Influence of topiramate in the regulation of energy balance

Topiramate (TPM) is a novel neurotherapeutic agent currently indicated for the treatment of epilepsy and undergoing development for other central nerv ous system indications including neuropathic pain, bipolar disorder, and mi graine prophylaxis. TPM is synthesized from D-fructose and contains a sulfa mate moiety that is essential for its pharmacologic activity. TPM has been observed to significantly reduce bodyweight in patients treated for seizure , which has prompted the realization of preclinical studies to characterize the effects of TPM in the regulation of energy balance. Studies carried ou t in various strains of rats have provided good evidence for the ability of TPM to blunt-energy deposition. Body composition analyses from rat trials have demonstrated that TPM inhibits fat deposition while reducing the activ ity of lipoprotein lipase (LPL)in various white adipose tissue depots. High doses of TPM (likely above the therapeutic dose range) have also been obse rved to reduce protein gain without catabolic effects. Although TPM cannot be described as a potent anorectic agent, it seems to have the ability to r educe food intake; significant reductions in food intake have been observed in female obese (fa/fa) Zucker rats and in female Wistar rats. TPM can als o reduce energy deposition in the absence of alterations in food intake. Th is effect has been clearly emphasized in female lean (Fa/?) Zucker rats. In female Sprague-Dawley rats, TPM also increased energy expenditure and it h as been observed to increase LPL activity: in brown adipose tissue, which c ould indicate that TPM has the ability to enhance regulatory thermogenesis. In addition, TPM stimulates LPL activity in skeletal muscles, further emph asizing its potential to promote substrate oxidation. The mechanisms whereb y TPM affects the regulation of energy-balance have yet to be understood. T PM represents an antiepileptic drug (AED) with complex biochemical/pharmaco logic actions. Its negative effects on energy deposition cannot be readily predicted from these actions, as AEDs are generally expected to stimulate b ody weight gain. Recent data, obtained from investigations aimed at assessi ng the effects of TPM on neuropeptidergic systems involved in the regulatio n of energy balance, have failed to demonstrate any significant effects of TPM on the neuropeptide Y and proopiomelanocortin systems. In conclusion it is clear that TPM can reduce fat deposition by either reducing food intake or stimulating energy expenditure. The mechanisms whereby an AED such as T PM controls food intake and energy expenditure remains to be delineated. Nu trition 2000;16:961-966. (C) Elsevier Science Inc. 2000.