A ROLE FOR MELANIN-CONCENTRATING HORMONE IN THE CENTRAL REGULATION OFFEEDING-BEHAVIOR

THE hypothalamus plays a central role in the integrated regulation of energy homeostasis and body weight, and a number of hypothalamic neuro peptides, such as neuropeptide Y (ref. 1), galanin(2), CRH (ref. 3), a nd GLP-1 (ref. 4), have been implicated in the mediation of these effe cts. To discover new hypothalamic peptides involved in the regulation of body weight, we used differential display polymerase chain reaction (5) to identify messenger RNAs that are differentially expressed in th e hypothalamus of ob/+ compared with ob/ob C57Bl/6J mice. We show here that one mRNA that is overexpressed in the hypothalamus of ob/ob mice encodes the neuropeptide melanin-concentrating hormone (MCH). Fasting further increased expression of MCH mRNA in both normal and obese ani mals. Neurons containing MCH are located in the zona incerta and in th e lateral hypothalamus. These areas are involved in regulation of inge stive behaviour, but the role of MCH in mammalian physiology is unknow n. To determine whether MCH is involved in the regulation of feeding, we injected MCH into the lateral ventricles of rats and found that the ir food consumption increased. These findings suggest that MCH partici pates in the hypothalamic regulation of body weight.