title: Dietary component isorhamnetin is a PPARγ antagonist and ameliorates metabolic disorders induced by diet or leptin deficiency.
abstract: Studies on peroxisome proliferator-activated receptor (PPAR)-γ ligands have been focused on agonists. However, PPARγ activation may induce obesity and nonalcoholic fatty liver disease (NAFLD), one of the most challenging medical conditions. Here, we identified that isorhamnetin, a naturally occurring compound in fruits and vegetables and the metabolite of quercetin, is a novel antagonist of PPARγ. Isorhamnetin treatment inhibited the adipocyte differentiation induced by the PPARγ agonist rosiglitazone, reduced obesity development and ameliorated hepatic steatosis induced by both high-fat diet treatment and leptin deficiency. Our results suggest that dietary supplement of isorhamnetin may be beneficial to prevent obesity and steatosis and PPARγ antagonists may be useful to treat hepatic steatosis.
authors.affiliation: School of Pharmacy, Shanghai University of Traditional Chinese Medicine, 1200 Cailun Road, Shanghai 201203, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: School of Pharmacy, Shanghai University of Traditional Chinese Medicine, 1200 Cailun Road, Shanghai 201203, China.
authors.forename: Ming
authors.initials: M
authors.lastname: Gu
authors.affiliation: School of Pharmacy, Shanghai University of Traditional Chinese Medicine, 1200 Cailun Road, Shanghai 201203, China.
authors.forename: Wujie
authors.initials: W
authors.lastname: Cai
authors.affiliation: School of Pharmacy, Shanghai University of Traditional Chinese Medicine, 1200 Cailun Road, Shanghai 201203, China.
authors.forename: Lijing
authors.initials: L
authors.lastname: Yu
authors.affiliation: School of Pharmacy, Shanghai University of Traditional Chinese Medicine, 1200 Cailun Road, Shanghai 201203, China.
authors.forename: Li
authors.initials: L
authors.lastname: Feng
authors.affiliation: School of Pharmacy, Shanghai University of Traditional Chinese Medicine, 1200 Cailun Road, Shanghai 201203, China.
authors.forename: Lu
authors.initials: L
authors.lastname: Zhang
authors.affiliation: School of Pharmacy, Shanghai University of Traditional Chinese Medicine, 1200 Cailun Road, Shanghai 201203, China.
authors.forename: Qingqing
authors.initials: Q
authors.lastname: Zang
authors.affiliation: School of Pharmacy, Shanghai University of Traditional Chinese Medicine, 1200 Cailun Road, Shanghai 201203, China.
authors.forename: Yahui
authors.initials: Y
authors.lastname: Wang
authors.affiliation: School of Pharmacy, Shanghai University of Traditional Chinese Medicine, 1200 Cailun Road, Shanghai 201203, China.
authors.forename: Dongshan
authors.initials: D
authors.lastname: Wang
authors.affiliation: School of Pharmacy, Shanghai University of Traditional Chinese Medicine, 1200 Cailun Road, Shanghai 201203, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Chen
authors.affiliation: Brown Foundation Institute of Molecular Medicine and Programs in Neuroscience and Biochemistry, University of Texas Medical School at Houston, TX 77030, USA.
authors.forename: Qingchun
authors.initials: Q
authors.lastname: Tong
authors.affiliation: Institute of Digestive Disease, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China.
authors.forename: Guang
authors.initials: G
authors.lastname: Ji
authors.affiliation: School of Pharmacy, Shanghai University of Traditional Chinese Medicine, 1200 Cailun Road, Shanghai 201203, China.
authors.forename: Cheng
authors.initials: C
authors.lastname: Huang
mesh_terms: D041721:3T3-L1 Cells; D017667:Adipocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D050156:Adipogenesis / Q000187:drug effects / Q000235:genetics; D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects; D059305:Diet, High-Fat / Q000009:adverse effects*; D019587:Dietary Supplements; D004195:Disease Models, Animal; D005786:Gene Expression Regulation; D006801:Humans; D020738:Leptin / Q000172:deficiency*; D008659:Metabolic Diseases / Q000209:etiology* / Q000378:metabolism*; D051379:Mice; D008958:Models, Molecular; D008968:Molecular Conformation; D065626:Non-alcoholic Fatty Liver Disease / Q000209:etiology / Q000378:metabolism; D009765:Obesity / Q000209:etiology / Q000378:metabolism; D047495:PPAR gamma / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000378:metabolism; D011485:Protein Binding; D011794:Quercetin / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology; D015533:Transcriptional Activation
chemical_list: D020738:Leptin; D047495:PPAR gamma; C047368:3-methylquercetin; D011794:Quercetin