Topiramate reduces energy and fat gains in lean (Fa/?) and obese (fa/fa) Zucker rats

Objective: This study examined the effects of topiramate (TPM), a novel neu rotherapeutic agent reported to reduce body weight in humans, on the compon ents of energy balance in female Zucker rats. Research Methods and Procedures: A 2 x 3 factorial experiment was performed in which two cohorts of Zucker rats differing in their phenotype (phenotyp e: lean, Fa/?; obese,fa/fa) were each divided into three groups defined by the dose of TPM administered (dose: TPM 0, vehicle; TPM 15, 15 mg/kg; TPM 6 0, 60 mg/kg). Results: The reduction in body weight gain induced by TPM in both lean and obese rats reflected a decrease in total body energy gain, which was more e vident in obese than in lean rats. Whereas TPM administration did not influ ence the intake of digestible energy in lean rats, it induced a reduction i n food intake in obese animals. In lean, but not in obese rats, apparent en ergy expenditure las calculated by the difference between energy intake and energy gain) was higher in rats treated with TPM than in animals administe red the vehicle. The low dose of TPM decreased fat gain (with emphasis on s ubcutaneous fat) without affecting protein gain, whereas the high dose of t he drug induced a reduction in both fat and protein gains. The effects of T PM on muscle and fat depot weights were representative of the global effect s of TPM on whole body fat and protein gains. The calculated energetic effi ciency (energy gain/energy intake) was decreased in both lean and obese rat s after TPM treatment. TPM dose independently reduced hyperinsulinemia of o bese rats, but it did not alter insulinemia of lean animals. Discussion: The present results provide sound evidence for the ability of T PM to reduce fat and energy gains through reducing energetic efficiency in both lean and obese Zucker rats.