The catabolic action of insulin in the brain is mediated by melanocortins.
Like leptin, the pancreatic hormone insulin is an important adiposity signal to the brain. We report that the hypothalamic melanocortin system is an important target of the actions of insulin to regulate food intake and body weight. Hypothalamic neurons expressing insulin receptors were found to coexpress the melanocortin precursor molecule pro-opiomelanocortin (POMC), and administration of insulin into the third cerebral ventricle of fasted rats increased expression of POMC mRNA. Finally, a subthreshold dose of the melanocortin antagonist SHU-9119 prevented the reduction in food intake caused by third-ventricular insulin administration. These data suggest that the hypothalamic melanocortin system mediates the anorexic effects of central insulin, as well as of leptin.
Benoit
Stephen C
SC
Department of Psychiatry, University of Cincinnati, College of Medicine, Cincinnati, Ohio 45267-0559, USA. stephen.benoit@uc.edu
Air
Ellen L
EL
Coolen
Lique M
LM
Strauss
Richelle
R
Jackman
Alana
A
Clegg
Deborah J
DJ
Seeley
Randy J
RJ
Woods
Stephen C
SC
D000818:Animals; D001835:Body Weight / Q000187:drug effects / Q000502:physiology; D001921:Brain / Q000187:drug effects* / Q000378:metabolism*; D004435:Eating / Q000187:drug effects; D007031:Hypothalamus / Q000166:cytology / Q000378:metabolism; D007150:Immunohistochemistry; D007276:Injections, Intraventricular; D007328:Insulin / Q000008:administration & dosage / Q000378:metabolism*; D008297:Male; D009074:Melanocyte-Stimulating Hormones / Q000037:antagonists & inhibitors / Q000378:metabolism* / Q000494:pharmacology; D009474:Neurons / Q000378:metabolism; D011333:Pro-Opiomelanocortin / Q000096:biosynthesis* / Q000235:genetics; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D020318:Rats, Long-Evans; D011972:Receptor, Insulin / Q000378:metabolism; D018043:Receptors, Corticotropin / Q000037:antagonists & inhibitors
D007328:Insulin; D012333:RNA, Messenger; D018043:Receptors, Corticotropin; C103272:SHU 9119; D011333:Pro-Opiomelanocortin; D009074:Melanocyte-Stimulating Hormones; D011972:Receptor, Insulin