Effect of topiramate on body weight and body composition of Osborne-Mendelrats fed a high-fat diet: Alterations in hormones, neuropeptide, and uncoupling protein mRNAs

The effects of topiramate on food intake and body composition were investig ated in rats fed a high-fat diet and compared with rats that were pair fed or treated with D-fenfluramine. Topiramate (40 mg.kg.d for 80 d) reduced bo dy-weight gain in a manner similar to that of pair-fed rats and D-fenfluram ine-treated rats. The reduction in body fat accounted for all the weight re duction after topiramate treatment but not after pair feeding or D-fenflura mine treatment. Topiramate reduced food intake acutely and increased metabo lic rate. There were also significant reductions in leptin, insulin, and co rticosterone. In the hypothalamus, topiramate increased mRNA for neuropepti de Y, reduced mRNA for neuropeptide-Y Y1 and Y5 receptors, corticotropin-re leasing hormone (CRH), and;type II glucocorticoid receptors but had no effe ct on mRNA levels for the short or long form of the leptin receptor. In per ipheral tissues, topiramate reduced leptin mRNA in adipose tissue, had no e ffect on uncoupling protein 1 mRNA in brown adipose tissue but had tissue-s elective effects on uncoupling proteins 2 and 3 mRNA levels in white and br own adipose tissues and muscle. In conclusion, topiramate is an effective i nhibitor of weight gain in rats on a high-fat diet, but the mechanism throu gh which the change in energy balance is achieved is unclear. Nutrition 200 0;16:967-975. (C) Elsevier Science Inc. 2000.