Effects of cevoglitazar, a dual PPARα/γ agonist, on ectopic fat deposition in fatty Zucker rats

摘要: AIM By acting as both insulin sensitizers and lipid-lowering agents, dual-acting peroxisome proliferator-activated receptors alpha/gamma (PPARalpha/gamma) agonists may be used to improve glucose tolerance in type 2 diabetic patients without inducing adiposity body weight gain. Here, an animal model of obesity resistance, the metabolic response cevoglitazar, a dual PPARalpha/gamma, was characterized using combination vivo ex magnetic resonance methodologies compared treatment effects fenofibrate, PPARalpha agonist, pioglitazone, PPARgamma agonist. METHODS Four groups fatty Zucker rats: (i) Vehicle; (ii) fenofibrate 150 mg/kg; (iii) pioglitazone 30 (iv) cevoglitazar 5 mg/kg were investigated before after treatment. Animals fed fat-enriched (54% kcal fat) diet for 6 weeks, weeks high fat-exposure alone followed by 4-week dosing period. RESULTS AND CONCLUSIONS Cevoglitazar effective at improving tolerance. However, unlike reduced BW gain adiposity, independent food intake. All three regimens normalized intramyocellular lipids. Metabolic profiling showed that muscle improves lipid profile via PPARalpha- PPARgamma-mediated mechanisms. Pioglitazone hepatic accumulation, while concentration below baseline levels (p < 0.05). liver, functions largely through agonism resulting increased beta-oxidation. only induced small changes composition visceral fat. In subcutaneous fat, however, similar those observed with suggesting export acids from this depot.