HYPOTHALAMIC PROOPIOMELANOCORTIN MESSENGER-RNA IS REDUCED BY FASTING IN OB OB AND DB/DB MICE, BUT IS STIMULATED BY LEPTIN/

Reduction in the activity of the alpha-melanocyte-stimulating hormone (alpha-MSH) system causes obesity and infusions of alpha-MSH call prod uce satiety, raising the possibility that alpha-MSH may mediate physio logical satiety signals, Since alpha-MSH is coded for by the pro-opiom elanocortin (POMC) gene, pie examined if POMC gene expression would be inhibited by fasting in normal mice or in models of obesity character ized by leptin insufficiency (ob/ob) or leptin insensitivity (db/db). in wild-type mice, hypothalamic POMC mRNA was decreased >60% after a 2 -day fast and was positively correlated with leptin mRNA. Similarly co mpared with controls, POMC mRNA was decreased by at least 60% in both db/db and ob/ob mice, POMC mRNA was negatively correlated with both ne uropeptide Y (NPY) and melanin-concentrating hormone (MCH) mRNA, Final ly, treatment of both male and female ob/ob mice with leptin stimulate d hypothalamic POCM mRNA by about threefold, These results suggest tha t impairment in production, processing, or responsiveness to alpha-MSH may be a common feature of obesity and that hypothalamic POMC neurons , stimulated by leptin, may constitute a Link between leptin and the m elanocortin system.