mono-sm-paragraph-spacing: 0px;--spacing-xs-4: 4px;--spacing-xs-8: 8px;--spacing-xs-16: 16px;--spacing-sm-24: 24px;--spacing-sm-32: 32px;--spacing-md-40: 40px;--spacing-md-48: 48px;--spacing-lg-64: 64px;--spacing-lg-80: 80px;--spacing-xlg-104: 104px;--spacing-xlg-152: 152px;--spacing-xs-12: 12px;--spacing-page-section: 80px;--spacing-card-list-spacing: 48px;--spacing-text-section-spacing: 64px;--spacing-md-xs-headings: 40px;--corner-radius-radius-lg: 16px;--corner-radius-radius-sm: 4px;--corner-radius-radius-md: 8px;--corner-radius-radius-round: 104px}}@media(min-width: 568px)and (max-width: 1279px){:root{--token-mode: Rebrand;--dropshadow: 0 2px 4px 0 #22223340;--primary-brand: #0645b1;--error-dark: #b60000;--success-dark: #05b01c;--inactive-fill: #ebebee;--hover: #0c3b8d;--pressed: #082f75;--button-primary-fill-inactive: #ebebee;--button-primary-fill: #0645b1;--button-primary-text: #ffffff;--button-primary-fill-hover: #0c3b8d;--button-primary-fill-press: #082f75;--button-primary-icon: #ffffff;--button-primary-fill-inverse: #ffffff;--button-primary-text-inverse: #082f75;--button-primary-icon-inverse: #0645b1;--button-primary-fill-inverse-hover: #cddaef;--button-primary-stroke-inverse-pressed: #0645b1;--button-secondary-stroke-inactive: #b1b1ba;--button-secondary-fill: #eef2f9;--button-secondary-text: #082f75;--button-secondary-fill-press: #cddaef;--button-secondary-fill-inactive: #ebebee;--button-secondary-stroke: #cddaef;--button-secondary-stroke-hover: #386ac1;--button-secondary-stroke-press: #0645b1;--button-secondary-text-inactive: #b1b1ba;--button-secondary-icon: #082f75;--button-secondary-fill-hover: #e6ecf7;--button-secondary-stroke-inverse: #ffffff;--button-secondary-fill-inverse: rgba(255, 255, 255, 0);--button-secondary-icon-inverse: #ffffff;--button-secondary-icon-hover: #082f75;--button-secondary-icon-press: #082f75;--button-secondary-text-inverse: #ffffff;--button-secondary-text-hover: #082f75;--button-secondary-text-press: #082f75;--button-secondary-fill-inverse-hover: #043059;--button-xs-stroke: #141413;--button-xs-stroke-hover: #0c3b8d;--button-xs-stroke-press: #082f75;--button-xs-stroke-inactive: #ebebee;--button-xs-text: #141413;--button-xs-text-hover: #0c3b8d;--button-xs-text-press: #082f75;--button-xs-text-inactive: #91919e;--button-xs-icon: #141413;--button-xs-icon-hover: #0c3b8d;--button-xs-icon-press: #082f75;--button-xs-icon-inactive: #91919e;--button-xs-fill: #ffffff;--button-xs-fill-hover: #f4f7fc;--button-xs-fill-press: #eef2f9;--buttons-button-text-inactive: #91919e;--buttons-button-focus: #0645b1;--buttons-button-icon-inactive: #91919e;--buttons-small-buttons-corner-radius: 16px;--buttons-small-buttons-l-r-padding: 20px;--buttons-small-buttons-height: 48px;--buttons-small-buttons-gap: 8px;--buttons-small-buttons-icon-only-width: 48px;--buttons-small-buttons-icon-size: 20px;--buttons-small-buttons-stroke-default: 1px;--buttons-small-buttons-stroke-thick: 2px;--buttons-large-buttons-l-r-padding: 32px;--buttons-large-buttons-height: 64px;--buttons-large-buttons-icon-only-width: 64px;--buttons-large-buttons-icon-size: 20px;--buttons-large-buttons-gap: 8px;--buttons-large-buttons-corner-radius: 16px;--buttons-large-buttons-stroke-default: 1px;--buttons-large-buttons-stroke-thick: 2px;--buttons-extra-small-buttons-l-r-padding: 8px;--buttons-extra-small-buttons-height: 32px;--buttons-extra-small-buttons-icon-size: 16px;--buttons-extra-small-buttons-gap: 4px;--buttons-extra-small-buttons-corner-radius: 8px;--buttons-stroke-default: 1px;--buttons-stroke-thick: 2px;--background-beige: #f9f7f4;--error-light: #fff2f2;--text-placeholder: #6d6d7d;--stroke-dark: #141413;--stroke-light: #dddde2;--stroke-medium: #535366;--accent-green: #ccffd4;--accent-turquoise: #ccf7ff;--accent-yellow: #f7ffcc;--accent-peach: #ffd4cc;--accent-violet: #f7ccff;--accent-purple: #f4f7fc;--text-primary: #141413;--secondary-brand: #141413;--text-hover: #0c3b8d;--text-white: #ffffff;--text-link: #0645b1;--text-press: #082f75;--success-light: #f0f8f1;--background-light-blue: #f4f7fc;--background-white: #ffffff;--premium-dark: #877440;--premium-light: #f9f6ed;--stroke-white: #ffffff;--inactive-content: #b1b1ba;--annotate-light: #a35dff;--annotate-dark: #824acc;--grid: #eef2f9;--inactive-stroke: #ebebee;--shadow: rgba(34, 34, 51, 0.25);--text-inactive: #6d6d7d;--text-error: #b60000;--stroke-error: #b60000;--background-error: #fff2f2;--background-black: #141413;--icon-default: #141413;--icon-blue: #0645b1;--background-grey: #dddde2;--icon-grey: #b1b1ba;--text-focus: #082f75;--brand-colors-neutral-black: #141413;--brand-colors-neutral-900: #535366;--brand-colors-neutral-800: #6d6d7d;--brand-colors-neutral-700: #91919e;--brand-colors-neutral-600: #b1b1ba;--brand-colors-neutral-500: #c8c8cf;--brand-colors-neutral-400: #dddde2;--brand-colors-neutral-300: #ebebee;--brand-colors-neutral-200: #f8f8fb;--brand-colors-neutral-100: #fafafa;--brand-colors-neutral-white: #ffffff;--brand-colors-blue-900: #043059;--brand-colors-blue-800: #082f75;--brand-colors-blue-700: #0c3b8d;--brand-colors-blue-600: #0645b1;--brand-colors-blue-500: #386ac1;--brand-colors-blue-400: #cddaef;--brand-colors-blue-300: #e6ecf7;--brand-colors-blue-200: #eef2f9;--brand-colors-blue-100: #f4f7fc;--brand-colors-gold-500: #877440;--brand-colors-gold-400: #e9e3d4;--brand-colors-gold-300: #f2efe8;--brand-colors-gold-200: #f9f6ed;--brand-colors-gold-100: #f9f7f4;--brand-colors-error-900: #920000;--brand-colors-error-500: #b60000;--brand-colors-success-900: #035c0f;--brand-colors-green: #ccffd4;--brand-colors-turquoise: #ccf7ff;--brand-colors-yellow: #f7ffcc;--brand-colors-peach: #ffd4cc;--brand-colors-violet: #f7ccff;--brand-colors-error-100: #fff2f2;--brand-colors-success-500: #05b01c;--brand-colors-success-100: #f0f8f1;--text-secondary: #535366;--icon-white: #ffffff;--background-beige-darker: #f2efe8;--icon-dark-grey: #535366;--type-font-family-sans-serif: DM Sans;--type-font-family-serif: Gupter;--type-font-family-mono: IBM Plex Mono;--type-weights-300: 300;--type-weights-400: 400;--type-weights-500: 500;--type-weights-700: 700;--type-sizes-12: 12px;--type-sizes-14: 14px;--type-sizes-16: 16px;--type-sizes-18: 18px;--type-sizes-20: 20px;--type-sizes-22: 22px;--type-sizes-24: 24px;--type-sizes-28: 28px;--type-sizes-30: 30px;--type-sizes-32: 32px;--type-sizes-40: 40px;--type-sizes-42: 42px;--type-sizes-48-2: 48px;--type-line-heights-16: 16px;--type-line-heights-20: 20px;--type-line-heights-23: 23px;--type-line-heights-24: 24px;--type-line-heights-25: 25px;--type-line-heights-26: 26px;--type-line-heights-29: 29px;--type-line-heights-30: 30px;--type-line-heights-32: 32px;--type-line-heights-34: 34px;--type-line-heights-35: 35px;--type-line-heights-36: 36px;--type-line-heights-38: 38px;--type-line-heights-40: 40px;--type-line-heights-46: 46px;--type-line-heights-48: 48px;--type-line-heights-52: 52px;--type-line-heights-58: 58px;--type-line-heights-68: 68px;--type-line-heights-74: 74px;--type-line-heights-82: 82px;--type-paragraph-spacings-0: 0px;--type-paragraph-spacings-4: 4px;--type-paragraph-spacings-8: 8px;--type-paragraph-spacings-16: 16px;--type-sans-serif-xl-font-weight: 400;--type-sans-serif-xl-size: 42px;--type-sans-serif-xl-line-height: 46px;--type-sans-serif-xl-paragraph-spacing: 16px;--type-sans-serif-lg-font-weight: 400;--type-sans-serif-lg-size: 32px;--type-sans-serif-lg-line-height: 36px;--type-sans-serif-lg-paragraph-spacing: 16px;--type-sans-serif-md-font-weight: 400;--type-sans-serif-md-line-height: 34px;--type-sans-serif-md-paragraph-spacing: 16px;--type-sans-serif-md-size: 28px;--type-sans-serif-xs-font-weight: 700;--type-sans-serif-xs-line-height: 25px;--type-sans-serif-xs-paragraph-spacing: 0px;--type-sans-serif-xs-size: 20px;--type-sans-serif-sm-font-weight: 400;--type-sans-serif-sm-line-height: 30px;--type-sans-serif-sm-paragraph-spacing: 16px;--type-sans-serif-sm-size: 24px;--type-body-xl-font-weight: 400;--type-body-xl-size: 24px;--type-body-xl-line-height: 36px;--type-body-xl-paragraph-spacing: 0px;--type-body-sm-font-weight: 400;--type-body-sm-size: 14px;--type-body-sm-line-height: 20px;--type-body-sm-paragraph-spacing: 8px;--type-body-xs-font-weight: 400;--type-body-xs-size: 12px;--type-body-xs-line-height: 16px;--type-body-xs-paragraph-spacing: 0px;--type-body-md-font-weight: 400;--type-body-md-size: 16px;--type-body-md-line-height: 20px;--type-body-md-paragraph-spacing: 4px;--type-body-lg-font-weight: 400;--type-body-lg-size: 20px;--type-body-lg-line-height: 26px;--type-body-lg-paragraph-spacing: 16px;--type-body-lg-medium-font-weight: 500;--type-body-lg-medium-size: 20px;--type-body-lg-medium-line-height: 32px;--type-body-lg-medium-paragraph-spacing: 16px;--type-body-md-medium-font-weight: 500;--type-body-md-medium-size: 16px;--type-body-md-medium-line-height: 20px;--type-body-md-medium-paragraph-spacing: 4px;--type-body-sm-bold-font-weight: 700;--type-body-sm-bold-size: 14px;--type-body-sm-bold-line-height: 20px;--type-body-sm-bold-paragraph-spacing: 8px;--type-body-sm-medium-font-weight: 500;--type-body-sm-medium-size: 14px;--type-body-sm-medium-line-height: 20px;--type-body-sm-medium-paragraph-spacing: 8px;--type-serif-md-font-weight: 400;--type-serif-md-size: 40px;--type-serif-md-paragraph-spacing: 0px;--type-serif-md-line-height: 48px;--type-serif-sm-font-weight: 400;--type-serif-sm-size: 28px;--type-serif-sm-paragraph-spacing: 0px;--type-serif-sm-line-height: 32px;--type-serif-lg-font-weight: 400;--type-serif-lg-size: 58px;--type-serif-lg-paragraph-spacing: 0px;--type-serif-lg-line-height: 68px;--type-serif-xs-font-weight: 400;--type-serif-xs-size: 18px;--type-serif-xs-line-height: 24px;--type-serif-xs-paragraph-spacing: 0px;--type-serif-xl-font-weight: 400;--type-serif-xl-size: 74px;--type-serif-xl-paragraph-spacing: 0px;--type-serif-xl-line-height: 82px;--type-mono-md-font-weight: 400;--type-mono-md-size: 22px;--type-mono-md-line-height: 24px;--type-mono-md-paragraph-spacing: 0px;--type-mono-lg-font-weight: 400;--type-mono-lg-size: 40px;--type-mono-lg-line-height: 40px;--type-mono-lg-paragraph-spacing: 0px;--type-mono-sm-font-weight: 400;--type-mono-sm-size: 14px;--type-mono-sm-line-height: 24px;--type-mono-sm-paragraph-spacing: 0px;--spacing-xs-4: 4px;--spacing-xs-8: 8px;--spacing-xs-16: 16px;--spacing-sm-24: 24px;--spacing-sm-32: 32px;--spacing-md-40: 40px;--spacing-md-48: 48px;--spacing-lg-64: 64px;--spacing-lg-80: 80px;--spacing-xlg-104: 104px;--spacing-xlg-152: 152px;--spacing-xs-12: 12px;--spacing-page-section: 104px;--spacing-card-list-spacing: 48px;--spacing-text-section-spacing: 80px;--spacing-md-xs-headings: 40px;--corner-radius-radius-lg: 16px;--corner-radius-radius-sm: 4px;--corner-radius-radius-md: 8px;--corner-radius-radius-round: 104px}}@media(min-width: 1280px){:root{--token-mode: Rebrand;--dropshadow: 0 2px 4px 0 #22223340;--primary-brand: #0645b1;--error-dark: #b60000;--success-dark: #05b01c;--inactive-fill: #ebebee;--hover: #0c3b8d;--pressed: #082f75;--button-primary-fill-inactive: #ebebee;--button-primary-fill: #0645b1;--button-primary-text: #ffffff;--button-primary-fill-hover: #0c3b8d;--button-primary-fill-press: #082f75;--button-primary-icon: #ffffff;--button-primary-fill-inverse: #ffffff;--button-primary-text-inverse: #082f75;--button-primary-icon-inverse: #0645b1;--button-primary-fill-inverse-hover: #cddaef;--button-primary-stroke-inverse-pressed: #0645b1;--button-secondary-stroke-inactive: #b1b1ba;--button-secondary-fill: #eef2f9;--button-secondary-text: #082f75;--button-secondary-fill-press: #cddaef;--button-secondary-fill-inactive: #ebebee;--button-secondary-stroke: #cddaef;--button-secondary-stroke-hover: #386ac1;--button-secondary-stroke-press: #0645b1;--button-secondary-text-inactive: #b1b1ba;--button-secondary-icon: #082f75;--button-secondary-fill-hover: #e6ecf7;--button-secondary-stroke-inverse: #ffffff;--button-secondary-fill-inverse: rgba(255, 255, 255, 0);--button-secondary-icon-inverse: #ffffff;--button-secondary-icon-hover: #082f75;--button-secondary-icon-press: #082f75;--button-secondary-text-inverse: #ffffff;--button-secondary-text-hover: #082f75;--button-secondary-text-press: #082f75;--button-secondary-fill-inverse-hover: #043059;--button-xs-stroke: #141413;--button-xs-stroke-hover: #0c3b8d;--button-xs-stroke-press: #082f75;--button-xs-stroke-inactive: #ebebee;--button-xs-text: #141413;--button-xs-text-hover: #0c3b8d;--button-xs-text-press: #082f75;--button-xs-text-inactive: #91919e;--button-xs-icon: #141413;--button-xs-icon-hover: #0c3b8d;--button-xs-icon-press: #082f75;--button-xs-icon-inactive: #91919e;--button-xs-fill: #ffffff;--button-xs-fill-hover: #f4f7fc;--button-xs-fill-press: #eef2f9;--buttons-button-text-inactive: #91919e;--buttons-button-focus: #0645b1;--buttons-button-icon-inactive: #91919e;--buttons-small-buttons-corner-radius: 16px;--buttons-small-buttons-l-r-padding: 20px;--buttons-small-buttons-height: 48px;--buttons-small-buttons-gap: 8px;--buttons-small-buttons-icon-only-width: 48px;--buttons-small-buttons-icon-size: 20px;--buttons-small-buttons-stroke-default: 1px;--buttons-small-buttons-stroke-thick: 2px;--buttons-large-buttons-l-r-padding: 32px;--buttons-large-buttons-height: 64px;--buttons-large-buttons-icon-only-width: 64px;--buttons-large-buttons-icon-size: 20px;--buttons-large-buttons-gap: 8px;--buttons-large-buttons-corner-radius: 16px;--buttons-large-buttons-stroke-default: 1px;--buttons-large-buttons-stroke-thick: 2px;--buttons-extra-small-buttons-l-r-padding: 8px;--buttons-extra-small-buttons-height: 32px;--buttons-extra-small-buttons-icon-size: 16px;--buttons-extra-small-buttons-gap: 4px;--buttons-extra-small-buttons-corner-radius: 8px;--buttons-stroke-default: 1px;--buttons-stroke-thick: 2px;--background-beige: #f9f7f4;--error-light: #fff2f2;--text-placeholder: #6d6d7d;--stroke-dark: #141413;--stroke-light: #dddde2;--stroke-medium: #535366;--accent-green: #ccffd4;--accent-turquoise: #ccf7ff;--accent-yellow: #f7ffcc;--accent-peach: #ffd4cc;--accent-violet: #f7ccff;--accent-purple: #f4f7fc;--text-primary: #141413;--secondary-brand: #141413;--text-hover: #0c3b8d;--text-white: #ffffff;--text-link: #0645b1;--text-press: #082f75;--success-light: #f0f8f1;--background-light-blue: #f4f7fc;--background-white: #ffffff;--premium-dark: #877440;--premium-light: #f9f6ed;--stroke-white: #ffffff;--inactive-content: #b1b1ba;--annotate-light: #a35dff;--annotate-dark: #824acc;--grid: #eef2f9;--inactive-stroke: #ebebee;--shadow: rgba(34, 34, 51, 0.25);--text-inactive: #6d6d7d;--text-error: #b60000;--stroke-error: #b60000;--background-error: #fff2f2;--background-black: #141413;--icon-default: #141413;--icon-blue: #0645b1;--background-grey: #dddde2;--icon-grey: #b1b1ba;--text-focus: #082f75;--brand-colors-neutral-black: #141413;--brand-colors-neutral-900: #535366;--brand-colors-neutral-800: #6d6d7d;--brand-colors-neutral-700: #91919e;--brand-colors-neutral-600: #b1b1ba;--brand-colors-neutral-500: #c8c8cf;--brand-colors-neutral-400: #dddde2;--brand-colors-neutral-300: #ebebee;--brand-colors-neutral-200: #f8f8fb;--brand-colors-neutral-100: #fafafa;--brand-colors-neutral-white: #ffffff;--brand-colors-blue-900: #043059;--brand-colors-blue-800: #082f75;--brand-colors-blue-700: #0c3b8d;--brand-colors-blue-600: #0645b1;--brand-colors-blue-500: #386ac1;--brand-colors-blue-400: #cddaef;--brand-colors-blue-300: #e6ecf7;--brand-colors-blue-200: #eef2f9;--brand-colors-blue-100: #f4f7fc;--brand-colors-gold-500: #877440;--brand-colors-gold-400: #e9e3d4;--brand-colors-gold-300: #f2efe8;--brand-colors-gold-200: #f9f6ed;--brand-colors-gold-100: #f9f7f4;--brand-colors-error-900: #920000;--brand-colors-error-500: #b60000;--brand-colors-success-900: #035c0f;--brand-colors-green: #ccffd4;--brand-colors-turquoise: #ccf7ff;--brand-colors-yellow: #f7ffcc;--brand-colors-peach: #ffd4cc;--brand-colors-violet: #f7ccff;--brand-colors-error-100: #fff2f2;--brand-colors-success-500: #05b01c;--brand-colors-success-100: #f0f8f1;--text-secondary: #535366;--icon-white: #ffffff;--background-beige-darker: #f2efe8;--icon-dark-grey: #535366;--type-font-family-sans-serif: DM Sans;--type-font-family-serif: Gupter;--type-font-family-mono: IBM Plex Mono;--type-weights-300: 300;--type-weights-400: 400;--type-weights-500: 500;--type-weights-700: 700;--type-sizes-12: 12px;--type-sizes-14: 14px;--type-sizes-16: 16px;--type-sizes-18: 18px;--type-sizes-20: 20px;--type-sizes-22: 22px;--type-sizes-24: 24px;--type-sizes-28: 28px;--type-sizes-30: 30px;--type-sizes-32: 32px;--type-sizes-40: 40px;--type-sizes-42: 42px;--type-sizes-48-2: 48px;--type-line-heights-16: 16px;--type-line-heights-20: 20px;--type-line-heights-23: 23px;--type-line-heights-24: 24px;--type-line-heights-25: 25px;--type-line-heights-26: 26px;--type-line-heights-29: 29px;--type-line-heights-30: 30px;--type-line-heights-32: 32px;--type-line-heights-34: 34px;--type-line-heights-35: 35px;--type-line-heights-36: 36px;--type-line-heights-38: 38px;--type-line-heights-40: 40px;--type-line-heights-46: 46px;--type-line-heights-48: 48px;--type-line-heights-52: 52px;--type-line-heights-58: 58px;--type-line-heights-68: 68px;--type-line-heights-74: 74px;--type-line-heights-82: 82px;--type-paragraph-spacings-0: 0px;--type-paragraph-spacings-4: 4px;--type-paragraph-spacings-8: 8px;--type-paragraph-spacings-16: 16px;--type-sans-serif-xl-font-weight: 400;--type-sans-serif-xl-size: 42px;--type-sans-serif-xl-line-height: 46px;--type-sans-serif-xl-paragraph-spacing: 16px;--type-sans-serif-lg-font-weight: 400;--type-sans-serif-lg-size: 32px;--type-sans-serif-lg-line-height: 38px;--type-sans-serif-lg-paragraph-spacing: 16px;--type-sans-serif-md-font-weight: 400;--type-sans-serif-md-line-height: 34px;--type-sans-serif-md-paragraph-spacing: 16px;--type-sans-serif-md-size: 28px;--type-sans-serif-xs-font-weight: 700;--type-sans-serif-xs-line-height: 25px;--type-sans-serif-xs-paragraph-spacing: 0px;--type-sans-serif-xs-size: 20px;--type-sans-serif-sm-font-weight: 400;--type-sans-serif-sm-line-height: 30px;--type-sans-serif-sm-paragraph-spacing: 16px;--type-sans-serif-sm-size: 24px;--type-body-xl-font-weight: 400;--type-body-xl-size: 24px;--type-body-xl-line-height: 36px;--type-body-xl-paragraph-spacing: 0px;--type-body-sm-font-weight: 400;--type-body-sm-size: 14px;--type-body-sm-line-height: 20px;--type-body-sm-paragraph-spacing: 8px;--type-body-xs-font-weight: 400;--type-body-xs-size: 12px;--type-body-xs-line-height: 16px;--type-body-xs-paragraph-spacing: 0px;--type-body-md-font-weight: 400;--type-body-md-size: 16px;--type-body-md-line-height: 20px;--type-body-md-paragraph-spacing: 4px;--type-body-lg-font-weight: 400;--type-body-lg-size: 20px;--type-body-lg-line-height: 26px;--type-body-lg-paragraph-spacing: 16px;--type-body-lg-medium-font-weight: 500;--type-body-lg-medium-size: 20px;--type-body-lg-medium-line-height: 32px;--type-body-lg-medium-paragraph-spacing: 16px;--type-body-md-medium-font-weight: 500;--type-body-md-medium-size: 16px;--type-body-md-medium-line-height: 20px;--type-body-md-medium-paragraph-spacing: 4px;--type-body-sm-bold-font-weight: 700;--type-body-sm-bold-size: 14px;--type-body-sm-bold-line-height: 20px;--type-body-sm-bold-paragraph-spacing: 8px;--type-body-sm-medium-font-weight: 500;--type-body-sm-medium-size: 14px;--type-body-sm-medium-line-height: 20px;--type-body-sm-medium-paragraph-spacing: 8px;--type-serif-md-font-weight: 400;--type-serif-md-size: 40px;--type-serif-md-paragraph-spacing: 0px;--type-serif-md-line-height: 48px;--type-serif-sm-font-weight: 400;--type-serif-sm-size: 28px;--type-serif-sm-paragraph-spacing: 0px;--type-serif-sm-line-height: 32px;--type-serif-lg-font-weight: 400;--type-serif-lg-size: 58px;--type-serif-lg-paragraph-spacing: 0px;--type-serif-lg-line-height: 68px;--type-serif-xs-font-weight: 400;--type-serif-xs-size: 18px;--type-serif-xs-line-height: 24px;--type-serif-xs-paragraph-spacing: 0px;--type-serif-xl-font-weight: 400;--type-serif-xl-size: 74px;--type-serif-xl-paragraph-spacing: 0px;--type-serif-xl-line-height: 82px;--type-mono-md-font-weight: 400;--type-mono-md-size: 22px;--type-mono-md-line-height: 24px;--type-mono-md-paragraph-spacing: 0px;--type-mono-lg-font-weight: 400;--type-mono-lg-size: 40px;--type-mono-lg-line-height: 40px;--type-mono-lg-paragraph-spacing: 0px;--type-mono-sm-font-weight: 400;--type-mono-sm-size: 14px;--type-mono-sm-line-height: 24px;--type-mono-sm-paragraph-spacing: 0px;--spacing-xs-4: 4px;--spacing-xs-8: 8px;--spacing-xs-16: 16px;--spacing-sm-24: 24px;--spacing-sm-32: 32px;--spacing-md-40: 40px;--spacing-md-48: 48px;--spacing-lg-64: 64px;--spacing-lg-80: 80px;--spacing-xlg-104: 104px;--spacing-xlg-152: 152px;--spacing-xs-12: 12px;--spacing-page-section: 152px;--spacing-card-list-spacing: 48px;--spacing-text-section-spacing: 80px;--spacing-md-xs-headings: 40px;--corner-radius-radius-lg: 16px;--corner-radius-radius-sm: 4px;--corner-radius-radius-md: 8px;--corner-radius-radius-round: 104px}}</style><link rel="stylesheet" media="all" href="//a.academia-assets.com/assets/single_work_page/loswp-fd2fcde21889491abfafcac2e33d795c8d15f5c18207be857e53e09b77f94215.css" /><link rel="stylesheet" media="all" href="//a.academia-assets.com/assets/design_system/body-170d1319f0e354621e81ca17054bb147da2856ec0702fe440a99af314a6338c5.css" /><link rel="stylesheet" media="all" href="//a.academia-assets.com/assets/design_system/button-bfbac2a470372e2f3a6661a65fa7ff0a0fbf7aa32534d9a831d683d2a6f9e01b.css" /><link rel="stylesheet" media="all" href="//a.academia-assets.com/assets/design_system/heading-95367dc03b794f6737f30123738a886cf53b7a65cdef98a922a98591d60063e3.css" /><link rel="stylesheet" media="all" href="//a.academia-assets.com/assets/design_system/text_button-d1941ab08e91e29ee143084c4749da4aaffa350a2ac6eec2306b1d7a352d911a.css" /><link crossorigin="" href="https://fonts.gstatic.com/" rel="preconnect" /><link href="https://fonts.googleapis.com/css2?family=DM+Sans:ital,opsz,wght@0,9..40,100..1000;1,9..40,100..1000&family=Gupter:wght@400;500;700&family=IBM+Plex+Mono:wght@300;400&family=Material+Symbols+Outlined:opsz,wght,FILL,GRAD@20,400,0,0&display=swap" rel="stylesheet" /> </head> <body> <div id='react-modal'></div> <div class="js-upgrade-ie-banner" style="display: none; text-align: center; padding: 8px 0; background-color: #ebe480;"><p style="color: #000; font-size: 12px; margin: 0 0 4px;">Academia.edu no longer supports Internet Explorer.</p><p style="color: #000; font-size: 12px; margin: 0;">To browse Academia.edu and the wider internet faster and more securely, please take a few seconds to <a href="https://www.academia.edu/upgrade-browser">upgrade your browser</a>.</p></div><script>// Show this banner for all versions of IE if (!!window.MSInputMethodContext || /(MSIE)/.test(navigator.userAgent)) { document.querySelector('.js-upgrade-ie-banner').style.display = 'block'; }</script> <div class="bootstrap login"><div class="modal fade login-modal" id="login-modal"><div class="login-modal-dialog modal-dialog"><div class="modal-content"><div class="modal-header"><button class="close close" data-dismiss="modal" type="button"><span aria-hidden="true">×</span><span class="sr-only">Close</span></button><h4 class="modal-title text-center"><strong>Log In</strong></h4></div><div class="modal-body"><div class="row"><div class="col-xs-10 col-xs-offset-1"><button class="btn btn-fb btn-lg btn-block btn-v-center-content" id="login-facebook-oauth-button"><svg style="float: left; width: 19px; line-height: 1em; margin-right: .3em;" aria-hidden="true" focusable="false" data-prefix="fab" data-icon="facebook-square" class="svg-inline--fa fa-facebook-square fa-w-14" role="img" xmlns="http://www.w3.org/2000/svg" viewBox="0 0 448 512"><path fill="currentColor" d="M400 32H48A48 48 0 0 0 0 80v352a48 48 0 0 0 48 48h137.25V327.69h-63V256h63v-54.64c0-62.15 37-96.48 93.67-96.48 27.14 0 55.52 4.84 55.52 4.84v61h-31.27c-30.81 0-40.42 19.12-40.42 38.73V256h68.78l-11 71.69h-57.78V480H400a48 48 0 0 0 48-48V80a48 48 0 0 0-48-48z"></path></svg><small><strong>Log in</strong> with <strong>Facebook</strong></small></button><br /><button class="btn btn-google btn-lg btn-block btn-v-center-content" id="login-google-oauth-button"><svg style="float: left; width: 22px; line-height: 1em; margin-right: .3em;" aria-hidden="true" focusable="false" data-prefix="fab" data-icon="google-plus" class="svg-inline--fa fa-google-plus fa-w-16" role="img" xmlns="http://www.w3.org/2000/svg" viewBox="0 0 512 512"><path fill="currentColor" d="M256,8C119.1,8,8,119.1,8,256S119.1,504,256,504,504,392.9,504,256,392.9,8,256,8ZM185.3,380a124,124,0,0,1,0-248c31.3,0,60.1,11,83,32.3l-33.6,32.6c-13.2-12.9-31.3-19.1-49.4-19.1-42.9,0-77.2,35.5-77.2,78.1S142.3,334,185.3,334c32.6,0,64.9-19.1,70.1-53.3H185.3V238.1H302.2a109.2,109.2,0,0,1,1.9,20.7c0,70.8-47.5,121.2-118.8,121.2ZM415.5,273.8v35.5H380V273.8H344.5V238.3H380V202.8h35.5v35.5h35.2v35.5Z"></path></svg><small><strong>Log in</strong> with <strong>Google</strong></small></button><br /><style type="text/css">.sign-in-with-apple-button { width: 100%; height: 52px; border-radius: 3px; border: 1px solid black; cursor: pointer; } .sign-in-with-apple-button > div { margin: 0 auto; / This centers the Apple-rendered button horizontally }</style><script src="https://appleid.cdn-apple.com/appleauth/static/jsapi/appleid/1/en_US/appleid.auth.js" type="text/javascript"></script><div class="sign-in-with-apple-button" data-border="false" data-color="white" id="appleid-signin"><span   ="Sign Up with Apple" class="u-fs11"></span></div><script>AppleID.auth.init({ clientId: 'edu.academia.applesignon', scope: 'name email', redirectURI: 'https://www.academia.edu/sessions', state: "803822032a43a352ebd211a29ba9beb051631f21510b1a00b8eca732a81ab686", });</script><script>// Hacky way of checking if on fast loswp if (window.loswp == null) { (function() { const Google = window?.Aedu?.Auth?.OauthButton?.Login?.Google; const Facebook = window?.Aedu?.Auth?.OauthButton?.Login?.Facebook; if (Google) { new Google({ el: '#login-google-oauth-button', rememberMeCheckboxId: 'remember_me', track: null }); } if (Facebook) { new Facebook({ el: '#login-facebook-oauth-button', rememberMeCheckboxId: 'remember_me', track: null }); } })(); }</script></div></div></div><div class="modal-body"><div class="row"><div class="col-xs-10 col-xs-offset-1"><div class="hr-heading login-hr-heading"><span class="hr-heading-text">or</span></div></div></div></div><div class="modal-body"><div class="row"><div class="col-xs-10 col-xs-offset-1"><form class="js-login-form" action="https://www.academia.edu/sessions" accept-charset="UTF-8" method="post"><input type="hidden" name="authenticity_token" value="pTImN2WI2quz_DXVc4b9XP2-QTo6Szh-A80mKslxRpAR2xcEbSRl7wXaqxnMvziA0q0LZsCEY7b57dAzb77dpg" autocomplete="off" /><div class="form-group"><label class="control-label" for="login-modal-email-input" style="font-size: 14px;">Email</label><input class="form-control" id="login-modal-email-input" name="login" type="email" /></div><div class="form-group"><label class="control-label" for="login-modal-password-input" style="font-size: 14px;">Password</label><input class="form-control" id="login-modal-password-input" name="password" type="password" /></div><input type="hidden" name="post_login_redirect_url" id="post_login_redirect_url" value="https://www.academia.edu/33009414/metabolites_Unraveling_Biochemical_Pathways_Affected_by_M_itochondrial_Dysfunctions_Using_M_etabolomic_Approaches" autocomplete="off" /><div class="checkbox"><label><input type="checkbox" name="remember_me" id="remember_me" value="1" checked="checked" /><small style="font-size: 12px; margin-top: 2px; display: inline-block;">Remember me on this computer</small></label></div><br><input type="submit" name="commit" value="Log In" class="btn btn-primary btn-block btn-lg js-login-submit" data-disable-with="Log In" /></br></form><script>typeof window?.Aedu?.recaptchaManagedForm === 'function' && window.Aedu.recaptchaManagedForm( document.querySelector('.js-login-form'), document.querySelector('.js-login-submit') );</script><small style="font-size: 12px;"><br />or <a data-target="#login-modal-reset-password-container" data-toggle="collapse" href="javascript:void(0)">reset password</a></small><div class="collapse" id="login-modal-reset-password-container"><br /><div class="well margin-0x"><form class="js-password-reset-form" action="https://www.academia.edu/reset_password" accept-charset="UTF-8" method="post"><input type="hidden" name="authenticity_token" value="9ew3BggsPsAoknKIy8Wnt0diTr7z8M4m_QZQsWyOx4pBBQY1AICBhJ607ER0_GJraHEE4gk_le4HJqaoykFcvA" autocomplete="off" /><p>Enter the email address you signed up with and we'll email you a reset link.</p><div class="form-group"><input class="form-control" name="email" type="email" /></div><input class="btn btn-primary btn-block g-recaptcha js-password-reset-submit" data-sitekey="6Lf3KHUUAAAAACggoMpmGJdQDtiyrjVlvGJ6BbAj" type="submit" value="Email me a link" /></form></div></div><script> require.config({ waitSeconds: 90 })(["https://a.academia-assets.com/assets/collapse-45805421cf446ca5adf7aaa1935b08a3a8d1d9a6cc5d91a62a2a3a00b20b3e6a.js"], function() { // from javascript_helper.rb $("#login-modal-reset-password-container").on("shown.bs.collapse", function() { $(this).find("input[type=email]").focus(); }); }); </script> </div></div></div><div class="modal-footer"><div class="text-center"><small style="font-size: 12px;">Need an account? <a rel="nofollow" href="https://www.academia.edu/signup">Click here to sign up</a></small></div></div></div></div></div></div><script>// If we are on subdomain or non-bootstrapped page, redirect to login page instead of showing modal (function(){ if (typeof $ === 'undefined') return; var host = window.location.hostname; if ((host === $domain || host === "www."+$domain) && (typeof $().modal === 'function')) { $("#nav_log_in").click(function(e) { // Don't follow the link and open the modal e.preventDefault(); $("#login-modal").on('shown.bs.modal', function() { $(this).find("#login-modal-email-input").focus() }).modal('show'); }); } })()</script> <div id="fb-root"></div><script>window.fbAsyncInit = function() { FB.init({ appId: "2369844204", version: "v8.0", status: true, cookie: true, xfbml: true }); // Additional initialization code. if (window.InitFacebook) { // facebook.ts already loaded, set it up. window.InitFacebook(); } else { // Set a flag for facebook.ts to find when it loads. window.academiaAuthReadyFacebook = true; } };</script> <div id="google-root"></div><script>window.loadGoogle = function() { if (window.InitGoogle) { // google.ts already loaded, set it up. window.InitGoogle("331998490334-rsn3chp12mbkiqhl6e7lu2q0mlbu0f1b"); } else { // Set a flag for google.ts to use when it loads. window.GoogleClientID = "331998490334-rsn3chp12mbkiqhl6e7lu2q0mlbu0f1b"; } };</script> <div class="header--container" id="main-header-container"><div class="header--inner-container header--inner-container-ds2"><div class="header-ds2--left-wrapper"><div class="header-ds2--left-wrapper-inner"><a data-main-header-link-target="logo_home" href="https://www.academia.edu/"><img class="hide-on-desktop-redesign" style="height: 24px; width: 24px;" alt="Academia.edu" src="//a.academia-assets.com/images/academia-logo-redesign-2015-A.svg" width="24" height="24" /><img width="145.2" height="18" class="hide-on-mobile-redesign" style="height: 24px;" alt="Academia.edu" src="//a.academia-assets.com/images/academia-logo-redesign-2015.svg" /></a><div class="header--search-container header--search-container-ds2"><form class="js-SiteSearch-form select2-no-default-pills" action="https://www.academia.edu/search" accept-charset="UTF-8" method="get"><svg style="width: 14px; height: 14px;" aria-hidden="true" focusable="false" data-prefix="fas" data-icon="search" class="header--search-icon svg-inline--fa fa-search fa-w-16" role="img" xmlns="http://www.w3.org/2000/svg" viewBox="0 0 512 512"><path fill="currentColor" d="M505 442.7L405.3 343c-4.5-4.5-10.6-7-17-7H372c27.6-35.3 44-79.7 44-128C416 93.1 322.9 0 208 0S0 93.1 0 208s93.1 208 208 208c48.3 0 92.7-16.4 128-44v16.3c0 6.4 2.5 12.5 7 17l99.7 99.7c9.4 9.4 24.6 9.4 33.9 0l28.3-28.3c9.4-9.4 9.4-24.6.1-34zM208 336c-70.7 0-128-57.2-128-128 0-70.7 57.2-128 128-128 70.7 0 128 57.2 128 128 0 70.7-57.2 128-128 128z"></path></svg><input class="header--search-input header--search-input-ds2 js-SiteSearch-form-input" data-main-header-click-target="search_input" name="q" placeholder="Search" type="text" /></form></div></div></div><nav class="header--nav-buttons header--nav-buttons-ds2 js-main-nav"><button class="ds2-5-button ds2-5-button--secondary js-header-login-url header-button-ds2 header-login-ds2 hide-on-mobile-redesign react-login-modal-opener" data-signup-modal="{"location":"login-button--header"}" rel="nofollow">Log In</button><button class="ds2-5-button ds2-5-button--secondary header-button-ds2 hide-on-mobile-redesign react-login-modal-opener" data-signup-modal="{"location":"signup-button--header"}" rel="nofollow">Sign Up</button><button class="header--hamburger-button header--hamburger-button-ds2 hide-on-desktop-redesign js-header-hamburger-button"><div class="icon-bar"></div><div class="icon-bar" style="margin-top: 4px;"></div><div class="icon-bar" style="margin-top: 4px;"></div></button></nav></div><ul class="header--dropdown-container js-header-dropdown"><li class="header--dropdown-row"><a class="header--dropdown-link" href="https://www.academia.edu/login" rel="nofollow">Log In</a></li><li class="header--dropdown-row"><a class="header--dropdown-link" href="https://www.academia.edu/signup" rel="nofollow">Sign Up</a></li><li class="header--dropdown-row js-header-dropdown-expand-button"><button class="header--dropdown-button">more<svg aria-hidden="true" focusable="false" data-prefix="fas" data-icon="caret-down" class="header--dropdown-button-icon svg-inline--fa fa-caret-down fa-w-10" role="img" xmlns="http://www.w3.org/2000/svg" viewBox="0 0 320 512"><path fill="currentColor" d="M31.3 192h257.3c17.8 0 26.7 21.5 14.1 34.1L174.1 354.8c-7.8 7.8-20.5 7.8-28.3 0L17.2 226.1C4.6 213.5 13.5 192 31.3 192z"></path></svg></button></li><li><ul class="header--expanded-dropdown-container"><li class="header--dropdown-row"><a class="header--dropdown-link" href="https://www.academia.edu/about">About</a></li><li class="header--dropdown-row"><a class="header--dropdown-link" href="https://www.academia.edu/press">Press</a></li><li class="header--dropdown-row"><a class="header--dropdown-link" href="https://www.academia.edu/documents">Papers</a></li><li class="header--dropdown-row"><a class="header--dropdown-link" href="https://www.academia.edu/terms">Terms</a></li><li class="header--dropdown-row"><a class="header--dropdown-link" href="https://www.academia.edu/privacy">Privacy</a></li><li class="header--dropdown-row"><a class="header--dropdown-link" href="https://www.academia.edu/copyright">Copyright</a></li><li class="header--dropdown-row"><a class="header--dropdown-link" href="https://www.academia.edu/hiring"><svg aria-hidden="true" focusable="false" data-prefix="fas" data-icon="briefcase" class="header--dropdown-row-icon svg-inline--fa fa-briefcase fa-w-16" role="img" xmlns="http://www.w3.org/2000/svg" viewBox="0 0 512 512"><path fill="currentColor" d="M320 336c0 8.84-7.16 16-16 16h-96c-8.84 0-16-7.16-16-16v-48H0v144c0 25.6 22.4 48 48 48h416c25.6 0 48-22.4 48-48V288H320v48zm144-208h-80V80c0-25.6-22.4-48-48-48H176c-25.6 0-48 22.4-48 48v48H48c-25.6 0-48 22.4-48 48v80h512v-80c0-25.6-22.4-48-48-48zm-144 0H192V96h128v32z"></path></svg>We're Hiring!</a></li><li class="header--dropdown-row"><a class="header--dropdown-link" href="https://support.academia.edu/hc/en-us"><svg aria-hidden="true" focusable="false" data-prefix="fas" data-icon="question-circle" class="header--dropdown-row-icon svg-inline--fa fa-question-circle fa-w-16" role="img" xmlns="http://www.w3.org/2000/svg" viewBox="0 0 512 512"><path fill="currentColor" d="M504 256c0 136.997-111.043 248-248 248S8 392.997 8 256C8 119.083 119.043 8 256 8s248 111.083 248 248zM262.655 90c-54.497 0-89.255 22.957-116.549 63.758-3.536 5.286-2.353 12.415 2.715 16.258l34.699 26.31c5.205 3.947 12.621 3.008 16.665-2.122 17.864-22.658 30.113-35.797 57.303-35.797 20.429 0 45.698 13.148 45.698 32.958 0 14.976-12.363 22.667-32.534 33.976C247.128 238.528 216 254.941 216 296v4c0 6.627 5.373 12 12 12h56c6.627 0 12-5.373 12-12v-1.333c0-28.462 83.186-29.647 83.186-106.667 0-58.002-60.165-102-116.531-102zM256 338c-25.365 0-46 20.635-46 46 0 25.364 20.635 46 46 46s46-20.636 46-46c0-25.365-20.635-46-46-46z"></path></svg>Help Center</a></li><li class="header--dropdown-row js-header-dropdown-collapse-button"><button class="header--dropdown-button">less<svg aria-hidden="true" focusable="false" data-prefix="fas" data-icon="caret-up" class="header--dropdown-button-icon svg-inline--fa fa-caret-up fa-w-10" role="img" xmlns="http://www.w3.org/2000/svg" viewBox="0 0 320 512"><path fill="currentColor" d="M288.662 352H31.338c-17.818 0-26.741-21.543-14.142-34.142l128.662-128.662c7.81-7.81 20.474-7.81 28.284 0l128.662 128.662c12.6 12.599 3.676 34.142-14.142 34.142z"></path></svg></button></li></ul></li></ul></div> <script src="//a.academia-assets.com/assets/webpack_bundles/fast_loswp-bundle-ea46870ff31fbdadd62b2119244184b91d92cb17fe88e9f620fdaf9921239082.js" defer="defer"></script><script>window.loswp = {}; window.loswp.author = 44230520; window.loswp.bulkDownloadFilterCounts = {}; window.loswp.hasDownloadableAttachment = true; window.loswp.hasViewableAttachments = true; // TODO: just use routes for this window.loswp.loginUrl = "https://www.academia.edu/login?post_login_redirect_url=https%3A%2F%2Fwww.academia.edu%2F33009414%2Fmetabolites_Unraveling_Biochemical_Pathways_Affected_by_M_itochondrial_Dysfunctions_Using_M_etabolomic_Approaches%3Fauto%3Ddownload"; window.loswp.translateUrl = "https://www.academia.edu/login?post_login_redirect_url=https%3A%2F%2Fwww.academia.edu%2F33009414%2Fmetabolites_Unraveling_Biochemical_Pathways_Affected_by_M_itochondrial_Dysfunctions_Using_M_etabolomic_Approaches%3Fshow_translation%3Dtrue"; window.loswp.previewableAttachments = [{"id":53122800,"identifier":"Attachment_53122800","shouldShowBulkDownload":false}]; window.loswp.shouldDetectTimezone = true; window.loswp.shouldShowBulkDownload = true; window.loswp.showSignupCaptcha = false window.loswp.willEdgeCache = false; window.loswp.work = {"work":{"id":33009414,"created_at":"2017-05-14T06:56:02.813-07:00","from_world_paper_id":null,"updated_at":"2025-02-01T18:57:03.704-08:00","_data":{"abstract":"Mitochondrial dysfunction(s) (MDs) can be defined as alterations in the mitochondria, including mitochondrial uncoupling, mitochondrial depolarization, inhibition of the mitochondrial respiratory chain, mitochondrial network fragmentation, mitochondrial or nuclear DNA mutations and the mitochondrial accumulation of protein aggregates. All these MDs are known to alter the capacity of ATP production and are observed in several pathological states/diseases, including cancer, obesity, muscle and neurological disorders. The induction of MDs can also alter the secretion of several metabolites, reactive oxygen species production and modify several cell-signalling pathways to resolve the mitochondrial dysfunction or ultimately trigger cell death. Many metabolites, such as fatty acids and derived compounds, could be secreted into the blood stream by cells suffering from mitochondrial alterations. In this review, we summarize how a mitochondrial uncoupling can modify metabolites, the signalling pathways and transcription factors involved in this process. We describe how to identify the causes or consequences of mitochondrial dysfunction using metabolomics (liquid and gas chromatography associated with mass spectrometry analysis, NMR spectroscopy) in the obesity and insulin resistance thematic. OPEN ACCESS","ai_title_tag":"Metabolomic Insights into Mitochondrial Dysfunction"},"document_type":"paper","pre_hit_view_count_baseline":null,"quality":"high","language":"en","title":"metabolites Unraveling Biochemical Pathways Affected by M itochondrial Dysfunctions Using M etabolomic Approaches","broadcastable":true,"draft":false,"has_indexable_attachment":true,"indexable":true}}["work"]; window.loswp.workCoauthors = [44153560,44230520]; window.loswp.locale = "en"; window.loswp.countryCode = "SG"; window.loswp.cwvAbTestBucket = ""; window.loswp.designVariant = "ds_vanilla"; window.loswp.fullPageMobileSutdModalVariant = "control"; window.loswp.useOptimizedScribd4genScript = false; window.loginModal = {}; window.loginModal.appleClientId = 'edu.academia.applesignon'; window.userInChina = "false";</script><script defer="" src="https://accounts.google.com/gsi/client"></script><div class="ds-loswp-container"><div class="ds-work-card--grid-container"><div class="ds-work-card--container js-loswp-work-card"><div class="ds-work-card--cover"><div class="ds-work-cover--wrapper"><div class="ds-work-cover--container"><button class="ds-work-cover--clickable js-swp-download-button" data-signup-modal="{"location":"swp-splash-paper-cover","attachmentId":53122800,"attachmentType":"pdf"}"><img alt="First page of “metabolites Unraveling Biochemical Pathways Affected by M itochondrial Dysfunctions Using M etabolomic Approaches”" class="ds-work-cover--cover-thumbnail" src="https://0.academia-photos.com/attachment_thumbnails/53122800/mini_magick20190122-21961-1arg9xb.png?1548148929" /><img alt="PDF Icon" class="ds-work-cover--file-icon" src="//a.academia-assets.com/images/single_work_splash/adobe_icon.svg" /><div class="ds-work-cover--hover-container"><span class="material-symbols-outlined" style="font-size: 20px" translate="no">download</span><p>Download Free PDF</p></div><div class="ds-work-cover--ribbon-container">Download Free PDF</div><div class="ds-work-cover--ribbon-triangle"></div></button></div></div></div><div class="ds-work-card--work-information"><h1 class="ds-work-card--work-title">metabolites Unraveling Biochemical Pathways Affected by M itochondrial Dysfunctions Using M etabolomic Approaches</h1><div class="ds-work-card--work-authors ds-work-card--detail"><a class="ds-work-card--author js-wsj-grid-card-author ds2-5-body-md ds2-5-body-link" data-author-id="44153560" href="https://independent.academia.edu/PatriciaRenard"><img alt="Profile image of Patricia Renard" class="ds-work-card--author-avatar" src="//a.academia-assets.com/images/s65_no_pic.png" />Patricia Renard</a><a class="ds-work-card--author js-wsj-grid-card-author ds2-5-body-md ds2-5-body-link" data-author-id="44230520" href="https://unamur.academia.edu/MRaes"><img alt="Profile image of Martine Raes" class="ds-work-card--author-avatar" src="//a.academia-assets.com/images/s65_no_pic.png" />Martine Raes</a></div><div class="ds-work-card--detail"><div class="ds-work-card--work-metadata"><div class="ds-work-card--work-metadata__stat"><span class="material-symbols-outlined" style="font-size: 20px" translate="no">visibility</span><p class="ds2-5-body-sm" id="work-metadata-view-count">…</p></div><div class="ds-work-card--work-metadata__stat"><span class="material-symbols-outlined" style="font-size: 20px" translate="no">description</span><p class="ds2-5-body-sm">48 pages</p></div><div class="ds-work-card--work-metadata__stat"><span class="material-symbols-outlined" style="font-size: 20px" translate="no">link</span><p class="ds2-5-body-sm">1 file</p></div></div><script>(async () => { const workId = 33009414; const worksViewsPath = "/v0/works/views?subdomain_param=api&work_ids%5B%5D=33009414"; const getWorkViews = async (workId) => { const response = await fetch(worksViewsPath); if (!response.ok) { throw new Error('Failed to load work views'); } const data = await response.json(); return data.views[workId]; }; // Get the view count for the work - we send this immediately rather than waiting for // the DOM to load, so it can be available as soon as possible (but without holding up // the backend or other resource requests, because it's a bit expensive and not critical). const viewCount = await getWorkViews(workId); const updateViewCount = (viewCount) => { try { const viewCountNumber = parseInt(viewCount, 10); if (viewCountNumber === 0) { // Remove the whole views element if there are zero views. document.getElementById('work-metadata-view-count')?.parentNode?.remove(); return; } const commaizedViewCount = viewCountNumber.toLocaleString(); const viewCountBody = document.getElementById('work-metadata-view-count'); if (!viewCountBody) { throw new Error('Failed to find work views element'); } viewCountBody.textContent = `${commaizedViewCount} views`; } catch (error) { // Remove the whole views element if there was some issue parsing. document.getElementById('work-metadata-view-count')?.parentNode?.remove(); throw new Error(`Failed to parse view count: ${viewCount}`, error); } }; // If the DOM is still loading, wait for it to be ready before updating the view count. if (document.readyState === "loading") { document.addEventListener('DOMContentLoaded', () => { updateViewCount(viewCount); }); // Otherwise, just update it immediately. } else { updateViewCount(viewCount); } })();</script></div><p class="ds-work-card--work-abstract ds-work-card--detail ds2-5-body-md">Mitochondrial dysfunction(s) (MDs) can be defined as alterations in the mitochondria, including mitochondrial uncoupling, mitochondrial depolarization, inhibition of the mitochondrial respiratory chain, mitochondrial network fragmentation, mitochondrial or nuclear DNA mutations and the mitochondrial accumulation of protein aggregates. All these MDs are known to alter the capacity of ATP production and are observed in several pathological states/diseases, including cancer, obesity, muscle and neurological disorders. The induction of MDs can also alter the secretion of several metabolites, reactive oxygen species production and modify several cell-signalling pathways to resolve the mitochondrial dysfunction or ultimately trigger cell death. Many metabolites, such as fatty acids and derived compounds, could be secreted into the blood stream by cells suffering from mitochondrial alterations. In this review, we summarize how a mitochondrial uncoupling can modify metabolites, the signalling pathways and transcription factors involved in this process. We describe how to identify the causes or consequences of mitochondrial dysfunction using metabolomics (liquid and gas chromatography associated with mass spectrometry analysis, NMR spectroscopy) in the obesity and insulin resistance thematic. OPEN ACCESS</p><div class="ds-work-card--button-container"><button class="ds2-5-button js-swp-download-button" data-signup-modal="{"location":"continue-reading-button--work-card","attachmentId":53122800,"attachmentType":"pdf","workUrl":"https://www.academia.edu/33009414/metabolites_Unraveling_Biochemical_Pathways_Affected_by_M_itochondrial_Dysfunctions_Using_M_etabolomic_Approaches"}">See full PDF</button><button class="ds2-5-button ds2-5-button--secondary js-swp-download-button" data-signup-modal="{"location":"download-pdf-button--work-card","attachmentId":53122800,"attachmentType":"pdf","workUrl":"https://www.academia.edu/33009414/metabolites_Unraveling_Biochemical_Pathways_Affected_by_M_itochondrial_Dysfunctions_Using_M_etabolomic_Approaches"}"><span class="material-symbols-outlined" style="font-size: 20px" translate="no">download</span>Download PDF</button></div><div class="ds-signup-banner-trigger-container"><div class="ds-signup-banner-trigger ds-signup-banner-trigger-control"></div></div><div class="ds-signup-banner ds-signup-banner-control"><div id="ds-signup-banner-close-button"><button class="ds2-5-button ds2-5-button--secondary ds2-5-button--inverse"><span class="material-symbols-outlined" style="font-size: 20px" translate="no">close</span></button></div><div class="ds-signup-banner-ctas"><img src="//a.academia-assets.com/images/academia-logo-capital-white.svg" /><h4 class="ds2-5-heading-serif-sm">Sign up for access to the world's latest research</h4><button class="ds2-5-button ds2-5-button--inverse ds2-5-button--full-width js-swp-download-button" data-signup-modal="{"location":"signup-banner"}">Sign up for free<span class="material-symbols-outlined" style="font-size: 20px" translate="no">arrow_forward</span></button></div><div class="ds-signup-banner-divider"></div><div class="ds-signup-banner-reasons"><div class="ds-signup-banner-reasons-item"><span class="material-symbols-outlined" style="font-size: 24px" translate="no">check</span><span>Get notified about relevant papers</span></div><div class="ds-signup-banner-reasons-item"><span class="material-symbols-outlined" style="font-size: 24px" translate="no">check</span><span>Save papers to use in your research</span></div><div class="ds-signup-banner-reasons-item"><span class="material-symbols-outlined" style="font-size: 24px" translate="no">check</span><span>Join the discussion with peers</span></div><div class="ds-signup-banner-reasons-item"><span class="material-symbols-outlined" style="font-size: 24px" translate="no">check</span><span>Track your impact</span></div></div></div><script>(() => { // Set up signup banner show/hide behavior: // 1. If the signup banner trigger (a 242px-high* invisible div underneath the 'See Full PDF' / 'Download PDF' buttons) // is already fully scrolled above the viewport, show the banner by default // 2. If the signup banner trigger is fully visible, show the banner // 3. If the signup banner trigger has even a few pixels scrolled below the viewport, hide the banner // // * 242px is the empirically determined height of the signup banner. It's better to be a bit taller than // necessary than too short, so it's fine that the mobile (small breakpoint) banner is shorter. // First check session storage for the signup banner's visibility state const signupBannerHidden = sessionStorage.getItem('ds-signup-banner-hidden'); if (signupBannerHidden === 'true') { return; } const signupBanner = document.querySelector('.ds-signup-banner'); const signupBannerTrigger = document.querySelector('.ds-signup-banner-trigger'); if (!signupBannerTrigger) { window.Sentry.captureMessage("Signup banner trigger not found"); return; } let footerShown = false; window.addEventListener('load', () => { const rect = signupBannerTrigger.getBoundingClientRect(); // If page loaded up already scrolled below the trigger (via scroll restoration), show the banner by default if (rect.bottom < 0) { footerShown = true; signupBanner.classList.add('ds-signup-banner-visible'); } }); // Wait for trigger to fully enter viewport before showing banner (ensures PDF CTAs are never covered by banner) const observer = new IntersectionObserver((entries) => { entries.forEach(entry => { if (entry.isIntersecting && !footerShown) { footerShown = true; signupBanner.classList.add('ds-signup-banner-visible'); } else if (!entry.isIntersecting && footerShown) { if (signupBannerTrigger.getBoundingClientRect().bottom > 0) { footerShown = false; signupBanner.classList.remove('ds-signup-banner-visible'); } } }); }); observer.observe(signupBannerTrigger); // Set up signup banner close button event handler: const signupBannerCloseButton = document.querySelector('#ds-signup-banner-close-button'); signupBannerCloseButton.addEventListener('click', () => { signupBanner.classList.remove('ds-signup-banner-visible'); observer.unobserve(signupBannerTrigger); // Store the signup banner's visibility state in session storage sessionStorage.setItem('ds-signup-banner-hidden', 'true'); }); })();</script></div></div></div><div data-auto_select="false" data-client_id="331998490334-rsn3chp12mbkiqhl6e7lu2q0mlbu0f1b" data-doc_id="53122800" data-landing_url="https://www.academia.edu/33009414/metabolites_Unraveling_Biochemical_Pathways_Affected_by_M_itochondrial_Dysfunctions_Using_M_etabolomic_Approaches" data-login_uri="https://www.academia.edu/registrations/google_one_tap" data-moment_callback="onGoogleOneTapEvent" id="g_id_onload"></div><div class="ds-top-related-works--grid-container"><div class="ds-related-content--container ds-top-related-works--container"><h2 class="ds-related-content--heading">Related papers</h2><div class="ds-related-work--container js-wsj-grid-card" data-collection-position="0" data-entity-id="72756658" data-sort-order="default"><a class="ds-related-work--title js-wsj-grid-card-title ds2-5-body-md ds2-5-body-link" href="https://www.academia.edu/72756658/Review_Unraveling_Biochemical_Pathways_Affected_by_Mitochondrial_Dysfunctions_Using_Metabolomic_Approaches">Review Unraveling Biochemical Pathways Affected by Mitochondrial Dysfunctions Using Metabolomic Approaches</a><div class="ds-related-work--metadata"><a class="js-wsj-grid-card-author ds2-5-body-sm ds2-5-body-link" data-author-id="44230520" href="https://unamur.academia.edu/MRaes">Martine Raes</a></div><p class="ds-related-work--metadata ds2-5-body-xs">2014</p><p class="ds-related-work--abstract ds2-5-body-sm">Mitochondrial dysfunction(s) (MDs) can be defined as alterations in the mitochondria, including mitochondrial uncoupling, mitochondrial depolarization, inhibition of the mitochondrial respiratory chain, mitochondrial network fragmentation, mitochondrial or nuclear DNA mutations and the mitochondrial accumulation of protein aggregates. All these MDs are known to alter the capacity of ATP production and are observed in several pathological states/diseases, including cancer, obesity, muscle and neurological disorders. The induction of MDs can also alter the secretion of several metabolites, reactive oxygen species production and modify several cell-signalling pathways to resolve the mitochondrial dysfunction or ultimately trigger cell death. Many metabolites, such as fatty acids and derived compounds, could be secreted into the blood stream by cells suffering from mitochondrial alterations. In this review, we summarize how a mitochondrial uncoupling can modify metabolites, the signalling pathways and transcription factors involved in this process. We describe how to identify the causes or consequences of mitochondrial dysfunction using metabolomics (liquid and gas chromatography associated with mass spectrometry analysis, NMR spectroscopy) in the obesity and insulin resistance thematic.</p><div class="ds-related-work--ctas"><button class="ds2-5-text-link ds2-5-text-link--inline js-swp-download-button" data-signup-modal="{"location":"wsj-grid-card-download-pdf-modal","work_title":"Review Unraveling Biochemical Pathways Affected by Mitochondrial Dysfunctions Using Metabolomic Approaches","attachmentId":81558155,"attachmentType":"pdf","work_url":"https://www.academia.edu/72756658/Review_Unraveling_Biochemical_Pathways_Affected_by_Mitochondrial_Dysfunctions_Using_Metabolomic_Approaches","alternativeTracking":true}"><span class="material-symbols-outlined" style="font-size: 18px" translate="no">download</span><span class="ds2-5-text-link__content">Download free PDF</span></button><a class="ds2-5-text-link ds2-5-text-link--inline js-wsj-grid-card-view-pdf" href="https://www.academia.edu/72756658/Review_Unraveling_Biochemical_Pathways_Affected_by_Mitochondrial_Dysfunctions_Using_Metabolomic_Approaches"><span class="ds2-5-text-link__content">View PDF</span><span class="material-symbols-outlined" style="font-size: 18px" translate="no">chevron_right</span></a></div></div><div class="ds-related-work--container js-wsj-grid-card" data-collection-position="1" data-entity-id="14815133" data-sort-order="default"><a class="ds-related-work--title js-wsj-grid-card-title ds2-5-body-md ds2-5-body-link" href="https://www.academia.edu/14815133/Unraveling_Biochemical_Pathways_Affected_by_Mitochondrial_Dysfunctions_Using_Metabolomic_Approaches">Unraveling Biochemical Pathways Affected by Mitochondrial Dysfunctions Using Metabolomic Approaches</a><div class="ds-related-work--metadata"><a class="js-wsj-grid-card-author ds2-5-body-sm ds2-5-body-link" data-author-id="33773769" href="https://unamur.academia.edu/St%C3%A9phaneDemine">Stéphane Demine</a><span>, </span><a class="js-wsj-grid-card-author ds2-5-body-sm ds2-5-body-link" data-author-id="33624084" href="https://unamur.academia.edu/ThierryArnould">Thierry Arnould</a></div><p class="ds-related-work--metadata ds2-5-body-xs">Metabolites, 2014</p><p class="ds-related-work--abstract ds2-5-body-sm">Mitochondrial dysfunction(s) (MDs) can be defined as alterations in the mitochondria, including mitochondrial uncoupling, mitochondrial depolarization, inhibition of the mitochondrial respiratory chain, mitochondrial network fragmentation, mitochondrial or nuclear DNA mutations and the mitochondrial accumulation of protein aggregates. All these MDs are known to alter the capacity of ATP production and are observed in several pathological states/diseases, including cancer, obesity, muscle and neurological disorders. The induction of MDs can also alter the secretion of several metabolites, reactive oxygen species production and modify several cell-signalling pathways to resolve the mitochondrial dysfunction or ultimately trigger cell death. Many metabolites, such as fatty acids and derived compounds, could be secreted into the blood stream by cells suffering from mitochondrial alterations. In this review, we summarize how a mitochondrial uncoupling can modify metabolites, the signalling pathways and transcription factors involved in this process. We describe how to identify the causes or consequences of mitochondrial dysfunction using metabolomics (liquid and gas chromatography associated with mass spectrometry analysis, NMR spectroscopy) in the obesity and insulin resistance thematic.</p><div class="ds-related-work--ctas"><button class="ds2-5-text-link ds2-5-text-link--inline js-swp-download-button" data-signup-modal="{"location":"wsj-grid-card-download-pdf-modal","work_title":"Unraveling Biochemical Pathways Affected by Mitochondrial Dysfunctions Using Metabolomic Approaches","attachmentId":43878292,"attachmentType":"pdf","work_url":"https://www.academia.edu/14815133/Unraveling_Biochemical_Pathways_Affected_by_Mitochondrial_Dysfunctions_Using_Metabolomic_Approaches","alternativeTracking":true}"><span class="material-symbols-outlined" style="font-size: 18px" translate="no">download</span><span class="ds2-5-text-link__content">Download free PDF</span></button><a class="ds2-5-text-link ds2-5-text-link--inline js-wsj-grid-card-view-pdf" href="https://www.academia.edu/14815133/Unraveling_Biochemical_Pathways_Affected_by_Mitochondrial_Dysfunctions_Using_Metabolomic_Approaches"><span class="ds2-5-text-link__content">View PDF</span><span class="material-symbols-outlined" style="font-size: 18px" translate="no">chevron_right</span></a></div></div><div class="ds-related-work--container js-wsj-grid-card" data-collection-position="2" data-entity-id="18993980" data-sort-order="default"><a class="ds-related-work--title js-wsj-grid-card-title ds2-5-body-md ds2-5-body-link" href="https://www.academia.edu/18993980/Metabolomic_Profiling_Reveals_Mitochondrial_Derived_Lipid_Biomarkers_That_Drive_Obesity_Associated_Inflammation">Metabolomic Profiling Reveals Mitochondrial-Derived Lipid Biomarkers That Drive Obesity-Associated Inflammation</a><div class="ds-related-work--metadata"><a class="js-wsj-grid-card-author ds2-5-body-sm ds2-5-body-link" data-author-id="39142563" href="https://independent.academia.edu/PeifenKuan">Pei-fen Kuan</a><span>, </span><a class="js-wsj-grid-card-author ds2-5-body-sm ds2-5-body-link" data-author-id="39234096" href="https://independent.academia.edu/OConnellThomas">Thomas O'Connell</a></div><p class="ds-related-work--metadata ds2-5-body-xs">PLoS ONE, 2012</p><p class="ds-related-work--abstract ds2-5-body-sm">Obesity has reached epidemic proportions worldwide. Several animal models of obesity exist, but studies are lacking that compare traditional lard-based high fat diets (HFD) to ''Cafeteria diets'' (CAF) consisting of nutrient poor human junk food. Our previous work demonstrated the rapid and severe obesogenic and inflammatory consequences of CAF compared to HFD including rapid weight gain, markers of Metabolic Syndrome, multi-tissue lipid accumulation, and dramatic inflammation. To identify potential mediators of CAF-induced obesity and Metabolic Syndrome, we used metabolomic analysis to profile serum, muscle, and white adipose from rats fed CAF, HFD, or standard control diets. Principle component analysis identified elevations in clusters of fatty acids and acylcarnitines. These increases in metabolites were associated with systemic mitochondrial dysfunction that paralleled weight gain, physiologic measures of Metabolic Syndrome, and tissue inflammation in CAF-fed rats. Spearman pairwise correlations between metabolites, physiologic, and histologic findings revealed strong correlations between elevated markers of inflammation in CAF-fed animals, measured as crown like structures in adipose, and specifically the pro-inflammatory saturated fatty acids and oxidation intermediates laurate and lauroyl carnitine. Treatment of bone marrow-derived macrophages with lauroyl carnitine polarized macrophages towards the M1 pro-inflammatory phenotype through downregulation of AMPK and secretion of pro-inflammatory cytokines. Results presented herein demonstrate that compared to a traditional HFD model, the CAF diet provides a robust model for diet-induced human obesity, which models Metabolic Syndrome-related mitochondrial dysfunction in serum, muscle, and adipose, along with pro-inflammatory metabolite alterations. These data also suggest that modifying the availability or metabolism of saturated fatty acids may limit the inflammation associated with obesity leading to Metabolic Syndrome.</p><div class="ds-related-work--ctas"><button class="ds2-5-text-link ds2-5-text-link--inline js-swp-download-button" data-signup-modal="{"location":"wsj-grid-card-download-pdf-modal","work_title":"Metabolomic Profiling Reveals Mitochondrial-Derived Lipid Biomarkers That Drive Obesity-Associated Inflammation","attachmentId":40371795,"attachmentType":"pdf","work_url":"https://www.academia.edu/18993980/Metabolomic_Profiling_Reveals_Mitochondrial_Derived_Lipid_Biomarkers_That_Drive_Obesity_Associated_Inflammation","alternativeTracking":true}"><span class="material-symbols-outlined" style="font-size: 18px" translate="no">download</span><span class="ds2-5-text-link__content">Download free PDF</span></button><a class="ds2-5-text-link ds2-5-text-link--inline js-wsj-grid-card-view-pdf" href="https://www.academia.edu/18993980/Metabolomic_Profiling_Reveals_Mitochondrial_Derived_Lipid_Biomarkers_That_Drive_Obesity_Associated_Inflammation"><span class="ds2-5-text-link__content">View PDF</span><span class="material-symbols-outlined" style="font-size: 18px" translate="no">chevron_right</span></a></div></div><div class="ds-related-work--container js-wsj-grid-card" data-collection-position="3" data-entity-id="31720228" data-sort-order="default"><a class="ds-related-work--title js-wsj-grid-card-title ds2-5-body-md ds2-5-body-link" href="https://www.academia.edu/31720228/Linking_energy_metabolism_to_dysfunctions_in_mitochondrial_respiration_A_metabolomics_in_vitro_approach">Linking energy metabolism to dysfunctions in mitochondrial respiration – A metabolomics in vitro approach</a><div class="ds-related-work--metadata"><a class="js-wsj-grid-card-author ds2-5-body-sm ds2-5-body-link" data-author-id="61026483" href="https://basf.academia.edu/RobertLandsiedel">Robert Landsiedel</a></div><p class="ds-related-work--metadata ds2-5-body-xs">Toxicology Letters, 2011</p><p class="ds-related-work--abstract ds2-5-body-sm">The study presented here describes the application of metabolite profiling of highly polar, intracellular metabolites after incubation of a mammalian fibroblast cell line with inhibitors of mitochondrial function. A metabolomics approach was used to assess the complex response of the cellular energy metabolism. Metabolic profiles of phosphorylated and carboxylated intracellular metabolites were assessed by UPLC-MS/MS and used to predict the mode of mitochondrial toxicity. Based on distinct metabolic patterns, multivariate data analysis allowed for the discrimination of two groups of toxins: inhibitors of the electron transport in mitochondrial membranes (complex IV inhibitors) and uncouplers of oxidative phosphorylation. Beyond these known interferences, metabolic profiling was able to reveal additional inhibitory effects on the cellular energy metabolism. Most prominently, for three of the toxins, metabolic patterns also disclosed an enhanced activity of the glycerol phosphate shuttle inferring the inhibition of NADH dehydrogenase at complex I. Secondly, inhibition of the electron transport was accompanied by a limiting availability of citric acid cycle intermediates and aspartate. Concomitantly, specific perturbations of the purine nucleotide cycle were observed. We have shown here that metabolomic approaches may assist to predict complex modes of action of toxic compounds on cellular level as well as to unravel specific dysfunctions in the energy metabolism.</p><div class="ds-related-work--ctas"><button class="ds2-5-text-link ds2-5-text-link--inline js-swp-download-button" data-signup-modal="{"location":"wsj-grid-card-download-pdf-modal","work_title":"Linking energy metabolism to dysfunctions in mitochondrial respiration – A metabolomics in vitro approach","attachmentId":52032891,"attachmentType":"pdf","work_url":"https://www.academia.edu/31720228/Linking_energy_metabolism_to_dysfunctions_in_mitochondrial_respiration_A_metabolomics_in_vitro_approach","alternativeTracking":true}"><span class="material-symbols-outlined" style="font-size: 18px" translate="no">download</span><span class="ds2-5-text-link__content">Download free PDF</span></button><a class="ds2-5-text-link ds2-5-text-link--inline js-wsj-grid-card-view-pdf" href="https://www.academia.edu/31720228/Linking_energy_metabolism_to_dysfunctions_in_mitochondrial_respiration_A_metabolomics_in_vitro_approach"><span class="ds2-5-text-link__content">View PDF</span><span class="material-symbols-outlined" style="font-size: 18px" translate="no">chevron_right</span></a></div></div><div class="ds-related-work--container js-wsj-grid-card" data-collection-position="4" data-entity-id="3574906" data-sort-order="default"><a class="ds-related-work--title js-wsj-grid-card-title ds2-5-body-md ds2-5-body-link" href="https://www.academia.edu/3574906/Mitochondrial_Fatty_Acid_Oxidation_in_Obesity">Mitochondrial Fatty Acid Oxidation in Obesity</a><div class="ds-related-work--metadata"><a class="js-wsj-grid-card-author ds2-5-body-sm ds2-5-body-link" data-author-id="247779" href="https://ub.academia.edu/JoanMirBonn%C3%ADn">Joan Mir Bonnín</a></div><p class="ds-related-work--metadata ds2-5-body-xs">Antioxidants & redox signaling, 2012</p><p class="ds-related-work--abstract ds2-5-body-sm">Significance: Current lifestyles with high-energy diets and little exercise are triggering an alarming growth in obesity. Excess of adiposity is leading to severe increases in associated pathologies, such as insulin resistance, type 2 diabetes, atherosclerosis, cancer, arthritis, asthma, and hypertension. This, together with the lack of efficient obesity drugs, is the driving force behind much research. Recent Advances: Traditional anti-obesity strategies focused on reducing food intake and increasing physical activity. However, recent results suggest that enhancing cellular energy expenditure may be an attractive alternative therapy. Critical Issues: This review evaluates recent discoveries regarding mitochondrial fatty acid oxidation (FAO) and its potential as a therapy for obesity. We focus on the still controversial beneficial effects of increased FAO in liver and muscle, recent studies on how to potentiate adipose tissue energy expenditure, and the different hypotheses involving FAO and the reactive oxygen species production in the hypothalamic control of food intake. Future Directions: The present review aims to provide an overview of novel anti-obesity strategies that target mitochondrial FAO and that will definitively be of high interest in the future research to fight against obesity-related disorders. Antioxid. Redox</p><div class="ds-related-work--ctas"><button class="ds2-5-text-link ds2-5-text-link--inline js-swp-download-button" data-signup-modal="{"location":"wsj-grid-card-download-pdf-modal","work_title":"Mitochondrial Fatty Acid Oxidation in Obesity","attachmentId":31281881,"attachmentType":"pdf","work_url":"https://www.academia.edu/3574906/Mitochondrial_Fatty_Acid_Oxidation_in_Obesity","alternativeTracking":true}"><span class="material-symbols-outlined" style="font-size: 18px" translate="no">download</span><span class="ds2-5-text-link__content">Download free PDF</span></button><a class="ds2-5-text-link ds2-5-text-link--inline js-wsj-grid-card-view-pdf" href="https://www.academia.edu/3574906/Mitochondrial_Fatty_Acid_Oxidation_in_Obesity"><span class="ds2-5-text-link__content">View PDF</span><span class="material-symbols-outlined" style="font-size: 18px" translate="no">chevron_right</span></a></div></div><div class="ds-related-work--container js-wsj-grid-card" data-collection-position="5" data-entity-id="97505906" data-sort-order="default"><a class="ds-related-work--title js-wsj-grid-card-title ds2-5-body-md ds2-5-body-link" href="https://www.academia.edu/97505906/Traditional_and_novel_tools_to_probe_the_mitochondrial_metabolism_in_health_and_disease">Traditional and novel tools to probe the mitochondrial metabolism in health and disease</a><div class="ds-related-work--metadata"><a class="js-wsj-grid-card-author ds2-5-body-sm ds2-5-body-link" data-author-id="259032690" href="https://independent.academia.edu/YanfeiZHANG16">Yanfei ZHANG</a></div><p class="ds-related-work--metadata ds2-5-body-xs">Wiley interdisciplinary reviews. Systems biology and medicine, 2017</p><p class="ds-related-work--abstract ds2-5-body-sm">Mitochondrial metabolism links energy production to other essential cellular processes such as signaling, cellular differentiation, and apoptosis. In addition to producing adenosine triphosphate (ATP) as an energy source, mitochondria are responsible for the synthesis of a myriad of important metabolites and cofactors such as tetrahydrofolate, α-ketoacids, steroids, aminolevulinic acid, biotin, lipoic acid, acetyl-CoA, iron-sulfur clusters, heme, and ubiquinone. Furthermore, mitochondria and their metabolism have been implicated in aging and several human diseases, including inherited mitochondrial disorders, cardiac dysfunction, heart failure, neurodegenerative diseases, diabetes, and cancer. Therefore, there is great interest in understanding mitochondrial metabolism and the complex relationship it has with other cellular processes. A large number of studies on mitochondrial metabolism have been conducted in the last 50 years, taking a broad range of approaches. In this review, we...</p><div class="ds-related-work--ctas"><button class="ds2-5-text-link ds2-5-text-link--inline js-swp-download-button" data-signup-modal="{"location":"wsj-grid-card-download-pdf-modal","work_title":"Traditional and novel tools to probe the mitochondrial metabolism in health and disease","attachmentId":99108796,"attachmentType":"pdf","work_url":"https://www.academia.edu/97505906/Traditional_and_novel_tools_to_probe_the_mitochondrial_metabolism_in_health_and_disease","alternativeTracking":true}"><span class="material-symbols-outlined" style="font-size: 18px" translate="no">download</span><span class="ds2-5-text-link__content">Download free PDF</span></button><a class="ds2-5-text-link ds2-5-text-link--inline js-wsj-grid-card-view-pdf" href="https://www.academia.edu/97505906/Traditional_and_novel_tools_to_probe_the_mitochondrial_metabolism_in_health_and_disease"><span class="ds2-5-text-link__content">View PDF</span><span class="material-symbols-outlined" style="font-size: 18px" translate="no">chevron_right</span></a></div></div><div class="ds-related-work--container js-wsj-grid-card" data-collection-position="6" data-entity-id="24567105" data-sort-order="default"><a class="ds-related-work--title js-wsj-grid-card-title ds2-5-body-md ds2-5-body-link" href="https://www.academia.edu/24567105/Mitochondrial_dysfunction_and_lipotoxicity">Mitochondrial dysfunction and lipotoxicity</a><div class="ds-related-work--metadata"><a class="js-wsj-grid-card-author ds2-5-body-sm ds2-5-body-link" data-author-id="47356324" href="https://independent.academia.edu/MatthijsHesselink">Matthijs Hesselink</a></div><p class="ds-related-work--metadata ds2-5-body-xs">Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids, 2010</p><div class="ds-related-work--ctas"><button class="ds2-5-text-link ds2-5-text-link--inline js-swp-download-button" data-signup-modal="{"location":"wsj-grid-card-download-pdf-modal","work_title":"Mitochondrial dysfunction and lipotoxicity","attachmentId":44896316,"attachmentType":"pdf","work_url":"https://www.academia.edu/24567105/Mitochondrial_dysfunction_and_lipotoxicity","alternativeTracking":true}"><span class="material-symbols-outlined" style="font-size: 18px" translate="no">download</span><span class="ds2-5-text-link__content">Download free PDF</span></button><a class="ds2-5-text-link ds2-5-text-link--inline js-wsj-grid-card-view-pdf" href="https://www.academia.edu/24567105/Mitochondrial_dysfunction_and_lipotoxicity"><span class="ds2-5-text-link__content">View PDF</span><span class="material-symbols-outlined" style="font-size: 18px" translate="no">chevron_right</span></a></div></div><div class="ds-related-work--container js-wsj-grid-card" data-collection-position="7" data-entity-id="80038197" data-sort-order="default"><a class="ds-related-work--title js-wsj-grid-card-title ds2-5-body-md ds2-5-body-link" href="https://www.academia.edu/80038197/Mitochondrial_dysfunction_and_metabolic_syndrome_looking_for_environmental_factors">Mitochondrial dysfunction and metabolic syndrome—looking for environmental factors</a><div class="ds-related-work--metadata"><a class="js-wsj-grid-card-author ds2-5-body-sm ds2-5-body-link" data-author-id="208632760" href="https://independent.academia.edu/EunBoShim">Eun Bo Shim</a></div><p class="ds-related-work--metadata ds2-5-body-xs">Biochimica et Biophysica Acta (BBA) - General Subjects, 2010</p><p class="ds-related-work--abstract ds2-5-body-sm">The centerpiece of the pathophysiologic mechanism of metabolic syndrome is insulin resistance. Recently, it is becoming evident that mitochondrial dysfunction is closely related to insulin resistance and metabolic syndrome. The underlying mechanism of mitochondrial dysfunction is very complex, which includes genetic factors from both nuclear and mitochondrial genome and numerous environmental factors. Several mitochondrial DNA polymorphisms are associated with the components of metabolic syndrome. Numerous chemicals and drugs may cause mitochondrial dysfunction and insulin resistance. Notably, it was recently reported that serum levels of several mitochondrial toxins, such as persistent organic pollutants are associated with metabolic syndrome, which necessitates further investigation to reveal its precise mechanism. Given that the health impact of metabolic syndrome is tremendous, it is necessary to develop therapeutic modalities to correct mitochondrial dysfunction or at least to halt its aggravation. In this regard, exercise can improve both mitochondrial function and insulin sensitivity, and some pharmaceutical agents were reported to improve mitochondrial function. However, further studies are warranted to find more effective therapeutic strategies to treat mitochondrial dysfunction. By doing so, we can also shed light on the path of research for other diseases related to mitochondrial dysfunction.</p><div class="ds-related-work--ctas"><button class="ds2-5-text-link ds2-5-text-link--inline js-swp-download-button" data-signup-modal="{"location":"wsj-grid-card-download-pdf-modal","work_title":"Mitochondrial dysfunction and metabolic syndrome—looking for environmental factors","attachmentId":86552962,"attachmentType":"pdf","work_url":"https://www.academia.edu/80038197/Mitochondrial_dysfunction_and_metabolic_syndrome_looking_for_environmental_factors","alternativeTracking":true}"><span class="material-symbols-outlined" style="font-size: 18px" translate="no">download</span><span class="ds2-5-text-link__content">Download free PDF</span></button><a class="ds2-5-text-link ds2-5-text-link--inline js-wsj-grid-card-view-pdf" href="https://www.academia.edu/80038197/Mitochondrial_dysfunction_and_metabolic_syndrome_looking_for_environmental_factors"><span class="ds2-5-text-link__content">View PDF</span><span class="material-symbols-outlined" style="font-size: 18px" translate="no">chevron_right</span></a></div></div><div class="ds-related-work--container js-wsj-grid-card" data-collection-position="8" data-entity-id="123724588" data-sort-order="default"><a class="ds-related-work--title js-wsj-grid-card-title ds2-5-body-md ds2-5-body-link" href="https://www.academia.edu/123724588/Dysregulated_Mitochondrial_Dynamics_and_Metabolism_in_Obesity_Diabetes_and_Cancer">Dysregulated Mitochondrial Dynamics and Metabolism in Obesity, Diabetes, and Cancer</a><div class="ds-related-work--metadata"><a class="js-wsj-grid-card-author ds2-5-body-sm ds2-5-body-link" data-author-id="36333099" href="https://independent.academia.edu/LeiJiang13">Lei Jiang</a></div><p class="ds-related-work--metadata ds2-5-body-xs">Frontiers in Endocrinology, 2019</p><p class="ds-related-work--abstract ds2-5-body-sm">Metabolism describes the life-sustaining chemical reactions in organisms that provide both energy and building blocks for cellular survival and proliferation. Dysregulated metabolism leads to many life-threatening diseases including obesity, diabetes, and cancer. Mitochondria, subcellular organelles, contain the central energy-producing metabolic pathway, the tricarboxylic acid (TCA) cycle. Also, mitochondria exist in a dynamic network orchestrated by extracellular nutrient levels and intracellular energy needs. Upon stimulation, mitochondria undergo consistent interchange through fusion (small to big) and fission (big to small) processes. Mitochondrial fusion is primarily controlled by three GTPases, mitofusin 1 (Mfn1), Mfn2, and optic atrophy 1 (Opa1), while mitochondrial fission is primarily regulated by GTPase dynamin-related protein 1 (Drp1). Dysregulated activity of these GTPases results in disrupted mitochondrial dynamics and cellular metabolism. This review will update the metabolic roles of these GTPases in obesity, diabetes, and cancer.</p><div class="ds-related-work--ctas"><button class="ds2-5-text-link ds2-5-text-link--inline js-swp-download-button" data-signup-modal="{"location":"wsj-grid-card-download-pdf-modal","work_title":"Dysregulated Mitochondrial Dynamics and Metabolism in Obesity, Diabetes, and Cancer","attachmentId":118089570,"attachmentType":"pdf","work_url":"https://www.academia.edu/123724588/Dysregulated_Mitochondrial_Dynamics_and_Metabolism_in_Obesity_Diabetes_and_Cancer","alternativeTracking":true}"><span class="material-symbols-outlined" style="font-size: 18px" translate="no">download</span><span class="ds2-5-text-link__content">Download free PDF</span></button><a class="ds2-5-text-link ds2-5-text-link--inline js-wsj-grid-card-view-pdf" href="https://www.academia.edu/123724588/Dysregulated_Mitochondrial_Dynamics_and_Metabolism_in_Obesity_Diabetes_and_Cancer"><span class="ds2-5-text-link__content">View PDF</span><span class="material-symbols-outlined" style="font-size: 18px" translate="no">chevron_right</span></a></div></div><div class="ds-related-work--container js-wsj-grid-card" data-collection-position="9" data-entity-id="20775542" data-sort-order="default"><a class="ds-related-work--title js-wsj-grid-card-title ds2-5-body-md ds2-5-body-link" href="https://www.academia.edu/20775542/Molecular_Mechanisms_of_Insulin_Resistance_in_Humans_and_Their_Potential_Links_With_Mitochondrial_Dysfunction">Molecular Mechanisms of Insulin Resistance in Humans and Their Potential Links With Mitochondrial Dysfunction</a><div class="ds-related-work--metadata"><a class="js-wsj-grid-card-author ds2-5-body-sm ds2-5-body-link" data-author-id="42061759" href="https://independent.academia.edu/TheodoreCiaraldi">Theodore Ciaraldi</a></div><p class="ds-related-work--metadata ds2-5-body-xs">Diabetes, 2006</p><p class="ds-related-work--abstract ds2-5-body-sm">Recent studies using magnetic resonance spectroscopy have shown that decreased insulin-stimulated muscle glycogen synthesis due to a defect in insulin-stimulated glucose transport activity is a major factor in the pathogenesis of type 2 diabetes. The molecular mechanism underlying defective insulin-stimulated glucose transport activity can be attributed to increases in intramyocellular lipid metabolites such as fatty acyl CoAs and diacylglycerol, which in turn activate a serine/threonine kinase cascade, thus leading to defects in insulin signaling through Ser/Thr phosphorylation of insulin receptor substrate (IRS)-1. A similar mechanism is also observed in hepatic insulin resistance associated with nonalcoholic fatty liver, which is a common feature of type 2 diabetes, where increases in hepatocellular diacylglycerol content activate protein kinase C-, leading to reduced insulin-stimulated tyrosine phosphorylation of IRS-2. More recently, magnetic resonance spectroscopy studies in healthy lean elderly subjects and healthy lean insulin-resistant offspring of parents with type 2 diabetes have demonstrated that reduced mitochondrial function may predispose these individuals to intramyocellular lipid accumulation and insulin resistance. Further analysis has found that the reduction in mitochondrial function in the insulin-resistant offspring can be mostly attributed to reductions in mitochondrial density. By elucidating the cellular and molecular mechanisms responsible for insulin resistance, these studies provide potential new targets for the treatment and prevention of type 2 diabetes. Diabetes 55 (Suppl. 2):S9 -S15This article is based on a presentation at a symposium. The symposium and the publication of this article were made possible by an unrestricted educational grant from Servier.</p><div class="ds-related-work--ctas"><button class="ds2-5-text-link ds2-5-text-link--inline js-swp-download-button" data-signup-modal="{"location":"wsj-grid-card-download-pdf-modal","work_title":"Molecular Mechanisms of Insulin Resistance in Humans and Their Potential Links With Mitochondrial Dysfunction","attachmentId":41555481,"attachmentType":"pdf","work_url":"https://www.academia.edu/20775542/Molecular_Mechanisms_of_Insulin_Resistance_in_Humans_and_Their_Potential_Links_With_Mitochondrial_Dysfunction","alternativeTracking":true}"><span class="material-symbols-outlined" style="font-size: 18px" translate="no">download</span><span class="ds2-5-text-link__content">Download free PDF</span></button><a class="ds2-5-text-link ds2-5-text-link--inline js-wsj-grid-card-view-pdf" href="https://www.academia.edu/20775542/Molecular_Mechanisms_of_Insulin_Resistance_in_Humans_and_Their_Potential_Links_With_Mitochondrial_Dysfunction"><span class="ds2-5-text-link__content">View PDF</span><span class="material-symbols-outlined" style="font-size: 18px" translate="no">chevron_right</span></a></div></div></div></div><div class="ds-sticky-ctas--wrapper js-loswp-sticky-ctas hidden"><div class="ds-sticky-ctas--grid-container"><div class="ds-sticky-ctas--container"><button class="ds2-5-button js-swp-download-button" data-signup-modal="{"location":"continue-reading-button--sticky-ctas","attachmentId":53122800,"attachmentType":"pdf","workUrl":null}">See full PDF</button><button class="ds2-5-button ds2-5-button--secondary js-swp-download-button" data-signup-modal="{"location":"download-pdf-button--sticky-ctas","attachmentId":53122800,"attachmentType":"pdf","workUrl":null}"><span class="material-symbols-outlined" style="font-size: 20px" translate="no">download</span>Download PDF</button></div></div></div><div class="ds-below-fold--grid-container"><div class="ds-work--container js-loswp-embedded-document"><div class="attachment_preview" data-attachment="Attachment_53122800" style="display: none"><div class="js-scribd-document-container"><div class="scribd--document-loading js-scribd-document-loader" style="display: block;"><img alt="Loading..." src="//a.academia-assets.com/images/loaders/paper-load.gif" /><p>Loading Preview</p></div></div><div style="text-align: center;"><div class="scribd--no-preview-alert js-preview-unavailable"><p>Sorry, preview is currently unavailable. You can download the paper by clicking the button above.</p></div></div></div></div><div class="ds-sidebar--container js-work-sidebar"><div class="ds-related-content--container"><h2 class="ds-related-content--heading">Related papers</h2><div class="ds-related-work--container js-related-work-sidebar-card" data-collection-position="0" data-entity-id="50407134" data-sort-order="default"><a class="ds-related-work--title js-related-work-grid-card-title ds2-5-body-md ds2-5-body-link" href="https://www.academia.edu/50407134/Mitochondrial_Overload_and_Incomplete_Fatty_Acid_Oxidation_Contribute_to_Skeletal_Muscle_Insulin_Resistance">Mitochondrial Overload and Incomplete Fatty Acid Oxidation Contribute to Skeletal Muscle Insulin Resistance</a><div class="ds-related-work--metadata"><a class="js-related-work-grid-card-author ds2-5-body-sm ds2-5-body-link" data-author-id="51874383" href="https://independent.academia.edu/OlgaIlkayeva">Olga Ilkayeva</a></div><p class="ds-related-work--metadata ds2-5-body-xs">Cell Metabolism, 2008</p><div class="ds-related-work--ctas"><button class="ds2-5-text-link ds2-5-text-link--inline js-swp-download-button" data-signup-modal="{"location":"wsj-grid-card-download-pdf-modal","work_title":"Mitochondrial Overload and Incomplete Fatty Acid Oxidation Contribute to Skeletal Muscle Insulin Resistance","attachmentId":68407376,"attachmentType":"pdf","work_url":"https://www.academia.edu/50407134/Mitochondrial_Overload_and_Incomplete_Fatty_Acid_Oxidation_Contribute_to_Skeletal_Muscle_Insulin_Resistance","alternativeTracking":true}"><span class="material-symbols-outlined" style="font-size: 18px" translate="no">download</span><span class="ds2-5-text-link__content">Download free PDF</span></button><a class="ds2-5-text-link ds2-5-text-link--inline js-related-work-grid-card-view-pdf" href="https://www.academia.edu/50407134/Mitochondrial_Overload_and_Incomplete_Fatty_Acid_Oxidation_Contribute_to_Skeletal_Muscle_Insulin_Resistance"><span class="ds2-5-text-link__content">View PDF</span><span class="material-symbols-outlined" style="font-size: 18px" translate="no">chevron_right</span></a></div></div><div class="ds-related-work--container js-related-work-sidebar-card" data-collection-position="1" data-entity-id="17259881" data-sort-order="default"><a class="ds-related-work--title js-related-work-grid-card-title ds2-5-body-md ds2-5-body-link" href="https://www.academia.edu/17259881/Mitochondrial_oxidative_phosphorylation_obesity_and_diabetes">Mitochondrial oxidative phosphorylation, obesity and diabetes</a><div class="ds-related-work--metadata"><a class="js-related-work-grid-card-author ds2-5-body-sm ds2-5-body-link" data-author-id="36885677" href="https://independent.academia.edu/BidarWang">Bi-dar Wang</a></div><div class="ds-related-work--ctas"><button class="ds2-5-text-link ds2-5-text-link--inline js-swp-download-button" data-signup-modal="{"location":"wsj-grid-card-download-pdf-modal","work_title":"Mitochondrial oxidative phosphorylation, obesity and diabetes","attachmentId":42280105,"attachmentType":"pdf","work_url":"https://www.academia.edu/17259881/Mitochondrial_oxidative_phosphorylation_obesity_and_diabetes","alternativeTracking":true}"><span class="material-symbols-outlined" style="font-size: 18px" translate="no">download</span><span class="ds2-5-text-link__content">Download free PDF</span></button><a class="ds2-5-text-link ds2-5-text-link--inline js-related-work-grid-card-view-pdf" href="https://www.academia.edu/17259881/Mitochondrial_oxidative_phosphorylation_obesity_and_diabetes"><span class="ds2-5-text-link__content">View PDF</span><span class="material-symbols-outlined" style="font-size: 18px" translate="no">chevron_right</span></a></div></div><div class="ds-related-work--container js-related-work-sidebar-card" data-collection-position="2" data-entity-id="87890835" data-sort-order="default"><a class="ds-related-work--title js-related-work-grid-card-title ds2-5-body-md ds2-5-body-link" href="https://www.academia.edu/87890835/The_mitochondrial_derived_peptide_MOTS_c_is_a_regulator_of_plasma_metabolites_and_enhances_insulin_sensitivity">The mitochondrial‐derived peptide MOTS‐c is a regulator of plasma metabolites and enhances insulin sensitivity</a><div class="ds-related-work--metadata"><a class="js-related-work-grid-card-author ds2-5-body-sm ds2-5-body-link" data-author-id="229244837" href="https://independent.academia.edu/KelvinYen">Kelvin Yen</a></div><p class="ds-related-work--metadata ds2-5-body-xs">Physiological Reports, 2019</p><div class="ds-related-work--ctas"><button class="ds2-5-text-link ds2-5-text-link--inline js-swp-download-button" data-signup-modal="{"location":"wsj-grid-card-download-pdf-modal","work_title":"The mitochondrial‐derived peptide MOTS‐c is a regulator of plasma metabolites and enhances insulin sensitivity","attachmentId":91988606,"attachmentType":"pdf","work_url":"https://www.academia.edu/87890835/The_mitochondrial_derived_peptide_MOTS_c_is_a_regulator_of_plasma_metabolites_and_enhances_insulin_sensitivity","alternativeTracking":true}"><span class="material-symbols-outlined" style="font-size: 18px" translate="no">download</span><span class="ds2-5-text-link__content">Download free PDF</span></button><a class="ds2-5-text-link ds2-5-text-link--inline js-related-work-grid-card-view-pdf" href="https://www.academia.edu/87890835/The_mitochondrial_derived_peptide_MOTS_c_is_a_regulator_of_plasma_metabolites_and_enhances_insulin_sensitivity"><span class="ds2-5-text-link__content">View PDF</span><span class="material-symbols-outlined" style="font-size: 18px" translate="no">chevron_right</span></a></div></div><div class="ds-related-work--container js-related-work-sidebar-card" data-collection-position="3" data-entity-id="87351249" data-sort-order="default"><a class="ds-related-work--title js-related-work-grid-card-title ds2-5-body-md ds2-5-body-link" href="https://www.academia.edu/87351249/A_plasma_signature_of_human_mitochondrial_disease_revealed_through_metabolic_profiling_of_spent_media_from_cultured_muscle_cells">A plasma signature of human mitochondrial disease revealed through metabolic profiling of spent media from cultured muscle cells</a><div class="ds-related-work--metadata"><a class="js-related-work-grid-card-author ds2-5-body-sm ds2-5-body-link" data-author-id="40786692" href="https://independent.academia.edu/QiuweiXu">Qiuwei Xu</a></div><p class="ds-related-work--metadata ds2-5-body-xs">Proceedings of the National Academy of Sciences, 2010</p><div class="ds-related-work--ctas"><button class="ds2-5-text-link ds2-5-text-link--inline js-swp-download-button" data-signup-modal="{"location":"wsj-grid-card-download-pdf-modal","work_title":"A plasma signature of human mitochondrial disease revealed through metabolic profiling of spent media from cultured muscle cells","attachmentId":91584933,"attachmentType":"pdf","work_url":"https://www.academia.edu/87351249/A_plasma_signature_of_human_mitochondrial_disease_revealed_through_metabolic_profiling_of_spent_media_from_cultured_muscle_cells","alternativeTracking":true}"><span class="material-symbols-outlined" style="font-size: 18px" translate="no">download</span><span class="ds2-5-text-link__content">Download free PDF</span></button><a class="ds2-5-text-link ds2-5-text-link--inline js-related-work-grid-card-view-pdf" href="https://www.academia.edu/87351249/A_plasma_signature_of_human_mitochondrial_disease_revealed_through_metabolic_profiling_of_spent_media_from_cultured_muscle_cells"><span class="ds2-5-text-link__content">View PDF</span><span class="material-symbols-outlined" style="font-size: 18px" translate="no">chevron_right</span></a></div></div><div class="ds-related-work--container js-related-work-sidebar-card" data-collection-position="4" data-entity-id="90466457" data-sort-order="default"><a class="ds-related-work--title js-related-work-grid-card-title ds2-5-body-md ds2-5-body-link" href="https://www.academia.edu/90466457/The_Association_between_Obesity_and_Mitochondrial_Dysfunction_A_Mini_Review">The Association between Obesity and Mitochondrial Dysfunction: A Mini Review</a><div class="ds-related-work--metadata"><a class="js-related-work-grid-card-author ds2-5-body-sm ds2-5-body-link" data-author-id="25365880" href="https://independent.academia.edu/IoannisPatrikios">Ioannis Patrikios</a></div><p class="ds-related-work--metadata ds2-5-body-xs">2020</p><div class="ds-related-work--ctas"><button class="ds2-5-text-link ds2-5-text-link--inline js-swp-download-button" data-signup-modal="{"location":"wsj-grid-card-download-pdf-modal","work_title":"The Association between Obesity and Mitochondrial Dysfunction: A Mini Review","attachmentId":94022280,"attachmentType":"pdf","work_url":"https://www.academia.edu/90466457/The_Association_between_Obesity_and_Mitochondrial_Dysfunction_A_Mini_Review","alternativeTracking":true}"><span class="material-symbols-outlined" style="font-size: 18px" translate="no">download</span><span class="ds2-5-text-link__content">Download free PDF</span></button><a class="ds2-5-text-link ds2-5-text-link--inline js-related-work-grid-card-view-pdf" href="https://www.academia.edu/90466457/The_Association_between_Obesity_and_Mitochondrial_Dysfunction_A_Mini_Review"><span class="ds2-5-text-link__content">View PDF</span><span class="material-symbols-outlined" style="font-size: 18px" translate="no">chevron_right</span></a></div></div><div class="ds-related-work--container js-related-work-sidebar-card" data-collection-position="5" data-entity-id="49754681" data-sort-order="default"><a class="ds-related-work--title js-related-work-grid-card-title ds2-5-body-md ds2-5-body-link" href="https://www.academia.edu/49754681/Mitochondrial_Dysfunction_A_Basic_Mechanism_in_Inflammation_Related_Non_Communicable_Diseases_and_Therapeutic_Opportunities">Mitochondrial Dysfunction: A Basic Mechanism in Inflammation-Related Non-Communicable Diseases and Therapeutic Opportunities</a><div class="ds-related-work--metadata"><a class="js-related-work-grid-card-author ds2-5-body-sm ds2-5-body-link" data-author-id="11787836" href="https://independent.academia.edu/jorgejoven">jorge joven</a></div><p class="ds-related-work--metadata ds2-5-body-xs">Mediators of Inflammation, 2013</p><div class="ds-related-work--ctas"><button class="ds2-5-text-link ds2-5-text-link--inline js-swp-download-button" data-signup-modal="{"location":"wsj-grid-card-download-pdf-modal","work_title":"Mitochondrial Dysfunction: A Basic Mechanism in Inflammation-Related Non-Communicable Diseases and Therapeutic Opportunities","attachmentId":68002695,"attachmentType":"pdf","work_url":"https://www.academia.edu/49754681/Mitochondrial_Dysfunction_A_Basic_Mechanism_in_Inflammation_Related_Non_Communicable_Diseases_and_Therapeutic_Opportunities","alternativeTracking":true}"><span class="material-symbols-outlined" style="font-size: 18px" translate="no">download</span><span class="ds2-5-text-link__content">Download free PDF</span></button><a class="ds2-5-text-link ds2-5-text-link--inline js-related-work-grid-card-view-pdf" href="https://www.academia.edu/49754681/Mitochondrial_Dysfunction_A_Basic_Mechanism_in_Inflammation_Related_Non_Communicable_Diseases_and_Therapeutic_Opportunities"><span class="ds2-5-text-link__content">View PDF</span><span class="material-symbols-outlined" style="font-size: 18px" translate="no">chevron_right</span></a></div></div><div class="ds-related-work--container js-related-work-sidebar-card" data-collection-position="6" data-entity-id="17676854" data-sort-order="default"><a class="ds-related-work--title js-related-work-grid-card-title ds2-5-body-md ds2-5-body-link" href="https://www.academia.edu/17676854/Long_Chain_Fatty_Acid_Combustion_Rate_Is_Associated_with_Unique_Metabolite_Profiles_in_Skeletal_Muscle_Mitochondria">Long-Chain Fatty Acid Combustion Rate Is Associated with Unique Metabolite Profiles in Skeletal Muscle Mitochondria</a><div class="ds-related-work--metadata"><a class="js-related-work-grid-card-author ds2-5-body-sm ds2-5-body-link" data-author-id="37594162" href="https://independent.academia.edu/GertWohlgemuth">Gert Wohlgemuth</a><span>, </span><a class="js-related-work-grid-card-author ds2-5-body-sm ds2-5-body-link" data-author-id="31759945" href="https://uottawa.academia.edu/MaryEllenHarper">Mary-Ellen Harper</a></div><p class="ds-related-work--metadata ds2-5-body-xs">PLoS ONE, 2010</p><div class="ds-related-work--ctas"><button class="ds2-5-text-link ds2-5-text-link--inline js-swp-download-button" data-signup-modal="{"location":"wsj-grid-card-download-pdf-modal","work_title":"Long-Chain Fatty Acid Combustion Rate Is Associated with Unique Metabolite Profiles in Skeletal Muscle Mitochondria","attachmentId":39652721,"attachmentType":"pdf","work_url":"https://www.academia.edu/17676854/Long_Chain_Fatty_Acid_Combustion_Rate_Is_Associated_with_Unique_Metabolite_Profiles_in_Skeletal_Muscle_Mitochondria","alternativeTracking":true}"><span class="material-symbols-outlined" style="font-size: 18px" translate="no">download</span><span class="ds2-5-text-link__content">Download free PDF</span></button><a class="ds2-5-text-link ds2-5-text-link--inline js-related-work-grid-card-view-pdf" href="https://www.academia.edu/17676854/Long_Chain_Fatty_Acid_Combustion_Rate_Is_Associated_with_Unique_Metabolite_Profiles_in_Skeletal_Muscle_Mitochondria"><span class="ds2-5-text-link__content">View PDF</span><span class="material-symbols-outlined" style="font-size: 18px" translate="no">chevron_right</span></a></div></div><div class="ds-related-work--container js-related-work-sidebar-card" data-collection-position="7" data-entity-id="59874441" data-sort-order="default"><a class="ds-related-work--title js-related-work-grid-card-title ds2-5-body-md ds2-5-body-link" href="https://www.academia.edu/59874441/Mitochondrial_dysfunction_induces_triglyceride_accumulation_in_3T3_L1_cells_role_of_fatty_acid_oxidation_and_glucose">Mitochondrial dysfunction induces triglyceride accumulation in 3T3-L1 cells: role of fatty acid -oxidation and glucose</a><div class="ds-related-work--metadata"><a class="js-related-work-grid-card-author ds2-5-body-sm ds2-5-body-link" data-author-id="44153560" href="https://independent.academia.edu/PatriciaRenard">Patricia Renard</a></div><p class="ds-related-work--metadata ds2-5-body-xs">The Journal of Lipid Research, 2005</p><div class="ds-related-work--ctas"><button class="ds2-5-text-link ds2-5-text-link--inline js-swp-download-button" data-signup-modal="{"location":"wsj-grid-card-download-pdf-modal","work_title":"Mitochondrial dysfunction induces triglyceride accumulation in 3T3-L1 cells: role of fatty acid -oxidation and glucose","attachmentId":73573074,"attachmentType":"pdf","work_url":"https://www.academia.edu/59874441/Mitochondrial_dysfunction_induces_triglyceride_accumulation_in_3T3_L1_cells_role_of_fatty_acid_oxidation_and_glucose","alternativeTracking":true}"><span class="material-symbols-outlined" style="font-size: 18px" translate="no">download</span><span class="ds2-5-text-link__content">Download free PDF</span></button><a class="ds2-5-text-link ds2-5-text-link--inline js-related-work-grid-card-view-pdf" href="https://www.academia.edu/59874441/Mitochondrial_dysfunction_induces_triglyceride_accumulation_in_3T3_L1_cells_role_of_fatty_acid_oxidation_and_glucose"><span class="ds2-5-text-link__content">View PDF</span><span class="material-symbols-outlined" style="font-size: 18px" translate="no">chevron_right</span></a></div></div><div class="ds-related-work--container js-related-work-sidebar-card" data-collection-position="8" data-entity-id="13629710" data-sort-order="default"><a class="ds-related-work--title js-related-work-grid-card-title ds2-5-body-md ds2-5-body-link" href="https://www.academia.edu/13629710/Mitochondrial_and_cellular_mechanisms_for_managing_lipid_excess">Mitochondrial and cellular mechanisms for managing lipid excess</a><div class="ds-related-work--metadata"><a class="js-related-work-grid-card-author ds2-5-body-sm ds2-5-body-link" data-author-id="36240237" href="https://independent.academia.edu/SoniaCortassa">Sonia Cortassa</a><span>, </span><a class="js-related-work-grid-card-author ds2-5-body-sm ds2-5-body-link" data-author-id="32791948" href="https://johnshopkins.academia.edu/MiguelAon">Miguel Aon</a></div><p class="ds-related-work--metadata ds2-5-body-xs">Frontiers in Physiology, 2014</p><div class="ds-related-work--ctas"><button class="ds2-5-text-link ds2-5-text-link--inline js-swp-download-button" data-signup-modal="{"location":"wsj-grid-card-download-pdf-modal","work_title":"Mitochondrial and cellular mechanisms for managing lipid excess","attachmentId":45130160,"attachmentType":"pdf","work_url":"https://www.academia.edu/13629710/Mitochondrial_and_cellular_mechanisms_for_managing_lipid_excess","alternativeTracking":true}"><span class="material-symbols-outlined" style="font-size: 18px" translate="no">download</span><span class="ds2-5-text-link__content">Download free PDF</span></button><a class="ds2-5-text-link ds2-5-text-link--inline js-related-work-grid-card-view-pdf" href="https://www.academia.edu/13629710/Mitochondrial_and_cellular_mechanisms_for_managing_lipid_excess"><span class="ds2-5-text-link__content">View PDF</span><span class="material-symbols-outlined" style="font-size: 18px" translate="no">chevron_right</span></a></div></div><div class="ds-related-work--container js-related-work-sidebar-card" data-collection-position="9" data-entity-id="106363383" data-sort-order="default"><a class="ds-related-work--title js-related-work-grid-card-title ds2-5-body-md ds2-5-body-link" href="https://www.academia.edu/106363383/Convergent_mechanisms_for_dysregulation_of_mitochondrial_quality_control_in_metabolic_disease_implications_for_mitochondrial_therapeutics">Convergent mechanisms for dysregulation of mitochondrial quality control in metabolic disease: implications for mitochondrial therapeutics</a><div class="ds-related-work--metadata"><a class="js-related-work-grid-card-author ds2-5-body-sm ds2-5-body-link" data-author-id="31297166" href="https://google.academia.edu/BaluChacko">Balu Chacko</a></div><p class="ds-related-work--metadata ds2-5-body-xs">Biochemical Society Transactions, 2013</p><div class="ds-related-work--ctas"><button class="ds2-5-text-link ds2-5-text-link--inline js-swp-download-button" data-signup-modal="{"location":"wsj-grid-card-download-pdf-modal","work_title":"Convergent mechanisms for dysregulation of mitochondrial quality control in metabolic disease: implications for mitochondrial therapeutics","attachmentId":105581235,"attachmentType":"pdf","work_url":"https://www.academia.edu/106363383/Convergent_mechanisms_for_dysregulation_of_mitochondrial_quality_control_in_metabolic_disease_implications_for_mitochondrial_therapeutics","alternativeTracking":true}"><span class="material-symbols-outlined" style="font-size: 18px" translate="no">download</span><span class="ds2-5-text-link__content">Download free PDF</span></button><a class="ds2-5-text-link ds2-5-text-link--inline js-related-work-grid-card-view-pdf" href="https://www.academia.edu/106363383/Convergent_mechanisms_for_dysregulation_of_mitochondrial_quality_control_in_metabolic_disease_implications_for_mitochondrial_therapeutics"><span class="ds2-5-text-link__content">View PDF</span><span class="material-symbols-outlined" style="font-size: 18px" translate="no">chevron_right</span></a></div></div><div class="ds-related-work--container js-related-work-sidebar-card" data-collection-position="10" data-entity-id="81190117" data-sort-order="default"><a class="ds-related-work--title js-related-work-grid-card-title ds2-5-body-md ds2-5-body-link" href="https://www.academia.edu/81190117/Cytosolic_lipid_excess_induced_mitochondrial_dysfunction_is_the_cause_or_effect_of_high_fat_diet_induced_skeletal_muscle_insulin_resistance_a_molecular_insight">Cytosolic lipid excess-induced mitochondrial dysfunction is the cause or effect of high fat diet-induced skeletal muscle insulin resistance: a molecular insight</a><div class="ds-related-work--metadata"><a class="js-related-work-grid-card-author ds2-5-body-sm ds2-5-body-link" data-author-id="71036353" href="https://independent.academia.edu/AshishWadhwani1">Ashish Wadhwani</a></div><p class="ds-related-work--metadata ds2-5-body-xs">Molecular Biology Reports, 2018</p><div class="ds-related-work--ctas"><button class="ds2-5-text-link ds2-5-text-link--inline js-swp-download-button" data-signup-modal="{"location":"wsj-grid-card-download-pdf-modal","work_title":"Cytosolic lipid excess-induced mitochondrial dysfunction is the cause or effect of high fat diet-induced skeletal muscle insulin resistance: a molecular insight","attachmentId":87321833,"attachmentType":"pdf","work_url":"https://www.academia.edu/81190117/Cytosolic_lipid_excess_induced_mitochondrial_dysfunction_is_the_cause_or_effect_of_high_fat_diet_induced_skeletal_muscle_insulin_resistance_a_molecular_insight","alternativeTracking":true}"><span class="material-symbols-outlined" style="font-size: 18px" translate="no">download</span><span class="ds2-5-text-link__content">Download free PDF</span></button><a class="ds2-5-text-link ds2-5-text-link--inline js-related-work-grid-card-view-pdf" href="https://www.academia.edu/81190117/Cytosolic_lipid_excess_induced_mitochondrial_dysfunction_is_the_cause_or_effect_of_high_fat_diet_induced_skeletal_muscle_insulin_resistance_a_molecular_insight"><span class="ds2-5-text-link__content">View PDF</span><span class="material-symbols-outlined" style="font-size: 18px" translate="no">chevron_right</span></a></div></div><div class="ds-related-work--container js-related-work-sidebar-card" data-collection-position="11" data-entity-id="26523687" data-sort-order="default"><a class="ds-related-work--title js-related-work-grid-card-title ds2-5-body-md ds2-5-body-link" href="https://www.academia.edu/26523687/Acute_or_Chronic_Upregulation_of_Mitochondrial_Fatty_Acid_Oxidation_Has_No_Net_Effect_on_Whole_Body_Energy_Expenditure_or_Adiposity">Acute or Chronic Upregulation of Mitochondrial Fatty Acid Oxidation Has No Net Effect on Whole-Body Energy Expenditure or Adiposity</a><div class="ds-related-work--metadata"><a class="js-related-work-grid-card-author ds2-5-body-sm ds2-5-body-link" data-author-id="50492081" href="https://sydney.academia.edu/AndrewHoy">Andrew Hoy</a></div><p class="ds-related-work--metadata ds2-5-body-xs">Cell Metabolism, 2010</p><div class="ds-related-work--ctas"><button class="ds2-5-text-link ds2-5-text-link--inline js-swp-download-button" data-signup-modal="{"location":"wsj-grid-card-download-pdf-modal","work_title":"Acute or Chronic Upregulation of Mitochondrial Fatty Acid Oxidation Has No Net Effect on Whole-Body Energy Expenditure or Adiposity","attachmentId":46820167,"attachmentType":"pdf","work_url":"https://www.academia.edu/26523687/Acute_or_Chronic_Upregulation_of_Mitochondrial_Fatty_Acid_Oxidation_Has_No_Net_Effect_on_Whole_Body_Energy_Expenditure_or_Adiposity","alternativeTracking":true}"><span class="material-symbols-outlined" style="font-size: 18px" translate="no">download</span><span class="ds2-5-text-link__content">Download free PDF</span></button><a class="ds2-5-text-link ds2-5-text-link--inline js-related-work-grid-card-view-pdf" href="https://www.academia.edu/26523687/Acute_or_Chronic_Upregulation_of_Mitochondrial_Fatty_Acid_Oxidation_Has_No_Net_Effect_on_Whole_Body_Energy_Expenditure_or_Adiposity"><span class="ds2-5-text-link__content">View PDF</span><span class="material-symbols-outlined" style="font-size: 18px" translate="no">chevron_right</span></a></div></div><div class="ds-related-work--container js-related-work-sidebar-card" data-collection-position="12" data-entity-id="55504942" data-sort-order="default"><a class="ds-related-work--title js-related-work-grid-card-title ds2-5-body-md ds2-5-body-link" href="https://www.academia.edu/55504942/Activity_Based_Protein_Profiling_Reveals_Mitochondrial_Oxidative_Enzyme_Impairment_and_Restoration_in_Diet_Induced_Obese_Mice">Activity-Based Protein Profiling Reveals Mitochondrial Oxidative Enzyme Impairment and Restoration in Diet-Induced Obese Mice</a><div class="ds-related-work--metadata"><a class="js-related-work-grid-card-author ds2-5-body-sm ds2-5-body-link" data-author-id="81377882" href="https://independent.academia.edu/NatalieSadler1">Natalie Sadler</a></div><p class="ds-related-work--metadata ds2-5-body-xs">PLoS ONE, 2012</p><div class="ds-related-work--ctas"><button class="ds2-5-text-link ds2-5-text-link--inline js-swp-download-button" data-signup-modal="{"location":"wsj-grid-card-download-pdf-modal","work_title":"Activity-Based Protein Profiling Reveals Mitochondrial Oxidative Enzyme Impairment and Restoration in Diet-Induced Obese Mice","attachmentId":71344212,"attachmentType":"pdf","work_url":"https://www.academia.edu/55504942/Activity_Based_Protein_Profiling_Reveals_Mitochondrial_Oxidative_Enzyme_Impairment_and_Restoration_in_Diet_Induced_Obese_Mice","alternativeTracking":true}"><span class="material-symbols-outlined" style="font-size: 18px" translate="no">download</span><span class="ds2-5-text-link__content">Download free PDF</span></button><a class="ds2-5-text-link ds2-5-text-link--inline js-related-work-grid-card-view-pdf" href="https://www.academia.edu/55504942/Activity_Based_Protein_Profiling_Reveals_Mitochondrial_Oxidative_Enzyme_Impairment_and_Restoration_in_Diet_Induced_Obese_Mice"><span class="ds2-5-text-link__content">View PDF</span><span class="material-symbols-outlined" style="font-size: 18px" translate="no">chevron_right</span></a></div></div><div class="ds-related-work--container js-related-work-sidebar-card" data-collection-position="13" data-entity-id="21840671" data-sort-order="default"><a class="ds-related-work--title js-related-work-grid-card-title ds2-5-body-md ds2-5-body-link" href="https://www.academia.edu/21840671/Impaired_mitochondrial_biogenesis_in_adipose_tissue_in_acquired_obesity">Impaired mitochondrial biogenesis in adipose tissue in acquired obesity</a><div class="ds-related-work--metadata"><a class="js-related-work-grid-card-author ds2-5-body-sm ds2-5-body-link" data-author-id="33523890" href="https://independent.academia.edu/AilaRissanen">Aila Rissanen</a></div><p class="ds-related-work--metadata ds2-5-body-xs">Diabetes, 2015</p><div class="ds-related-work--ctas"><button class="ds2-5-text-link ds2-5-text-link--inline js-swp-download-button" data-signup-modal="{"location":"wsj-grid-card-download-pdf-modal","work_title":"Impaired mitochondrial biogenesis in adipose tissue in acquired obesity","attachmentId":42586433,"attachmentType":"pdf","work_url":"https://www.academia.edu/21840671/Impaired_mitochondrial_biogenesis_in_adipose_tissue_in_acquired_obesity","alternativeTracking":true}"><span class="material-symbols-outlined" style="font-size: 18px" translate="no">download</span><span class="ds2-5-text-link__content">Download free PDF</span></button><a class="ds2-5-text-link ds2-5-text-link--inline js-related-work-grid-card-view-pdf" href="https://www.academia.edu/21840671/Impaired_mitochondrial_biogenesis_in_adipose_tissue_in_acquired_obesity"><span class="ds2-5-text-link__content">View PDF</span><span class="material-symbols-outlined" style="font-size: 18px" translate="no">chevron_right</span></a></div></div><div class="ds-related-work--container js-related-work-sidebar-card" data-collection-position="14" data-entity-id="24887211" data-sort-order="default"><a class="ds-related-work--title js-related-work-grid-card-title ds2-5-body-md ds2-5-body-link" href="https://www.academia.edu/24887211/Mitochondrial_Dysfunction_in_Type_2_Diabetes_and_Obesity">Mitochondrial Dysfunction in Type 2 Diabetes and Obesity</a><div class="ds-related-work--metadata"><a class="js-related-work-grid-card-author ds2-5-body-sm ds2-5-body-link" data-author-id="47975932" href="https://independent.academia.edu/KurtH%C3%B8jlund">Kurt Højlund</a></div><p class="ds-related-work--metadata ds2-5-body-xs">Endocrinology and Metabolism Clinics of North America, 2008</p><div class="ds-related-work--ctas"><button class="ds2-5-text-link ds2-5-text-link--inline js-swp-download-button" data-signup-modal="{"location":"wsj-grid-card-download-pdf-modal","work_title":"Mitochondrial Dysfunction in Type 2 Diabetes and Obesity","attachmentId":45207372,"attachmentType":"pdf","work_url":"https://www.academia.edu/24887211/Mitochondrial_Dysfunction_in_Type_2_Diabetes_and_Obesity","alternativeTracking":true}"><span class="material-symbols-outlined" style="font-size: 18px" translate="no">download</span><span class="ds2-5-text-link__content">Download free PDF</span></button><a class="ds2-5-text-link ds2-5-text-link--inline js-related-work-grid-card-view-pdf" href="https://www.academia.edu/24887211/Mitochondrial_Dysfunction_in_Type_2_Diabetes_and_Obesity"><span class="ds2-5-text-link__content">View PDF</span><span class="material-symbols-outlined" style="font-size: 18px" translate="no">chevron_right</span></a></div></div><div class="ds-related-work--container js-related-work-sidebar-card" data-collection-position="15" data-entity-id="56957699" data-sort-order="default"><a class="ds-related-work--title js-related-work-grid-card-title ds2-5-body-md ds2-5-body-link" href="https://www.academia.edu/56957699/Increased_Mitochondrial_Oxidative_Phosphorylation_in_the_Liver_Is_Associated_With_Obesity_and_Insulin_Resistance">Increased Mitochondrial Oxidative Phosphorylation in the Liver Is Associated With Obesity and Insulin Resistance</a><div class="ds-related-work--metadata"><a class="js-related-work-grid-card-author ds2-5-body-sm ds2-5-body-link" data-author-id="140659986" href="https://independent.academia.edu/HoppelCharles">Charles Hoppel</a></div><p class="ds-related-work--metadata ds2-5-body-xs">Obesity, 2011</p><div class="ds-related-work--ctas"><button class="ds2-5-text-link ds2-5-text-link--inline js-swp-download-button" data-signup-modal="{"location":"wsj-grid-card-download-pdf-modal","work_title":"Increased Mitochondrial Oxidative Phosphorylation in the Liver Is Associated With Obesity and Insulin Resistance","attachmentId":72090172,"attachmentType":"pdf","work_url":"https://www.academia.edu/56957699/Increased_Mitochondrial_Oxidative_Phosphorylation_in_the_Liver_Is_Associated_With_Obesity_and_Insulin_Resistance","alternativeTracking":true}"><span class="material-symbols-outlined" style="font-size: 18px" translate="no">download</span><span class="ds2-5-text-link__content">Download free PDF</span></button><a class="ds2-5-text-link ds2-5-text-link--inline js-related-work-grid-card-view-pdf" href="https://www.academia.edu/56957699/Increased_Mitochondrial_Oxidative_Phosphorylation_in_the_Liver_Is_Associated_With_Obesity_and_Insulin_Resistance"><span class="ds2-5-text-link__content">View PDF</span><span class="material-symbols-outlined" style="font-size: 18px" translate="no">chevron_right</span></a></div></div><div class="ds-related-work--container js-related-work-sidebar-card" data-collection-position="16" data-entity-id="86488505" data-sort-order="default"><a class="ds-related-work--title js-related-work-grid-card-title ds2-5-body-md ds2-5-body-link" href="https://www.academia.edu/86488505/Obesity_causes_irreversible_mitochondria_failure_in_visceral_adipose_tissue_despite_successful_anti_obesogenic_lifestyle_based_interventions">Obesity causes irreversible mitochondria failure in visceral adipose tissue despite successful anti-obesogenic lifestyle-based interventions</a><div class="ds-related-work--metadata"><a class="js-related-work-grid-card-author ds2-5-body-sm ds2-5-body-link" data-author-id="33720301" href="https://barcelona.academia.edu/PabloMGarciaRoves">Pablo M Garcia-Roves</a></div><p class="ds-related-work--metadata ds2-5-body-xs">2020</p><div class="ds-related-work--ctas"><button class="ds2-5-text-link ds2-5-text-link--inline js-swp-download-button" data-signup-modal="{"location":"wsj-grid-card-download-pdf-modal","work_title":"Obesity causes irreversible mitochondria failure in visceral adipose tissue despite successful anti-obesogenic lifestyle-based interventions","attachmentId":90930148,"attachmentType":"pdf","work_url":"https://www.academia.edu/86488505/Obesity_causes_irreversible_mitochondria_failure_in_visceral_adipose_tissue_despite_successful_anti_obesogenic_lifestyle_based_interventions","alternativeTracking":true}"><span class="material-symbols-outlined" style="font-size: 18px" translate="no">download</span><span class="ds2-5-text-link__content">Download free PDF</span></button><a class="ds2-5-text-link ds2-5-text-link--inline js-related-work-grid-card-view-pdf" href="https://www.academia.edu/86488505/Obesity_causes_irreversible_mitochondria_failure_in_visceral_adipose_tissue_despite_successful_anti_obesogenic_lifestyle_based_interventions"><span class="ds2-5-text-link__content">View PDF</span><span class="material-symbols-outlined" style="font-size: 18px" translate="no">chevron_right</span></a></div></div><div class="ds-related-work--container js-related-work-sidebar-card" data-collection-position="17" data-entity-id="15939479" data-sort-order="default"><a class="ds-related-work--title js-related-work-grid-card-title ds2-5-body-md ds2-5-body-link" href="https://www.academia.edu/15939479/Mitochondrial_Adaptations_to_Obesity_Related_Oxidant_Stress">Mitochondrial Adaptations to Obesity-Related Oxidant Stress</a><div class="ds-related-work--metadata"><a class="js-related-work-grid-card-author ds2-5-body-sm ds2-5-body-link" data-author-id="35099112" href="https://independent.academia.edu/AnnaDiehl">Anna Diehl</a></div><p class="ds-related-work--metadata ds2-5-body-xs">Archives of Biochemistry and Biophysics, 2000</p><div class="ds-related-work--ctas"><button class="ds2-5-text-link ds2-5-text-link--inline js-swp-download-button" data-signup-modal="{"location":"wsj-grid-card-download-pdf-modal","work_title":"Mitochondrial Adaptations to Obesity-Related Oxidant Stress","attachmentId":42818096,"attachmentType":"pdf","work_url":"https://www.academia.edu/15939479/Mitochondrial_Adaptations_to_Obesity_Related_Oxidant_Stress","alternativeTracking":true}"><span class="material-symbols-outlined" style="font-size: 18px" translate="no">download</span><span class="ds2-5-text-link__content">Download free PDF</span></button><a class="ds2-5-text-link ds2-5-text-link--inline js-related-work-grid-card-view-pdf" href="https://www.academia.edu/15939479/Mitochondrial_Adaptations_to_Obesity_Related_Oxidant_Stress"><span class="ds2-5-text-link__content">View PDF</span><span class="material-symbols-outlined" style="font-size: 18px" translate="no">chevron_right</span></a></div></div></div><div class="ds-related-content--container"><h2 class="ds-related-content--heading">Related topics</h2><div class="ds-research-interests--pills-container"><a class="js-related-research-interest ds-research-interests--pill" data-entity-id="54508" rel="nofollow" href="https://www.academia.edu/Documents/in/Review">Review</a><a class="js-related-research-interest ds-research-interests--pill" data-entity-id="280879" rel="nofollow" href="https://www.academia.edu/Documents/in/Mitochondrial_dysfunction">Mitochondrial dysfunction</a></div></div></div></div></div><div class="footer--content"><ul class="footer--main-links hide-on-mobile"><li><a href="https://www.academia.edu/about">About</a></li><li><a href="https://www.academia.edu/press">Press</a></li><li><a href="https://www.academia.edu/documents">Papers</a></li><li><a href="https://www.academia.edu/topics">Topics</a></li><li><a href="https://www.academia.edu/hiring"><svg style="width: 13px; height: 13px; position: relative; bottom: -1px;" aria-hidden="true" focusable="false" data-prefix="fas" data-icon="briefcase" class="svg-inline--fa fa-briefcase fa-w-16" role="img" xmlns="http://www.w3.org/2000/svg" viewBox="0 0 512 512"><path fill="currentColor" d="M320 336c0 8.84-7.16 16-16 16h-96c-8.84 0-16-7.16-16-16v-48H0v144c0 25.6 22.4 48 48 48h416c25.6 0 48-22.4 48-48V288H320v48zm144-208h-80V80c0-25.6-22.4-48-48-48H176c-25.6 0-48 22.4-48 48v48H48c-25.6 0-48 22.4-48 48v80h512v-80c0-25.6-22.4-48-48-48zm-144 0H192V96h128v32z"></path></svg> <strong>We're Hiring!</strong></a></li><li><a href="https://support.academia.edu/hc/en-us"><svg style="width: 12px; height: 12px; position: relative; bottom: -1px;" aria-hidden="true" focusable="false" data-prefix="fas" data-icon="question-circle" class="svg-inline--fa fa-question-circle fa-w-16" role="img" xmlns="http://www.w3.org/2000/svg" viewBox="0 0 512 512"><path fill="currentColor" d="M504 256c0 136.997-111.043 248-248 248S8 392.997 8 256C8 119.083 119.043 8 256 8s248 111.083 248 248zM262.655 90c-54.497 0-89.255 22.957-116.549 63.758-3.536 5.286-2.353 12.415 2.715 16.258l34.699 26.31c5.205 3.947 12.621 3.008 16.665-2.122 17.864-22.658 30.113-35.797 57.303-35.797 20.429 0 45.698 13.148 45.698 32.958 0 14.976-12.363 22.667-32.534 33.976C247.128 238.528 216 254.941 216 296v4c0 6.627 5.373 12 12 12h56c6.627 0 12-5.373 12-12v-1.333c0-28.462 83.186-29.647 83.186-106.667 0-58.002-60.165-102-116.531-102zM256 338c-25.365 0-46 20.635-46 46 0 25.364 20.635 46 46 46s46-20.636 46-46c0-25.365-20.635-46-46-46z"></path></svg> <strong>Help Center</strong></a></li></ul><ul class="footer--research-interests"><li>Find new research papers in:</li><li><a href="https://www.academia.edu/Documents/in/Physics">Physics</a></li><li><a href="https://www.academia.edu/Documents/in/Chemistry">Chemistry</a></li><li><a href="https://www.academia.edu/Documents/in/Biology">Biology</a></li><li><a href="https://www.academia.edu/Documents/in/Health_Sciences">Health Sciences</a></li><li><a href="https://www.academia.edu/Documents/in/Ecology">Ecology</a></li><li><a href="https://www.academia.edu/Documents/in/Earth_Sciences">Earth Sciences</a></li><li><a href="https://www.academia.edu/Documents/in/Cognitive_Science">Cognitive Science</a></li><li><a href="https://www.academia.edu/Documents/in/Mathematics">Mathematics</a></li><li><a href="https://www.academia.edu/Documents/in/Computer_Science">Computer Science</a></li></ul><ul class="footer--legal-links hide-on-mobile"><li><a href="https://www.academia.edu/terms">Terms</a></li><li><a href="https://www.academia.edu/privacy">Privacy</a></li><li><a href="https://www.academia.edu/copyright">Copyright</a></li><li>Academia ©2025</li></ul></div> </body> </html>