Neurobiology of overeating and obesity: the role of melanocortins and beyond

Abstract

The alarming increase in the incidence of obesity and obesity-associated disorders makes the etiology of obesity a widely studied topic today. As opposed to 'homeostatic feeding', where food intake is restricted to satisfy one's biological needs, the term 'non-homeostatic' feeding refers to eating for pleasure or the trend to over-consume (palatable) food. Overconsumption is considered a crucial factor in the development of obesity. Exaggerated consumption of (palatable) food, coupled to a loss of control over food intake despite awareness of its negative consequences, suggests that overeating may be a form of addiction. At a molecular level, insulin and leptin resistance are hallmarks of obesity. In this review, we specifically address the question how leptin resistance contributes to enhanced craving for (palatable) food. Since dopamine is a key player in the motivation for food, the interconnection between dopamine, leptin and neuropeptides related to feeding will be discussed. Understanding the mechanisms by which these neuropeptidergic systems hijack the homeostatic feeding mechanisms, thus leading to overeating and obesity is the primary aim of this review. The melanocortin system, one of the crucial neuropeptidergic systems modulating feeding behavior will be extensively discussed. The inter-relationship between neuronal populations in the arcuate nucleus and other areas regulating energy homeostasis (lateral hypothalamus, paraventricular nucleus, ventromedial hypothalamus etc.) and reward circuitry (the ventral tegmental area and nucleus accumbens) will be evaluated and scrutinized.