Potential Role of Neuropeptide Ligands in the Treatment of Overeating

Summary This article reviews the role of various neuropeptides in controlling eating behaviour and the prospects for ligands of these signalling systems in the treatment of eating disorders, in particular overeating and obesity. Neuropeptide Y is the most well known appetite-stimulating peptide. It is believed to exert this action through either Y 1 or Y 5 receptor subtypes in the hypothalamus. Selected antagonists with high affinity for these subtypes reduce food intake in animals, and so suggest that the development of clinically useful analogues may be possible. Galanin, another appetite-stimulating peptide, has been less well studied and the development of antagonists for galanin receptors is less well advanced. Studies using combinations of neuropeptide Y and galanin receptor antagonists, that may target carbohydrate and fat intake, respectively, have not yet been reported. Several peptides are known to inhibit food intake. Agonists of receptors for these peptides that have a long duration of action could be useful appetite suppressants. These peptides include ‘gut’ peptides such as cholecystokinin and glucagon-like peptide, and ‘pancreatic’ peptides such as amylin and insulin. Recently, the obesity (ob/ob) gene—related peptide leptin has been proposed as an endogenous signalling system that regulates fat intake, and a novel analogue of leptin has been shown to reduce food intake in rats. These peptides are thought to act on feeding-related regions at various levels of the neuraxis, prominently including the nucleus of the solitary tract, the lateral parabrachial nucleus, the paraventricular hypothalamus and the amygdala.