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Table · dataset · 2026

<p>Sequence of qPCR primers used in this study.</p>

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<div><p>Metabolic dysfunction-associated steatohepatitis (MASH) is associated with increased expression of hepatocyte peroxisome proliferator-activated receptor gamma (PPARγ, <i>Pparg</i>) and reduced expression of hepatic genes involved in the methionine cycle.

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The nuclear receptor PPARγ is activated by fatty acids, and we have shown that the knockout of <i>Pparg</i> in hepatocytes (<i>Pparg</i><sup>ΔHep</sup>) reduces the negative effects of MASH on the metabolism of methionine.

Here, we sought to determine whether hepatocyte <i>Pparg</i> 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 (<i>Pemt)</i> and cystathionine beta synthase (<i>Cbs)</i>.

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Although fasting increased hepatocyte <i>Pparg</i> expression, <i>Pparg</i><sup>ΔHep</sup> did not enhance the fasting and refeeding-mediated regulation of methionine cycle gene expression. We previously reported that diet-induced steatosis increased hepatocyte <i>Pparg</i> expression, and here we show that PPARγ-specific agonist rosiglitazone (RSG) reduced the expression of betaine homocysteine S-methyltransferase (<i>Bhmt)</i> and <i>Cbs</i> in diet-induced obese control mice.

The PPARγ-dependent reduction of hepatic <i>Bhmt</i> and <i>Cbs</i> expression was confirmed in mouse primary hepatocytes. Interestingly, <i>Pparg</i><sup>ΔHep</sup> increased the expression of <i>Pemt</i> in HFD-fed mice and that of key genes of the methionine cycle in RSG-treated obese mice, including <i>Pemt, Bhmt</i> and <i>Cbs</i>, suggesting that <i>Pparg</i> negatively regulates their expression in the liver<i>.</i></p></div>

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figshareoai:figshare.com:article/339387369 d agoJSON v1
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