KO's and organisation of peptidergic feeding behavior mechanisms

Feeding behavior results from complex interactions arising between numerous neuromediators, including classical neurotransmitters and neuropeptides pr esent in hypothalamic networks. One way to unravel these complex mechanisms is to examine animal models with a deletion of genes coding for the differ ent neuropeptides involved in the regulation of feeding. The aim of this re view is to focus on feeding and body weight regulation in mice lacking neur opeptide Y (NPY), melanocortins (POMC), corticotropin-releasing hormone, me lanin-concentrating hormone, or bombesin-like peptides respectively. The ph enotypes, which relate to the deletion of gene coding for the peptides, rar ely include changes in body weight and food intake, indicating therefore th e existence of redundant mechanisms to compensate for the loss of the pepti de. The phenotype is much more marked when the gene deletion is targeted to wards the functioning of the peptidergic machinery, e.g. the receptors and especially the POMC and NPY receptors, as well as one subtype of bombesin r eceptor (BRS-3). These knockout models are also interesting when examining the role of environmental and social factors in the determination of feedin g behavior. They have granted us better knowledge of all these integrated a nd complex mechanisms. Moreover, they are also valuable tools for pharmacol ogical studies when specific antagonists are lacking. From the information obtained by the study of knockouts, it is possible to determine certain tar gets for selective drugs that could be efficient for the pharmacological tr eatment of obesity. However, at the present state of our knowledge, it seem s necessary to target several peptides in order to get good results with we ight loss. It will also be imperative to associate these multitherapies wit h changes in eating and behavioral habits, in order to obtain complete effe ctiveness and long-lasting results. (C) 2001 Elsevier Science Ltd. All righ ts reserved.