Fenofibrate prevents and reduces body weight gain and adiposity in diet-induced obese rats

Fibrates are hypolipidemic drugs that activate the peroxisome proliferator- activated receptors, Since fibrates may also increase energy expenditure, m e investigated whether fenofibrate (FF) had this effect in diet-induced obe se rats. A 2-month administration of a high-fat palatable diet to adult rat s increased body weight by 25% and white adipose mass by 163% compared with a standard diet. These effects mere prevented by FF, both when administere d for the 2 months of high-fat feeding and when given for only the second m onth. Consequently, FF-treated rats had a final body weight and white adipo se tissue mass similar to untreated animals on the standard diet. FF also i ncreased resting metabolic rate, hepatic peroxisomal and mitochondrial palm itoyl-dependent oxygen uptake and mRNA levels of acyl-CoA oxidase and lipop rotein lipase, Finally, FF lowered mRNA levels of uncoupling protein-2 and did not affect mitochondrial respiration in skeletal muscle. Therefore, FF seems to act as a weight-stabilizer mainly through its effect on liver meta bolism (C) 2001 Federation of European Biochemical Societies. Published by Elsevier Science B.V. All rights reserved.