{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T16:17:19Z","timestamp":1785428239178,"version":"3.56.0"},"reference-count":42,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2026,4,6]],"date-time":"2026-04-06T00:00:00Z","timestamp":1775433600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100011611","name":"Shinshu Public Utility Foundation for Promotion of Medical Sciences","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100011611","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100009619","name":"Japan Agency for Medical Research and Development","doi-asserted-by":"crossref","award":["JP23fk0210125"],"award-info":[{"award-number":["JP23fk0210125"]}],"id":[{"id":"10.13039\/100009619","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100009619","name":"Japan Agency for Medical Research and Development","doi-asserted-by":"crossref","award":["JP256f0137007"],"award-info":[{"award-number":["JP256f0137007"]}],"id":[{"id":"10.13039\/100009619","id-type":"DOI","asserted-by":"crossref"}]},{"award":["JP23fk0210125"],"award-info":[{"award-number":["JP23fk0210125"]}],"id":[{"id":"https:\/\/ror.org\/004rtk039","id-type":"ROR","asserted-by":"publisher"}]},{"award":["JP256f0137007"],"award-info":[{"award-number":["JP256f0137007"]}],"id":[{"id":"https:\/\/ror.org\/004rtk039","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>We previously demonstrated that a clinically relevant dose of pemafibrate (PEM), a selective peroxisome proliferator-activated receptor \u03b1 (PPAR\u03b1) modulator (SPPARM\u03b1), reduces serum triglyceride (TG) levels in mice via hepatic PPAR\u03b1 activation. However, the specific contribution of hepatocyte PPAR\u03b1 remains unclear. To address this, male Ppara-floxed (Pparafl\/fl) and hepatocyte-specific Ppara-disrupted (Ppara\u0394Hep) mice were fed a diet with or without a clinically relevant dose of PEM (0.00005%) for four weeks. In Pparafl\/fl mice, PEM significantly reduced circulating TG and non-esterified fatty acid levels by enhancing hepatic fatty acid uptake and \u03b2-oxidation. In contrast, these effects were absent in Ppara\u0394Hep mice. Notably, PEM did not activate PPAR\u03b1 in extrahepatic tissues, including white\/brown adipose tissue, kidney, and skeletal muscle in either genotype. These findings underscore the essential role of hepatocyte PPAR\u03b1 in mediating the pharmacological effects of PEM at clinically relevant doses.<\/jats:p>","DOI":"10.3390\/ijms27073308","type":"journal-article","created":{"date-parts":[[2026,4,7]],"date-time":"2026-04-07T08:09:00Z","timestamp":1775549340000},"page":"3308","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Hepatocyte PPAR\u03b1 Is Essential for Triglyceride-Lowering Effect of Pemafibrate"],"prefix":"10.3390","volume":"27","author":[{"given":"Zhe","family":"Zhang","sequence":"first","affiliation":[{"name":"Department of Global Medical Research Promotion, Shinshu University Graduate School of Medicine, Matsumoto 390-8621, Japan"},{"name":"Gastroenterology Department, University-Town Hospital of Chongqing Medical University, The Fourth Clinical College of Chongqing Medical University, Chongqing 401331, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuguang","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Global Medical Research Promotion, Shinshu University Graduate School of Medicine, Matsumoto 390-8621, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chufang","family":"Qian","sequence":"additional","affiliation":[{"name":"Department of Global Medical Research Promotion, Shinshu University Graduate School of Medicine, Matsumoto 390-8621, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pan","family":"Diao","sequence":"additional","affiliation":[{"name":"Department of Global Medical Research Promotion, Shinshu University Graduate School of Medicine, Matsumoto 390-8621, Japan"},{"name":"Department of Clinical Laboratory, The Second Hospital of Hebei Medical University, Shijiazhuang 050061, China"},{"name":"Postdoctoral Mobile Station of Clinical Medicine, Hebei Medical University, Shijiazhuang 050017, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2678-788X","authenticated-orcid":false,"given":"Takero","family":"Nakajima","sequence":"additional","affiliation":[{"name":"Department of Global Medical Research Promotion, Shinshu University Graduate School of Medicine, Matsumoto 390-8621, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1481-1029","authenticated-orcid":false,"given":"Takefumi","family":"Kimura","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, Shinshu University School of Medicine, Matsumoto 390-8621, Japan"},{"name":"Institute for Biomedical Sciences, Shinshu University, Matsumoto 390-8621, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frank J.","family":"Gonzalez","sequence":"additional","affiliation":[{"name":"Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3212-3836","authenticated-orcid":false,"given":"Naoki","family":"Tanaka","sequence":"additional","affiliation":[{"name":"Department of Global Medical Research Promotion, Shinshu University Graduate School of Medicine, Matsumoto 390-8621, Japan"},{"name":"Institute for Biomedical Sciences, Shinshu University, Matsumoto 390-8621, Japan"},{"name":"International Relations Office, Shinshu University School of Medicine, Matsumoto 390-8621, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,4,6]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1002\/j.2040-4603.2014.tb00548.x","article-title":"Energy metabolism in the liver","volume":"4","author":"Rui","year":"2014","journal-title":"Compr. 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