Satiety effect and sympathetic activation of leptin are mediated by hypothalamic melanocortin system.
Leptin is an adipocyte-derived blood-borne satiety factor that decreases food intake and increases energy expenditure, thereby leading to a substantial decrease in body weight. To explore the possible roles of the hypothalamic melanocortin system in leptin action, we examined the effects of intracerebroventricular (i.c.v.) injection of leptin with or without SHU9119, a potent antagonist of alpha-melanocyte stimulating hormone, on food intake, body weight, and mitochondrial uncoupling protein-1 (UCP-1) mRNA expression in the brown adipose tissue (BAT) in rats. A single i.c.v. injection of leptin decreased cumulative food intake and body weight gain, and increased UCP-1 mRNA expression during 3 h at the onset of the dark phase. Inhibition of food intake and body weight change with leptin was reversed by co-injection of SHU9119 in a dose-dependent manner. Co-injection of SHU9119 also inhibited completely the leptin-induced increase in UCP-1 mRNA expression in the BAT. Treatment with SHU9119 alone did not affect food intake, body weight, and UCP-1 mRNA expression in rats. The present study provides evidence that the hypothalamic melanocortin system plays a central role in both satiety effect and sympathetic activation of leptin.
Department of Medicine and Clinical Science, Kyoto University Graduate School of Medicine, Japan.
N
N
Satoh
Y
Y
Ogawa
G
G
Katsuura
Y
Y
Numata
H
H
Masuzaki
Y
Y
Yoshimasa
K
K
Nakao
D002001:Adipose Tissue, Brown / Q000378:metabolism; D000818:Animals; D015152:Blotting, Northern; D001835:Body Weight / Q000187:drug effects; D002352:Carrier Proteins / Q000235:genetics; D004305:Dose-Response Relationship, Drug; D004435:Eating / Q000187:drug effects*; D007031:Hypothalamus / Q000502:physiology*; D007276:Injections, Intraventricular; D007473:Ion Channels; D020738:Leptin; D008297:Male; D009074:Melanocyte-Stimulating Hormones / Q000008:administration & dosage / Q000494:pharmacology; D008565:Membrane Proteins / Q000235:genetics; D024101:Mitochondrial Proteins; D011506:Proteins / Q000008:administration & dosage / Q000494:pharmacology*; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D018043:Receptors, Corticotropin / Q000037:antagonists & inhibitors; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000494:pharmacology; D012528:Satiety Response / Q000187:drug effects; D000071256:Uncoupling Protein 1; D000521:alpha-MSH / Q000037:antagonists & inhibitors
D002352:Carrier Proteins; D007473:Ion Channels; D020738:Leptin; D008565:Membrane Proteins; D024101:Mitochondrial Proteins; D011506:Proteins; D012333:RNA, Messenger; D018043:Receptors, Corticotropin; D011994:Recombinant Proteins; C000604373:Ucp1 protein, rat; D000071256:Uncoupling Protein 1; C103272:SHU 9119; D000521:alpha-MSH; D009074:Melanocyte-Stimulating Hormones