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Herein, we investigated the inhibitory effects and underlying governing mechanism of clitorin in a western diet (WD)-induced hepatic steatosis mouse model, and in oleic acid-stimulated HepG2 cells. Male C57BL\/6 mice were fed a normal diet, WD, WD\u2009+\u200910 or 20\u00a0mg\/kg orlistat, and WD\u2009+\u200910 or 20\u00a0mg\/kg clitorin. HepG2 cells were treated with 1\u00a0mM oleic acid to induce lipid accumulation with or without clitorin. Clitorin significantly alleviated body weight gain and hepatic steatosis features (NAFLD activity score, micro-, and macro-vesicular steatosis) in WD-induced hepatic steatosis mice. Additionally, clitorin significantly decreased protein expressions of sterol regulatory element-binding protein 1 (SREBP1), peroxisome proliferator-activated receptor \u03b3 (PPAR\u03b3), and CCAAT\/enhancer binding protein \u03b1 (C\/EBP\u03b1) in WD-induced hepatic steatosis mice. Moreover, clitorin significantly diminished the mRNA levels of <jats:italic>SREBP1<\/jats:italic>, acetyl-CoA carboxylase (<jats:italic>ACC<\/jats:italic>), fatty acid synthase (<jats:italic>FAS<\/jats:italic>), and hydroxy-3-methylglutaryl coenzyme A reductase (<jats:italic>HMGCR<\/jats:italic>) and enhanced the mRNA levels of peroxisome proliferator-activated receptor \u03b1 (<jats:italic>PPAR\u03b1<\/jats:italic>) and carnitine palmitoyltranserase-1 (<jats:italic>CTP-1<\/jats:italic>), as well as adenosine monophosphate-activated protein kinase (<jats:italic>AMPK<\/jats:italic>) in the liver of WD-induced hepatic steatosis mice and oleic acid-stimulated HepG2 cells. Overall, our findings demonstrated that clitorin can be a potentially efficacious candidate for NAFLD management.<\/jats:p>","DOI":"10.1038\/s41598-022-07937-3","type":"journal-article","created":{"date-parts":[[2022,3,9]],"date-time":"2022-03-09T11:02:36Z","timestamp":1646823756000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Clitorin ameliorates western diet-induced hepatic steatosis by regulating lipogenesis and fatty acid oxidation in vivo and in vitro"],"prefix":"10.1038","volume":"12","author":[{"given":"Divina C.","family":"Cominguez","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yea-Jin","family":"Park","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yun-Mi","family":"Kang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Agung","family":"Nugroho","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Suhyun","family":"Kim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hyo-Jin","family":"An","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2022,3,9]]},"reference":[{"key":"7937_CR1","doi-asserted-by":"publisher","first-page":"845","DOI":"10.3390\/cells8080845","volume":"8","author":"HK Drescher","year":"2019","unstructured":"Drescher, H. 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