{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T03:06:16Z","timestamp":1791515176991,"version":"4.3.4"},"reference-count":70,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2022,10,15]],"date-time":"2022-10-15T00:00:00Z","timestamp":1665792000000},"content-version":"vor","delay-in-days":287,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81770582"],"award-info":[{"award-number":["81770582"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Oxidative Medicine and Cellular Longevity"],"published-print":{"date-parts":[[2022,1]]},"abstract":"<jats:p>\n                    Nonalcoholic steatohepatitis (NASH) is a chronic and progressive disease whose treatment strategies are limited. Although time\u2010restricted feeding (TRF) is beneficial for metabolic diseases without influencing caloric intake, the underlying mechanisms of TRF action in NASH and its efficacy have not yet been demonstrated. We herein showed that TRF effectively alleviated NASH, producing a reduction in liver enzymes and improvements in liver pathology. Regarding the mechanisms by which TRF mitigates NASH, we ascertained that TRF inhibited ferroptosis and the expression of the circadian gene Per2. By adopting a hepatocyte\u2010specific Per2\u2010knockout (Per2\n                    <jats:sup>\u25b3hep<\/jats:sup>\n                    ) mice model, we clarified the critical role of Per2 in exacerbating NASH. According to the results of our RNA\u2010Seq analysis, the knockout of Per2 ameliorated NASH by inhibiting the onset of ferroptosis; this was manifested by diminished lipid peroxidation levels, decreased mRNA and protein levels for ferroptosis\u2010related genes, and alleviated morphologic changes in mitochondria. Furthermore, using a ferroptosis inhibitor, we showed that ferroptosis significantly aggravated NASH and noted that this was likely achieved by regulation of the expression of peroxisome proliferator activated receptor (PPAR)\n                    <jats:italic>\u03b1<\/jats:italic>\n                    . Finally, we discerned that TRF and hepatocyte\u2010specific knockout of Per2 promoted the expression of PPAR\n                    <jats:italic>\u03b1<\/jats:italic>\n                    . Our results revealed a potential for TRF to effectively alleviate high\u2010fat and high\u2010fructose diet\u2010induced NASH via the inhibition of Per2 and depicted the participation of Per2 in the progression of NASH by promoting ferroptosis, which was ultimately related to the expression of PPAR\n                    <jats:italic>\u03b1<\/jats:italic>\n                    .\n                  <\/jats:p>","DOI":"10.1155\/2022\/8063897","type":"journal-article","created":{"date-parts":[[2022,10,15]],"date-time":"2022-10-15T18:20:05Z","timestamp":1665858005000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":25,"title":["Attenuation by Time\u2010Restricted Feeding of High\u2010Fat and High\u2010Fructose Diet\u2010Induced NASH in Mice Is Related to Per2 and 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