Circadian Gating of Thyroid Hormone Action in Hepatocytes

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usa-input-error-message selection-validation-message"> Name must be less than 100 characters </div> </div> <div class="action-panel-control-wrap existing-collections-controls"> <label for="collections-action-panel-add-to-existing" class="action-panel-label"> Choose a collection: </label> <select id="collections-action-panel-add-to-existing" class="action-panel-selector collections-action-add-to-existing" data-ga-category="save_share" data-ga-action="select_collection" data-ga-label="($('#collections-action-add-to-existing').val() === 'Favorites') ? 'Favorites' : 'non_favorites_collection'"> </select> <div class="collections-retry-load-on-error usa-input-error-message selection-validation-message"> Unable to load your collection due to an error<br> <a href="#">Please try again</a> </div> </div> </div> <div class="action-panel-actions"> <button class="action-panel-submit" type="submit" data-loading-label="Adding..." data-pinger-ignore data-ga-category="save_share" data-ga-action="collections" data-ga-label="add"> Add </button> <button class="action-panel-cancel" aria-label="Close 'Add to Collections' panel" ref="linksrc=close_collections_panel" aria-controls="collections-action-panel" aria-expanded="false" data-ga-category="save_share" data-ga-action="collections" data-ga-label="cancel"> Cancel </button> </div> </form> </div> </div> <div id="bibliography-action-panel" class="bibliography-action-panel action-panel in-progress-dots-panel" aria-hidden="true" data-bibliography-open-panel-enabled="false" data-bibliography-open-panel-url-hash="#open-bibliography-panel"> <div class="inner-wrap"> <h3 class="action-panel-heading"> Add to My Bibliography </h3> <form id="bibliography-action-panel-form" class="bibliography-action-panel-form action-panel-content action-form action-panel-smaller-selectors" data-add-to-bibliography-max-amount="100" data-add-to-bibliography-batch-size="10" data-bibliography-delegates-url="/list-bibliography-delegates/" data-add-to-bibliography-url="/add-to-bibliography/" data-get-article-ids-by-search-url="/get-article-ids-by-search/" data-mybib-root-url="https://www.ncbi.nlm.nih.gov/myncbi/collections/mybibliography/"> <input type="hidden" name="csrfmiddlewaretoken" value="sdNuDQ37FTSuXILvCCx8K0TeORl8f0YUGLZFc67NvpPoALY4B1MXMsxs0mDU8jww"> <div class="action-panel-control-wrap bibliographies-controls"> <div class="choice-group"> <ul class="bibliographies-action-add radio-group-items"> <li> <input name="bibliography" id="my-bibliography" class="my-bibliography" type="radio" checked/> <label for="my-bibliography">My Bibliography</label> </li> </ul> </div> </div> <div class="bibliographies-retry-load-on-error usa-input-error-message selection-validation-message"> Unable to load your delegates due to an error<br> <a href="#">Please try again</a> </div> <div class="action-panel-actions"> <button class="action-panel-submit" type="submit" data-loading-label="Adding..." data-pinger-ignore> Add </button> <button class="action-panel-cancel" aria-label="Close 'Add to bibliography' panel" ref="linksrc=close_bibliography_panel" aria-controls="bibliography-action-panel" aria-expanded="false" data-ga-category="save_share" data-ga-action="mybib" data-ga-label="cancel"> Cancel </button> </div> </form> </div> </div> <div id="saved-search-action-panel" class="saved-search-action-panel action-panel " aria-hidden="true" data-saved-search-open-panel-enabled="false" data-saved-search-open-panel-url-hash="#open-saved-search-panel"> <div class="inner-wrap"> <h2 class="action-panel-heading"> Your saved search </h2> <form id="saved-search-action-panel-form" class="saved-search-action-panel-form action-panel-content action-form" data-create-saved-search-url="/create-saved-search/" data-try-search-terms-url="/try-search-term/" data-saved-search-root-url="https://www.ncbi.nlm.nih.gov/myncbi/searches/"> <input type="hidden" name="csrfmiddlewaretoken" value="sdNuDQ37FTSuXILvCCx8K0TeORl8f0YUGLZFc67NvpPoALY4B1MXMsxs0mDU8jww"> <div class="action-panel-control-wrap"> <label for="saved-search-name" class="action-panel-label saved-search-name-label required-field-asterisk"> Name of saved search: </label> <input maxlength="200" type="text" name="saved-search-name" id="saved-search-name" class="saved-search-name" value="" required pattern="[^"&=<>\/]*" title="The following characters are not allowed in the Name field: "&=<>/"> </div> <div class="action-panel-control-wrap"> <label for="saved-search-term" class="action-panel-label required-field-asterisk"> Search terms: </label> <textarea name="saved-search-term" id="saved-search-term" class="saved-search-term" required></textarea> </div> <div class="test-search-term-wrap"> <a href="#" class="try-search-term">Test search terms</a> </div> <div class="choice-group action-panel-extra-margin-top"> <span class="action-panel-label" id="fieldset-label"> Would you like email updates of new search results? </span> <fieldset id="saved-search-alert" aria-describedby="fieldset-label"> <legend class="usa-sr-only">Saved Search Alert Radio Buttons</legend> <ul class="radio-group-items"> <li> <input type="radio" id="saved-search-alert-yes" class="saved-search-alert-yes" name="saved-search-alert" value="yes" checked> <label for="saved-search-alert-yes" class="action-panel-label">Yes</label> </li> <li> <input aria-label="No radio input" type="radio" id="saved-search-alert-no" class="saved-search-alert-no" name="saved-search-alert" value="no"> <label for="saved-search-alert-no" class="action-panel-label">No</label> </li> </ul> </fieldset> </div> <div class="alert-schedule-wrap"> <div class="action-panel-control-wrap"> <label class="action-panel-label"> Email: </label> <span aria-label="Email address" id="saved-search-email" class="action-panel-label"><span class="action-panel-label-bold"></span> (<a class="myncbi-account-settings" href="https://www.ncbi.nlm.nih.gov/account/settings/">change</a>)</span> </div> <div class="action-panel-control-wrap action-panel-extra-margin-top"> <label for="saved-search-frequency" class="action-panel-label"> Frequency: </label> <select id="saved-search-frequency" class="no-border-panel-selector saved-search-frequency"> <option value="monthly">Monthly</option> <option value="weekly">Weekly</option> <option value="daily">Daily</option> </select> </div> <div class="action-panel-control-wrap saved-search-monthly-additional"> <label for="saved-search-monthly-on-day" class="action-panel-label"> Which day? </label> <select id="saved-search-monthly-on-day" class="no-border-panel-selector"> <option value="Sunday">The first Sunday</option> <option value="Monday">The first Monday</option> <option value="Tuesday">The first Tuesday</option> <option value="Wednesday">The first Wednesday</option> <option value="Thursday">The first Thursday</option> <option value="Friday">The first Friday</option> <option value="Saturday">The first Saturday</option> <option value="day">The first day</option> <option value="weekday">The first weekday</option> </select> </div> <div class="action-panel-control-wrap saved-search-weekly-additional"> <label for="saved-search-weekly-on-day" class="action-panel-label"> Which day? </label> <select id="saved-search-weekly-on-day" class="no-border-panel-selector saved-search-weekly-on-day"> <option value="Sunday">Sunday</option> <option value="Monday">Monday</option> <option value="Tuesday">Tuesday</option> <option value="Wednesday">Wednesday</option> <option value="Thursday">Thursday</option> <option value="Friday">Friday</option> <option value="Saturday">Saturday</option> </select> </div> <div class="action-panel-control-wrap"> <label for="saved-search-report" class="action-panel-label"> Report format: </label> <select id="saved-search-report" class="no-border-panel-selector saved-search-report"> <option value="DocSum">Summary</option> <option value="DocSumText">Summary (text)</option> <option value="Abstract">Abstract</option> <option value="AbstractText">Abstract (text)</option> <option value="MEDLINE">PubMed</option> </select> </div> <div class="action-panel-control-wrap"> <label for="saved-search-amount" class="action-panel-label"> Send at most: </label> <select id="saved-search-amount" class="no-border-panel-selector saved-search-amount"> <option value="1">1 item</option> <option value="5" selected>5 items</option> <option value="10">10 items</option> <option value="20">20 items</option> <option value="50">50 items</option> <option value="100">100 items</option> <option value="200">200 items</option> </select> </div> <div> <input type="checkbox" id="saved-search-send-if-no-result" class="saved-search-send-if-no-result" name="saved-search-send-if-no-result"> <label for="saved-search-send-if-no-result" class="action-panel-label smaller-checkbox"> Send even when there aren't any new results </label> </div> <div class="action-panel-control-wrap option-text-in-email-wrap"> <label for="saved-search-email-text" class="action-panel-label"> Optional text in email: </label> <textarea name="saved-search-email-text" id="saved-search-email-text" class="saved-search-email-text"></textarea> </div> </div> <div class="action-panel-actions"> <button class="action-panel-submit" type="submit" data-loading-label="Saving..." data-ga-category="save_share" data-ga-action="alert" data-ga-label="save"> Save </button> <button class="action-panel-cancel" aria-label="Close 'Your saved search' panel" ref="linksrc=close_saved_search_panel" aria-controls="saved-search-action-panel" aria-expanded="false" data-ga-category="save_share" data-ga-action="alert" data-ga-label="cancel"> Cancel </button> </div> </form> </div> </div> <div id="citation-manager-action-panel" class="citation-manager-action-panel action-panel" aria-hidden="true"> <div class="inner-wrap"> <h2 class="action-panel-heading"> Create a file for external citation management software </h2> <form id="citation-manager-action-panel-form" class="action-panel-content action-form" action="/results-export-ids/" data-by-search-action="/results-export-search-data/" data-by-ids-action="/results-export-ids/" method="post" data-by-search-method="post" data-by-ids-method="post"> <input type="hidden" name="csrfmiddlewaretoken" value="sdNuDQ37FTSuXILvCCx8K0TeORl8f0YUGLZFc67NvpPoALY4B1MXMsxs0mDU8jww"> <input name="results-format" type="hidden" value="pubmed"/> <div class="action-panel-actions"> <button class="action-panel-submit" type="submit" data-loading-label="Sending..." data-ga-category="save_share" data-ga-action="citation_manager" data-ga-label="save"> Create file </button> <button class="action-panel-cancel" aria-label="Close 'Send citations to citation manager' panel" ref="linksrc=close_citation_manager_panel" aria-controls="citation-manager-action-panel" aria-expanded="false" data-ga-category="save_share" data-ga-action="citation_manager" data-ga-label="cancel"> Cancel </button> </div> </form> </div> </div> <div id="rss-action-panel" class="rss-action-panel action-panel " aria-hidden="true"> <div class="inner-wrap"> <h2 class="action-panel-heading"> Your RSS Feed </h2> <form id="rss-action-panel-form" class="rss-action-panel-form action-panel-content action-form" data-create-rss-feed-url="/create-rss-feed-url/" data-search-form-term-value=""> <input type="hidden" name="csrfmiddlewaretoken" value="sdNuDQ37FTSuXILvCCx8K0TeORl8f0YUGLZFc67NvpPoALY4B1MXMsxs0mDU8jww"> <div class="action-panel-control-wrap"> <label for="rss-name" class="action-panel-label required-field-asterisk"> Name of RSS Feed: </label> <input maxlength="200" placeholder="Name" type="text" name="rss-name" id="rss-name" class="rss-name" value='' required pattern="[^"&=<>\/]*" title="The following characters are not allowed in the Name field: "&=<>/"> </div> <div class="rss-limit-wrap"> <div class="action-panel-control-wrap action-panel-extra-margin-top"> <label for="rss-limit" class="action-panel-label"> Number of items displayed: </label> <select id="rss-limit" class="no-border-panel-selector rss-limit"> <option value="5">5</option> <option value="10">10</option> <option value="15" selected="selected">15</option> <option value="20">20</option> <option value="50">50</option> <option value="100">100</option> </select> </div> </div> <div class="action-panel-actions"> <button class="action-panel-submit" type="submit" data-loading-label="Creating..." data-ga-category="save_share" data-ga-action="alert" data-ga-label="save"> Create RSS </button> <button class="action-panel-cancel" aria-label="Close 'Your RSS' panel" ref="linksrc=close_rss_panel" aria-controls="rss-action-panel" aria-expanded="false" data-ga-category="save_share" data-ga-action="alert" data-ga-label="cancel"> Cancel </button> </div> <div class="action-panel-control-wrap rss-link-copy-wrap"> <label for="rss-link" class="usa-sr-only">RSS Link</label> <input placeholder="Your RSS Feed Link" type="text" name="rss-link" id="rss-link" class="rss-link" title="RSS Link"> <button type="button" disabled class="rss-link-copy-button disabled" data-ga-category="save_share" data-ga-action="rss" data-ga-label="copy"> Copy </button> </div> </form> </div> </div> </div> </div> <div class="article-page" id="article-page" data-article-pmid="38920666"> <aside class="page-sidebar"> <div class="inner-wrap"> <div class="full-text-links"> <div class="full-view"> <h3 class="title"> Full text links </h3> <div class="full-text-links-list"> <a class="link-item dialog-focus" href="https://www.mdpi.com/resolver?pii=cells13121038" target="_blank" rel="noopener" ref="linksrc=fulltextorjournal_fulltext&is_pmc=False&PrId=6383&itool=Abstract-def&log$=linkouticon&uid=38920666&db=pubmed&nlmid=101600052" title="See full text options at MDPI" data-ga-category="full_text" data-ga-action="MDPI" data-ga-label="38920666" ><img src="https://cdn.ncbi.nlm.nih.gov/corehtml/query/egifs/https:--res.mdpi.com-data-pubmed-linkout.png" alt="MDPI full text link"><span class="text"> MDPI </span></a><a class="link-item pmc " href="https://pmc.ncbi.nlm.nih.gov/articles/pmid/38920666/" target="_blank" rel="noopener" ref="linksrc=fulltextorjournal_fulltext&is_pmc=True&PrId=3494&itool=Abstract-def&log$=linkouticon&uid=38920666&db=pubmed&nlmid=101600052" title="Free full text at PubMed Central" data-ga-category="full_text" data-ga-action="PMC" data-ga-label="38920666" ><span class="text"> Free PMC article </span></a> </div> </div> <div class="short-view"> <a href="#" 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value="sdNuDQ37FTSuXILvCCx8K0TeORl8f0YUGLZFc67NvpPoALY4B1MXMsxs0mDU8jww"><div class="choice-group" role="radiogroup"><ul class="radio-group-items"><li><input type="radio" id="collections-action-dialog-new" class="collections-new" name="collections" value="new" data-ga-category="collections_button" data-ga-action="click" data-ga-label="collections_radio_new"><label for="collections-action-dialog-new">Create a new collection</label></li><li><input type="radio" id="collections-action-dialog-existing" class="collections-existing" name="collections" value="existing" checked="true" data-ga-category="collections_button" data-ga-action="click" data-ga-label="collections_radio_existing"><label for="collections-action-dialog-existing">Add to an existing collection</label></li></ul></div><div class="controls-wrapper"><div class="action-panel-control-wrap new-collections-controls"><label for="collections-action-dialog-add-to-new" class="action-panel-label required-field-asterisk"> Name your collection: </label><input type="text" name="add-to-new-collection" id="collections-action-dialog-add-to-new" class="collections-action-add-to-new" pattern="[^"&=<>\/]*" title="The following characters are not allowed in the Name field: "&=<>/" maxlength="100" data-ga-category="collections_button" data-ga-action="create_collection" data-ga-label="non_favorties_collection"><div class="collections-new-name-too-long usa-input-error-message selection-validation-message"> Name must be less than 100 characters </div></div><div class="action-panel-control-wrap existing-collections-controls"><label for="collections-action-dialog-add-to-existing" class="action-panel-label"> Choose a collection: </label><select id="collections-action-dialog-add-to-existing" class="action-panel-selector collections-action-add-to-existing" data-ga-category="collections_button" data-ga-action="select_collection" data-ga-label="($('.collections-action-add-to-existing').val() === 'Favorites') ? 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data-ga-category="search" data-ga-action="author_link" data-ga-label="Leonardo Vinicius Monteiro de Assis">Leonardo Vinicius Monteiro de Assis</a><sup class="affiliation-links"><span class="author-sup-separator"> </span><a class="affiliation-link" title="Institute of Neurobiology, Center of Brain Behavior & Metabolism, University of Lübeck, 23562 Lübeck, Germany." href="#short-view-affiliation-1" ref="linksrc=author_aff"> 1 </a><span class="author-sup-separator"> </span><a class="affiliation-link" title="University Hospital Schleswig-Holstein, Campus Lübeck, 23538 Lübeck, Germany." href="#short-view-affiliation-2" ref="linksrc=author_aff"> 2 </a></sup></span> </div> </div> <div class="affiliations"> <h3 class="title"> Affiliations </h3> <ul class="item-list"> <li data-affiliation-id="short-view-affiliation-1" id="short-view-affiliation-1" ><sup class="key">1</sup> Institute of Neurobiology, Center of Brain Behavior & Metabolism, University of Lübeck, 23562 Lübeck, Germany.</li> <li data-affiliation-id="short-view-affiliation-2" id="short-view-affiliation-2" ><sup class="key">2</sup> University Hospital Schleswig-Holstein, Campus Lübeck, 23538 Lübeck, Germany.</li> </ul> </div> </div> <ul class="identifiers" id="short-view-identifiers"> <li> <span class="identifier pubmed"> <span class="id-label"> PMID: </span> <strong class="current-id" title="PubMed ID">38920666</strong> </span> </li> <li> <span class="identifier pmc"> <span class="id-label"> PMCID: </span> <a class="id-link" target="_blank" rel="noopener" ref="linksrc=article_id_link&article_id=PMC11202020&id_type=PMC" href="https://pmc.ncbi.nlm.nih.gov/articles/PMC11202020/" data-ga-category="full_text" data-ga-action="PMCID" > PMC11202020 </a> </span> </li> <li> <span class="identifier doi"> <span class="id-label"> DOI: </span> <a class="id-link" target="_blank" rel="noopener" ref="linksrc=article_id_link&article_id=10.3390/cells13121038&id_type=DOI" href="https://doi.org/10.3390/cells13121038" 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data-default-format-value="abstract" data-current-format-value="abstract" role="region"><button class="trigger usa-button" title="Change format" data-ga-category="display_options" data-ga-action="display_options_dialog"><span class="button-label">Display options</span></button><div class="dropdown" hidden><div class="title"> Display options </div><div class="content"><div class="format-container"><span class="option-label"> Format </span><select name="format" data-initial-value="abstract" aria-label="Display format" id="inline-actions-display-format"><option value="abstract">Abstract</option><option value="pubmed">PubMed</option><option value="pmid">PMID</option></select></div></div></div></div></div></div> <div class="abstract" id="abstract"> <h2 class="title"> Abstract </h2> <div class="abstract-content selected" id="eng-abstract"> <p> Thyroid hormones, thyroxin (T<sub>4</sub>) and the biologically active triiodothyronine (T<sub>3</sub>), play important roles in liver metabolic regulation, including fatty acid biosynthesis, beta-oxidation, and cholesterol homeostasis. These functions position TH signaling as a potential target for the treatment of metabolic dysfunction-associated steatotic liver disease (MASLD). Elevated T<sub>3</sub> levels in the circulation are associated with increased hepatic lipid turnover, which is also under the control of the circadian clock system. In this study, we developed a cell system to study the impact of hepatocyte circadian rhythms on the metabolic response to T<sub>3</sub> treatment under control and steatotic conditions. Synchronized AML-12 circadian reporter hepatocytes were treated with T<sub>3</sub> at different circadian phases and metabolic conditions. T<sub>3</sub> treatment increased metabolic activity in a dose-independent fashion and had no significant effect on circadian rhythms in AML-12 cells. T<sub>3</sub> had marked time-of-treatment-dependent effects on metabolic transcript expression. Steatosis induction altered metabolic transcript expression in AML-12 cells. In this condition, the circadian rhythm period was lengthened, and this effect was independent of T<sub>3</sub>. Under steatotic conditions, T<sub>3</sub> had marked time-of-treatment dependent effects on metabolic transcript expression, which differed from those observed under control conditions. These findings reveal a time-of-day-dependent response of hepatocytes to T<sub>3</sub>, which is further modulated by the metabolic state. Our data suggest that time has a strong influence on liver TH action, which might be considered when treating MASLD. </p> </div> <p> <strong class="sub-title"> Keywords: </strong> circadian clock; endocrinology; fatty liver; lipid metabolism; thyroid hormones. </p> </div> <p class="disclaimer" id="disclaimer"> <a href="/disclaimer/" target="_blank" data-ga-category="literature_resources" data-ga-action="disclaimer_link" data-ga-label="under_abstract">PubMed Disclaimer</a> </p> <div class="conflict-of-interest" id="conflict-of-interest"> <h2 class="title"> Conflict of interest statement </h2> <div class="statement"> <p xmlns:xlink="http://www.w3.org/1999/xlink" xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:p1="http://pubmed.gov/pub-one">The authors declare no conflicts of interest.</p> </div> </div> <div class="figures" id="figures"> <h2 class="title"> Figures </h2> <div class="figures-list" id="slides-container" itemscope itemtype="http://schema.org/ImageGallery"> <figure class="figure-item " itemscope itemtype="http://schema.org/ImageObject" itemprop="associatedMedia" data-slide-index="0" data-label-slug="figure-1"> <a class="figure-link" href="https://cdn.ncbi.nlm.nih.gov/pmc/blobs/289b/11202020/00a4e9e43b6d/cells-13-01038-g001.jpg" itemprop="contentUrl" aria-describedby="figure-caption-0" role="button" data-image-width="723" data-image-height="957" data-image-alt="Figure 1" data-pmc-id="PMC11202020" data-figure-id="cells-13-01038-f001"> <img class="figure-thumb" itemprop="thumbnail" id="article-image-0" src="https://cdn.ncbi.nlm.nih.gov/pmc/blobs/289b/11202020/3047523245bc/cells-13-01038-g001.gif" alt="Figure 1" /> </a> <meta itemprop="width" itemtype="http://schema.org/ImageObject" content="723"> <meta itemprop="height" itemtype="http://schema.org/ImageObject" content="957"> <div class="figure-caption figure-caption-text" itemtype="http://schema.org/ImageObject" itemprop="caption" aria-hidden="true"> <div class="caption-wrap"> <strong class="figure-label"> <p> Figure 1 </p> </strong> <div class="figure-caption-contents"><p> Effects of T <sub> 3 </sub> on… </p></div> </div> </div> <div class="figure-caption-medium figure-caption-text" aria-hidden="true"> <strong class="figure-label"> <p> Figure 1 </p> </strong> <div class="figure-caption-contents"><p> Effects of T <sub> 3 </sub> on hepatocyte metabolism and gene regulation. ( <b> A </b> –… </p></div> </div> <figcaption id="figure-caption-0" class="figure-caption-full figure-caption-text" itemtype="http://schema.org/ImageObject" itemprop="description"> <strong class="figure-label"> Figure 1 </strong> <div class="figure-caption-contents">Effects of T<sub>3</sub> on hepatocyte metabolism and gene regulation. (<b>A</b>–<b>C</b>) Analysis of metabolic activity using XTT assay and expression levels of thyroid hormone-responsive genes (non-log transformed), <i>Thrsp</i> and <i>Thrb</i> (n = 6 per group). (<b>D</b>–<b>H</b>) Evaluation of <i>Bmal1:Luc</i> bioluminescence rhythm parameters in response to increasing concentration of T<sub>3</sub> (n = 6–10 samples per group). Boxplots show the median, mean (+), quartiles, maximum, and minimum expression values. * Represents one-way ANOVA followed by two-stage linear step-up procedure of Benjamini, Krieger, and Yekutieli post-test against the control group. * <i>q</i> < 0.05 and ** <i>q</i> < 0.01.</div> </figcaption> </figure> <figure class="figure-item " itemscope itemtype="http://schema.org/ImageObject" itemprop="associatedMedia" data-slide-index="1" data-label-slug="figure-2"> <a class="figure-link" href="https://cdn.ncbi.nlm.nih.gov/pmc/blobs/289b/11202020/001c957a2451/cells-13-01038-g002.jpg" itemprop="contentUrl" aria-describedby="figure-caption-1" role="button" data-image-width="788" data-image-height="708" data-image-alt="Figure 2" data-pmc-id="PMC11202020" data-figure-id="cells-13-01038-f002"> <img class="figure-thumb" itemprop="thumbnail" id="article-image-1" src="https://cdn.ncbi.nlm.nih.gov/pmc/blobs/289b/11202020/6a4322e9fbb4/cells-13-01038-g002.gif" alt="Figure 2" /> </a> <meta itemprop="width" itemtype="http://schema.org/ImageObject" content="788"> <meta itemprop="height" itemtype="http://schema.org/ImageObject" content="708"> <div class="figure-caption figure-caption-text" itemtype="http://schema.org/ImageObject" itemprop="caption" aria-hidden="true"> <div class="caption-wrap"> <strong class="figure-label"> <p> Figure 2 </p> </strong> <div class="figure-caption-contents"><p> Temporal dynamics of gene expression… </p></div> </div> </div> <div class="figure-caption-medium figure-caption-text" aria-hidden="true"> <strong class="figure-label"> <p> Figure 2 </p> </strong> <div class="figure-caption-contents"><p> Temporal dynamics of gene expression in response to T <sub> 3 </sub> treatment. ( <b> A… </b> </p></div> </div> <figcaption id="figure-caption-1" class="figure-caption-full figure-caption-text" itemtype="http://schema.org/ImageObject" itemprop="description"> <strong class="figure-label"> Figure 2 </strong> <div class="figure-caption-contents">Temporal dynamics of gene expression in response to T<sub>3</sub> treatment. (<b>A</b>) Illustration detailing the experimental design to investigate the effect of T<sub>3</sub> on hepatocytes under control conditions. (<b>B</b>–<b>G</b>) Sequential depiction of alterations in gene expression following administration of 100 nM T<sub>3</sub> at two time points. Fold change (non-log transformed) is shown against the BSA group (n = 3–4). Boxplots show the median, mean (+), quartiles, maximum, and minimum expression values. Comparison between time point 8 h and 20 h in T<sub>3</sub>-treated groups was performed using an unpaired Student’s <i>t</i>-test. Significance levels are as follows: * <i>p</i> < 0.05, ** <i>p</i> < 0.01, *** <i>p</i> < 0.001.</div> </figcaption> </figure> <figure class="figure-item " itemscope itemtype="http://schema.org/ImageObject" itemprop="associatedMedia" data-slide-index="2" data-label-slug="figure-3"> <a class="figure-link" href="https://cdn.ncbi.nlm.nih.gov/pmc/blobs/289b/11202020/6c315ab8b5b5/cells-13-01038-g003.jpg" itemprop="contentUrl" aria-describedby="figure-caption-2" role="button" data-image-width="748" data-image-height="927" data-image-alt="Figure 3" data-pmc-id="PMC11202020" data-figure-id="cells-13-01038-f003"> <img class="figure-thumb" itemprop="thumbnail" id="article-image-2" src="https://cdn.ncbi.nlm.nih.gov/pmc/blobs/289b/11202020/2722158a5671/cells-13-01038-g003.gif" alt="Figure 3" /> </a> <meta itemprop="width" itemtype="http://schema.org/ImageObject" content="748"> <meta itemprop="height" itemtype="http://schema.org/ImageObject" content="927"> <div class="figure-caption figure-caption-text" itemtype="http://schema.org/ImageObject" itemprop="caption" aria-hidden="true"> <div class="caption-wrap"> <strong class="figure-label"> <p> Figure 3 </p> </strong> <div class="figure-caption-contents"><p> Impact of T <sub> 3 </sub> on… </p></div> </div> </div> <div class="figure-caption-medium figure-caption-text" aria-hidden="true"> <strong class="figure-label"> <p> Figure 3 </p> </strong> <div class="figure-caption-contents"><p> Impact of T <sub> 3 </sub> on hepatic steatosis and circadian rhythms. ( <b> A </b> ,… </p></div> </div> <figcaption id="figure-caption-2" class="figure-caption-full figure-caption-text" itemtype="http://schema.org/ImageObject" itemprop="description"> <strong class="figure-label"> Figure 3 </strong> <div class="figure-caption-contents">Impact of T<sub>3</sub> on hepatic steatosis and circadian rhythms. (<b>A</b>,<b>B</b>) Visualization and quantification of lipid accumulation using oil red O (ORO) staining following treatment with 100 nM T<sub>3</sub> in cells treated with palmitate. Scale bar represents 100 μm (n = 5–6 per group). In (<b>B</b>), * represents two-way ANOVA followed by two-stage linear step-up procedure of Benjamini, Krieger, and Yekutieli test against the control group. * <i>q</i> < 0.05, **** <i>q</i> < 0.0001. (<b>C</b>–<b>H</b>) Quantitative PCR analysis depicting gene expression (non-log transformed) profiles under control (BSA-treated) and palmitate-loaded conditions, 20 h after synchronization. Unpaired <i>t</i>-test was performed, and significance is denoted as * <i>p</i> < 0.05 and ** <i>p</i> < 0.01. (<b>I</b>–<b>K</b>) Representative <i>Bmal1:luc</i> bioluminescence tracers and rhythm parameters quantification (n = 7–8). * represents two-way ANOVA followed by two-stage linear step-up procedure of Benjamini, Krieger, and Yekutieli post-test against the control group (* <i>q</i> < 0.05). Boxplots show the median, mean (+), quartiles, maximum, and minimum expression values.</div> </figcaption> </figure> <figure class="figure-item " itemscope itemtype="http://schema.org/ImageObject" itemprop="associatedMedia" data-slide-index="3" data-label-slug="figure-4"> <a class="figure-link" href="https://cdn.ncbi.nlm.nih.gov/pmc/blobs/289b/11202020/e9b696ff88ba/cells-13-01038-g004.jpg" itemprop="contentUrl" aria-describedby="figure-caption-3" role="button" data-image-width="773" data-image-height="587" data-image-alt="Figure 4" data-pmc-id="PMC11202020" data-figure-id="cells-13-01038-f004"> <img class="figure-thumb" itemprop="thumbnail" id="article-image-3" src="https://cdn.ncbi.nlm.nih.gov/pmc/blobs/289b/11202020/e41d809af8df/cells-13-01038-g004.gif" alt="Figure 4" /> </a> <meta itemprop="width" itemtype="http://schema.org/ImageObject" content="773"> <meta itemprop="height" itemtype="http://schema.org/ImageObject" content="587"> <div class="figure-caption figure-caption-text" itemtype="http://schema.org/ImageObject" itemprop="caption" aria-hidden="true"> <div class="caption-wrap"> <strong class="figure-label"> <p> Figure 4 </p> </strong> <div class="figure-caption-contents"><p> Temporal analysis of T <sub> 3… </sub> </p></div> </div> </div> <div class="figure-caption-medium figure-caption-text" aria-hidden="true"> <strong class="figure-label"> <p> Figure 4 </p> </strong> <div class="figure-caption-contents"><p> Temporal analysis of T <sub> 3 </sub> treatment effects on gene expression in hepatocytes under… </p></div> </div> <figcaption id="figure-caption-3" class="figure-caption-full figure-caption-text" itemtype="http://schema.org/ImageObject" itemprop="description"> <strong class="figure-label"> Figure 4 </strong> <div class="figure-caption-contents">Temporal analysis of T<sub>3</sub> treatment effects on gene expression in hepatocytes under steatosis. (<b>A</b>–<b>F</b>) Graphical representation of gene expression changes in response to 100 nM T<sub>3</sub> treatment across different times of the day in cell treatment with palmitate (n = 3–4 per group). Boxplots show the median, mean (+), quartiles, maximum, and minimum expression values. Fold change (non-log transformed) is shown against the palmitate group. Comparison between time point 8 h and 20 h in T<sub>3</sub>-treated groups was performed using an unpaired Student’s <i>t</i>-test. Significance levels are as follows: ** <i>p</i> < 0.01, **** <i>p</i> < 0.0001. The arrow’s direction represents an increased or decreased expression between BSA and palmitate groups treated with T<sub>3</sub> using two-way ANOVA followed by two-stage linear step-up procedure of Benjamini, Krieger, and Yekutieli post-test (<i>q</i> < 0.05).</div> </figcaption> </figure> </div>  <div class="pswp figures-dialog" id="figures-dialog" tabindex="-1" role="dialog" aria-hidden="true" data-image-gallery-uid="article-figures" aria-label="Figures Dialog">  <div class="pswp__bg"></div>  <div class="pswp__scroll-wrap">  <div class="pswp__container"> <div class="pswp__item"></div> <div class="pswp__item"></div> <div class="pswp__item"></div> </div>  <div class="pswp__ui pswp__ui--hidden"> <div class="pswp__top-bar">  <div class="pswp__counter"></div> <button class="pswp__button pswp__button--close" title="Close (Esc)"></button> <button class="pswp__button pswp__button--share" title="Share"></button> <button class="pswp__button pswp__button--fs" title="Toggle fullscreen"></button> <button class="pswp__button pswp__button--zoom" title="Zoom in/out"></button>   <div class="pswp__preloader"> <div class="pswp__preloader__icn"> <div class="pswp__preloader__cut"> <div class="pswp__preloader__donut"></div> </div> </div> </div> </div> <div class="pswp__share-modal pswp__share-modal--hidden pswp__single-tap"> <div class="pswp__share-tooltip"></div> </div> <button class="pswp__button pswp__button--arrow--left" title="Previous (arrow left)"> </button> <button class="pswp__button pswp__button--arrow--right" title="Next (arrow right)"> </button> <div class="pswp__caption"> <div class="pswp__caption__center"></div> </div> </div> </div> </div> <div class="figure-dialog-caption"> <div class="figure-caption-link-container"> <a class="figure-caption-link" href="#">See this image and copyright information in PMC</a> </div> <div class="figure-caption-center" data-expand-title="click to show full caption" data-collapse-title="click to hide full caption"> </div> <button class="figure-caption-toggle-btn" aria-label="show full caption" data-expand-text="show full caption" data-collapse-text="hide full caption">  </button> </div> </div> <div class="similar-articles" id="similar"> <h2 class="title"> Similar articles </h2> <ul class="articles-list" id="similar-articles-list"> <li class="full-docsum"> <div class="docsum-content" style="display:inline;"> <a class="docsum-title" href="/36137063/" ref="article_id=36137063&linksrc=similar_articles_link&ordinalpos=1" data-ga-category="similar_article" data-ga-action="36137063" data-ga-label=""> Depressing time: Waiting, melancholia, and the psychoanalytic practice of care. </a> <div class="docsum-citation full-citation"> <span class="docsum-authors full-authors">Salisbury L, Baraitser L.</span> <span class="docsum-authors short-authors">Salisbury L, et al.</span> <span class="docsum-journal-citation full-journal-citation">In: Kirtsoglou E, Simpson B, editors. 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metabolism"> Search in PubMed </a></li><li><a class="search-in-mesh-link dropdown-block-link" ref="linksrc=search_in_mesh_link" href="https://www.ncbi.nlm.nih.gov/mesh?term=Fatty+Liver" data-ga-category="search_mesh" data-ga-action="mesh_term_link" data-ga-label="Fatty Liver / metabolism"> Search in MeSH </a></li><li><a class="add-to-search-link dropdown-block-link" ref="linksrc=add_to_search_link" role="button" data-search-term=""Fatty Liver/metabolism"[MeSH]" data-ga-category="search" data-ga-action="add_to_search" data-ga-label=""Fatty Liver/metabolism"[MeSH]" href="#"> Add to Search </a></li></ul></div></div></div></li><li><div class="keyword-actions dropdown-block"><button class="keyword-actions-trigger trigger keyword-link" aria-label="Toggle dropdown menu for keyword Fatty Liver / pathology" tabindex="0" aria-controls="keyword-actions-mesh-terms-5" aria-expanded="false" data-pinger-ignore> Fatty Liver / pathology </button><div id="keyword-actions-mesh-terms-5" 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aria-label="Toggle dropdown menu for keyword Mice" tabindex="0" aria-controls="keyword-actions-mesh-terms-7" aria-expanded="false" data-pinger-ignore> Mice </button><div id="keyword-actions-mesh-terms-7" class="keyword-actions-dropdown dropdown dropdown-container" hidden aria-label="Dropdown menu for keyword Mice"><div class="title">Actions</div><div class="content"><ul class="keyword-actions-links"><li><a class="search-in-pubmed-link dropdown-block-link" href="/?term=%22Mice%22%5BMeSH%5D&sort=date&sort_order=desc" data-href="/?term=%22Mice%22%5BMeSH%5D&sort=date&sort_order=desc" ref="linksrc=search_in_pubmed_keyword_link&mesh="Mice"[MeSH]" data-ga-category="search" data-ga-action="mesh_term" data-ga-label="Mice"> Search in PubMed </a></li><li><a class="search-in-mesh-link dropdown-block-link" ref="linksrc=search_in_mesh_link" href="https://www.ncbi.nlm.nih.gov/mesh?term=Mice" data-ga-category="search_mesh" data-ga-action="mesh_term_link" data-ga-label="Mice"> Search in MeSH 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href="/?term=%22Thyroid+Hormones%2Fmetabolism%22%5BMeSH%5D&sort=date&sort_order=desc" data-href="/?term=%22Thyroid+Hormones%2Fmetabolism%22%5BMeSH%5D&sort=date&sort_order=desc" ref="linksrc=search_in_pubmed_keyword_link&mesh="Thyroid Hormones/metabolism"[MeSH]" data-ga-category="search" data-ga-action="mesh_term" data-ga-label="Thyroid Hormones / metabolism"> Search in PubMed </a></li><li><a class="search-in-mesh-link dropdown-block-link" ref="linksrc=search_in_mesh_link" href="https://www.ncbi.nlm.nih.gov/mesh?term=Thyroid+Hormones" data-ga-category="search_mesh" data-ga-action="mesh_term_link" data-ga-label="Thyroid Hormones / metabolism"> Search in MeSH </a></li><li><a class="add-to-search-link dropdown-block-link" ref="linksrc=add_to_search_link" role="button" data-search-term=""Thyroid Hormones/metabolism"[MeSH]" data-ga-category="search" data-ga-action="add_to_search" data-ga-label=""Thyroid Hormones/metabolism"[MeSH]" href="#"> Add to Search </a></li></ul></div></div></div></li><li><div class="keyword-actions dropdown-block"><button class="keyword-actions-trigger trigger keyword-link major" aria-label="Toggle dropdown menu for keyword Triiodothyronine* / metabolism" tabindex="0" aria-controls="keyword-actions-mesh-terms-major-9" aria-expanded="false" data-pinger-ignore> Triiodothyronine* / metabolism </button><div id="keyword-actions-mesh-terms-major-9" class="keyword-actions-dropdown dropdown dropdown-container" hidden aria-label="Dropdown menu for keyword Triiodothyronine* / metabolism"><div class="title">Actions</div><div class="content"><ul class="keyword-actions-links"><li><a class="search-in-pubmed-link dropdown-block-link" href="/?term=%22Triiodothyronine%2Fmetabolism%22%5BMAJR%5D&sort=date&sort_order=desc" data-href="/?term=%22Triiodothyronine%2Fmetabolism%22%5BMAJR%5D&sort=date&sort_order=desc" ref="linksrc=search_in_pubmed_keyword_link&mesh="Triiodothyronine/metabolism"[MAJR]" data-ga-category="search" 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data-pinger-ignore> Triiodothyronine* / pharmacology </button><div id="keyword-actions-mesh-terms-major-10" class="keyword-actions-dropdown dropdown dropdown-container" hidden aria-label="Dropdown menu for keyword Triiodothyronine* / pharmacology"><div class="title">Actions</div><div class="content"><ul class="keyword-actions-links"><li><a class="search-in-pubmed-link dropdown-block-link" href="/?term=%22Triiodothyronine%2Fpharmacology%22%5BMAJR%5D&sort=date&sort_order=desc" data-href="/?term=%22Triiodothyronine%2Fpharmacology%22%5BMAJR%5D&sort=date&sort_order=desc" ref="linksrc=search_in_pubmed_keyword_link&mesh="Triiodothyronine/pharmacology"[MAJR]" data-ga-category="search" data-ga-action="mesh_term" data-ga-label="Triiodothyronine* / pharmacology"> Search in PubMed </a></li><li><a class="search-in-mesh-link dropdown-block-link" ref="linksrc=search_in_mesh_link" href="https://www.ncbi.nlm.nih.gov/mesh?term=Triiodothyronine" data-ga-category="search_mesh" 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