Sibutramine effects on central mechanisms regulating energy homeostasis

Abstract

During the last 50 years the global pandemic of obesity and associated life-threatening co-morbidities strongly promoted the development of anti-obesity pharmacotherapy. Sibutramine is an anti-obesity drug that in conjunction with lifestyle modifications reduces food intake and body weight. This may result from several effects: inhibition of presynaptic reuptake of monoaminergic neurotransmitters in the central nervous system, thereby suppressing appetite, induction of an increase in anorexigenic and a decrease in orexigenic neuropeptide secretion, induction of an increase in energy expenditure, and induction of peripheral sympathomimetic effects. The effects of sibutramine on anabolic and catabolic signals that regulate energy homeostasis in the hypothalamus are not completely understood. So, the aim of this review is to summarize the central mechanisms of action of sibutramine, responsible for its weight and food intake reducing potential. Despite being a useful drug in obesity treatment, awareness about the loss of long-term effectiveness and detrimental side effects of sibutramine has recently emerged. As a consequence, new drugs that produce safer and more persistent weight loss are currently undergoing clinical trials.

Keywords: Appetite; hypothalamus; obesity; sibutramine; weight loss..

Fig. (1)

Neuroanatomical model summarizing the different pathways that control energy homeostasis. During meals, episodic and tonic signals, such as the satiety signals cholecystokinin (CCK) and the adiposity signals leptin and insulin, are conveyed through the vagus nerve to the arcuate nucleus (ARC) and nucleus of the solitary tract (NTS). These signals interact with neurons that synthesize anorexigenic and orexigenic neuropeptides, like proopiomelanocorticotropin (POMC)/cocaine amphetamine regulating transcript (CART) or neuropeptide Y (NPY)/agouti related peptide (AgRP), respectively, which in turn project to other hypothalamic areas including the paraventricular nuclei (PVN) and the lateral hypothalamic area (LHA). Figure reproduced, with permission, from Reference [5]. Abbreviations: GI, gastrointestinal; PFA, perifornical area; SNS, sympathetic nervous system.