On the Role of Neuropeptides in the Hypothalamic Regulation of Food Intake

Neuropeptides are molecules of outstanding importance in the regulation of most different physiological and biochemical processes. They act as signal transducting molecules that makes them an ideal target for pharmacological treatment. Because of their possibility to act via different receptor subtypes within a whole receptor family, the peptides are able to selectively induce physiological processes. Therefore, peptide research provides important contributions to a detailed understanding of physiological processes. The hypothalamic regulation of food intake reveals a redundant system of neuropeptides, acting and interacting with each other in order to control energy homeostasis and body weight. Leptin and insulin are peripheral adiposity signals, inducing first order neuronal signalling in the arcuate nucleus of the hypothalamus. There, they inhibit anabolic peptides, whereas they stimulate catabolic peptides. Neurons from the arcuate nucleus project to candidate second-order neurons involved in hypothalamic response to leptin and insulin, located in the paraventricular nucleus and the lateral hypothalamic and perifornical area. However, anomalies in body weight, especially overweight and obesity, are not only genetically determined, but also by the environment. Cultural, socioeconomic and psychosocial factors, physical activity and other environmental factors are known for sustained influence of body weight. Medicinal chemistry importantly contributes to the molecular understanding of anomalies and diseases, which likely culminates in the development of appropriate medical treatments. Hereby, the development of receptor subtype selective agonists and antagonists is a key step. This is exemplified on a set of hypothalamic neuropeptides which are involved in the regulation of food intake.