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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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3T3-L1 Cells
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Adipocytes / cytology
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Adipocytes / drug effects
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Adipocytes / metabolism
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Adipogenesis / drug effects
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Adipogenesis / genetics
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Animals
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Cell Differentiation / drug effects
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Diet, High-Fat / adverse effects*
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Dietary Supplements*
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Disease Models, Animal
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Gene Expression Regulation
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Humans
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Leptin / deficiency*
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Metabolic Diseases / etiology*
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Metabolic Diseases / metabolism*
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Mice
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Models, Molecular
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Molecular Conformation
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Non-alcoholic Fatty Liver Disease / etiology
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Non-alcoholic Fatty Liver Disease / metabolism
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Obesity / etiology
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Obesity / metabolism
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PPAR gamma / antagonists & inhibitors*
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PPAR gamma / chemistry
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PPAR gamma / metabolism
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Protein Binding
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Quercetin / analogs & derivatives*
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Quercetin / chemistry
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Quercetin / pharmacology
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Transcriptional Activation
Substances
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Leptin
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PPAR gamma
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3-methylquercetin
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Quercetin