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The nuclear receptor PPAR\u03b3 is activated by fatty acids, and we have shown that the knockout of\n                    <jats:italic>Pparg<\/jats:italic>\n                    in hepatocytes (\n                    <jats:italic>Pparg<\/jats:italic>\n                    <jats:sup>\u0394Hep<\/jats:sup>\n                    ) reduces the negative effects of MASH on the metabolism of methionine. Here, we sought to determine whether hepatocyte\n                    <jats:italic>Pparg<\/jats:italic>\n                    is required for the transcriptional regulation of genes involved in the methionine cycle in conditions with altered fatty acid flux to the liver: fasting, refeeding, and high-fat diet (HFD)-induced obesity\/steatosis. Fasting increased the expression of key genes involved in the methionine cycle, whereas 6h-refeeding reversed these effects and reduced the expression of phosphatidylethanolamine N-methyltransferase (\n                    <jats:italic>Pemt)<\/jats:italic>\n                    and cystathionine beta synthase (\n                    <jats:italic>Cbs)<\/jats:italic>\n                    . Although fasting increased hepatocyte\n                    <jats:italic>Pparg<\/jats:italic>\n                    expression,\n                    <jats:italic>Pparg<\/jats:italic>\n                    <jats:sup>\u0394Hep<\/jats:sup>\n                    did not enhance the fasting and refeeding-mediated regulation of methionine cycle gene expression. We previously reported that diet-induced steatosis increased hepatocyte\n                    <jats:italic>Pparg<\/jats:italic>\n                    expression, and here we show that PPAR\u03b3-specific agonist rosiglitazone (RSG) reduced the expression of betaine homocysteine S-methyltransferase (\n                    <jats:italic>Bhmt)<\/jats:italic>\n                    and\n                    <jats:italic>Cbs<\/jats:italic>\n                    in diet-induced obese control mice. The PPAR\u03b3-dependent reduction of hepatic\n                    <jats:italic>Bhmt<\/jats:italic>\n                    and\n                    <jats:italic>Cbs<\/jats:italic>\n                    expression was confirmed in mouse primary hepatocytes. Interestingly,\n                    <jats:italic>Pparg<\/jats:italic>\n                    <jats:sup>\u0394Hep<\/jats:sup>\n                    increased the expression of\n                    <jats:italic>Pemt<\/jats:italic>\n                    in HFD-fed mice and that of key genes of the methionine cycle in RSG-treated obese mice, including\n                    <jats:italic>Pemt, Bhmt<\/jats:italic>\n                    and\n                    <jats:italic>Cbs<\/jats:italic>\n                    , suggesting that\n                    <jats:italic>Pparg<\/jats:italic>\n                    negatively regulates their expression in the liver\n                    <jats:italic>.<\/jats:italic>\n                  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America"],"department":["Department of Medicine, Division of Endocrinology, Diabetes and Metabolism"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rhonda D.","family":"Kineman","sequence":"additional","affiliation":[{"name":"University of Illinois Chicago","place":["Chicago, Illinois, United States of America"],"department":["Department of Medicine, Division of Endocrinology, Diabetes and Metabolism"]},{"name":"Jesse Brown VA Medical Center","place":["Chicago, Illinois, United States of America"],"department":["Research and Development Division"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8787-2706","authenticated-orcid":true,"given":"Jose","family":"Cordoba-Chacon","sequence":"additional","affiliation":[{"name":"University of Illinois Chicago","place":["Chicago, Illinois, United States of America"],"department":["Department of Medicine, Division of Endocrinology, Diabetes and 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