Fenofibrate ameliorates diabetic and dyslipidemic profiles in KKAy mice partly via down-regulation of 11beta-HSD1, PEPCK and DGAT2. Comparison of PPARalpha, PPARgamma, and liver x receptor agonists.

摘要: Abstract Fenofibrate and rosiglitazone are prescribed to treat hypertriglyceridemia diabetes, respectively. Since fenofibrate improves lipid profile in diabetic patients insulin resistance animal models, we examined the mechanism of antidiabetic effects KKAy mouse, an model diabetes dyslipidemia. mice were treated with fenofibrate, rosiglitazone, liver x receptor agonist, N-(2,2,2-trifluoroethyl)-N-[4-[2,2,2-trifluoro-1-hydroxy-1-(trifluoromethyl)ethyl]phenyl]-benzenesulfonamide (T0901317), a combination T090317 for 2 weeks. lowered serum triglycerides by 90% free fatty acid (FFA) 50% via inhibition hepatic synthesis. also prevented T0901317-induced increases dampening T090317-mediated sterol response element binding protein 1c (SREBP1c) up-regulation. Glucose lowering was comparable (~ 40%) mice. showed mild reduction glucose, part, down-regulation phosphoenol pyruvate carboxykinase (PEPCK). Combining T0901317 caused greater suggesting additive effect. The glucose examined. Liver PEPCK all treatment groups showing effects. Combination on down-regulation. decreased diacyl glycerol acyl transferase 2 (DGAT2) mRNA leading triglyceride Most importantly, down regulated expression adipose 11beta hydroxysteroid dehydrogenase (11β-HSD1) gene, which contributed attenuating state. Thus, amelioration hyperlipidemic state occurred DGAT2, 11β-HSD1. It is shown that undesirable lipogenic could be dampened fenofibrate.