Hypothalamic pro-opiomelanocortin mRNA is reduced by fasting and [corrected] 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 can produce satiety, raising the possibility that alpha-MSH may mediate physiological satiety signals. Since alpha-MSH is coded for by the pro-opiomelanocortin (POMC) gene, we examined if POMC gene expression would be inhibited by fasting in normal mice or in models of obesity characterized 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, compared 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 neuropeptide Y (NPY) and melanin-concentrating hormone (MCH) mRNA. Finally, treatment of both male and female ob/ob mice with leptin stimulated hypothalamic POMC mRNA by about threefold. These results suggest that 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 melanocortin system.
Mizuno
T M
TM
Fishberg Center for Neurobiology, Department of Geriatrics, Mount Sinai School of Medicine, New York, New York 10029-6574, USA.
Kleopoulos
S P
SP
Bergen
H T
HT
Roberts
J L
JL
Priest
C A
CA
Mobbs
C V
CV
D000818:Animals; D015152:Blotting, Northern; D004351:Drug Resistance; D005215:Fasting; D005260:Female; D015870:Gene Expression; D007028:Hypothalamic Hormones / Q000235:genetics; D007031:Hypothalamus / Q000378:metabolism*; D020738:Leptin; D008297:Male; D008543:Melanins / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D008820:Mice, Obese; D009478:Neuropeptide Y / Q000235:genetics; D009765:Obesity / Q000378:metabolism*; D010907:Pituitary Hormones / Q000235:genetics; D011506:Proteins / Q000494:pharmacology*; D012333:RNA, Messenger / Q000378:metabolism*
D007028:Hypothalamic Hormones; D020738:Leptin; D008543:Melanins; D009478:Neuropeptide Y; D010907:Pituitary Hormones; D011506:Proteins; D012333:RNA, Messenger; C019463:melanin-concentrating hormone