title: Kaempferol regulates the lipid-profile in high-fat diet-fed rats through an increase in hepatic PPARα levels.
abstract: The aim of this study was to investigate the antiobesity and antihyperlipidemic effects of the flavonoid kaempferol (3,5,7,4'-tetrahydroxyflavone). After being fed a high-fat diet (HFD) for two weeks, rats were dosed orally with kaempferol (75, 150, or 300 mg/kg) or fenofibrate (100 mg/kg) once daily for eight weeks. Fenofibrate is an antilipemic agent that exerts its therapeutic effects through activation of peroxisome proliferator-activated receptor α (PPAR α). Kaempferol (300 mg/kg/day) produced effects similar to fenofibrate in reducing body weight gain, visceral fat-pad weights, plasma lipid levels, as well as the coronary artery risk and atherogenic indices of HFD-fed rats. Kaempferol also caused dose-related reductions in hepatic triglyceride and cholesterol content and lowered hepatic lipid droplet accumulation and the size of epididymal adipocytes in HFD-fed rats. Kaempferol and fenofibrate reversed the HFD-induced downregulation of hepatic PPAR α. HFD-induced reductions in the hepatic levels of acyl-CoA oxidase (ACO), and cytochrome P450 isoform 4A1 (CYP4A1) proteins were reversed by kaempferol and fenofibrate. The elevated expression of hepatic sterol regulatory element binding proteins (SREBPs) in HFD-fed rats were lowered by kaempferol and fenofibrate. These results suggest that kaempferol reduced the accumulation of visceral fat and improved hyperlipidemia in HFD-fed obese rats by increasing lipid metabolism through the downregulation of SREBPs and promoting the hepatic expression of ACO and CYP4A1, secondary to a direct upregulation hepatic PPAR α expression.
authors: School of Chinese Pharmaceutical Sciences and Chinese Medicine Resources, China Medical University, Taichung, Taiwan.
authors: Chia Ju
authors: CJ
authors: Chang
authors: Thing-Fong
authors: TF
authors: Tzeng
authors: Shorong-Shii
authors: SS
authors: Liou
authors: Yuan-Shiun
authors: YS
authors: Chang
authors: I-Min
authors: IM
authors: Liu
mesh_terms: D042962:Acyl-CoA Oxidase / Q000378:metabolism; D017667:Adipocytes / Q000187:drug effects / Q000378:metabolism; D000284:Administration, Oral; D000818:Animals; D042926:Cytochrome P-450 CYP4A / Q000378:metabolism; D059305:Diet, High-Fat / Q000009:adverse effects; D004305:Dose-Response Relationship, Drug; D011345:Fenofibrate / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects*; D000960:Hypolipidemic Agents / Q000494:pharmacology*; D044949:Kaempferols / Q000494:pharmacology*; D050356:Lipid Metabolism / Q000187:drug effects; D008055:Lipids / Q000097:blood; D008099:Liver / Q000201:enzymology / Q000503:physiopathology*; D008297:Male; D047493:PPAR alpha / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D051779:Sterol Regulatory Element Binding Proteins / Q000378:metabolism; D015430:Weight Gain / Q000187:drug effects
chemical_list: D000960:Hypolipidemic Agents; D044949:Kaempferols; D008055:Lipids; D047493:PPAR alpha; D051779:Sterol Regulatory Element Binding Proteins; C006552:kaempferol; D042926:Cytochrome P-450 CYP4A; D042962:Acyl-CoA Oxidase; D011345:Fenofibrate