Overweight humans are resistant to the weight-reducing effects of melanocortin4-10.
BACKGROUND
By enhancing energy expenditure and suppressing appetite, melanocortin peptides derived from proopiomelanocortin play a primary role in the hypothalamic regulation of body weight. In a recent study in normal-weight adults, the 6-wk intranasal administration of the MSH/ACTH(4-10) core fragment of proopiomelanocortin resulted in a distinct reduction of body weight and body fat, accompanied by significant decreases in leptin and insulin plasma concentrations.


OBJECTIVE
The present study aimed to generalize this finding to overweight patients.


METHODS
MSH/ACTH(4-10) (0.5 mg) and placebo were intranasally administered once in the morning and once in the evening over a period of 12 wk in 23 overweight men (body mass index, mean +/- sem: 29.72 +/- 0.43 kg/m(2)).


RESULTS
MSH/ACTH(4-10) did not induce any significant reduction in body weight, body fat, and plasma levels of insulin and leptin as compared with the effects of placebo. Melanocortin treatment was accompanied by reduced cortisol concentrations.


CONCLUSIONS
We conclude that contrasting with normal-weight humans, overweight subjects are not susceptible to the effects of melanocortin administration on hypothalamic weight regulatory systems. In overweight subjects, a decreased sensitivity to ACTH/MSH peptides may derive from alterations at the level of the melanocortin receptor or at subsequent steps in the processing of the body fat signal.
Hallschmid
Manfred
M
Department of Neuroendocrinology, University of Lübeck, Ratzeburger Allee 160, Haus 23, 23538 Lübeck, Germany.
Smolnik
Rüdiger
R
McGregor
Gerard
G
Born
Jan
J
Fehm
Horst L
HL
D000281:Administration, Intranasal; D000324:Adrenocorticotropic Hormone / Q000008:administration & dosage / Q000097:blood / Q000494:pharmacology*; D000328:Adult; D001823:Body Composition / Q000187:drug effects*; D001835:Body Weight / Q000187:drug effects*; D004311:Double-Blind Method; D004351:Drug Resistance; D006801:Humans; D006854:Hydrocortisone / Q000097:blood; D007328:Insulin / Q000097:blood; D020738:Leptin / Q000097:blood; D008297:Male; D008875:Middle Aged; D050177:Overweight / Q000187:drug effects* / Q000502:physiology; D010446:Peptide Fragments / Q000008:administration & dosage / Q000097:blood / Q000494:pharmacology*
D007328:Insulin; D020738:Leptin; D010446:Peptide Fragments; D000324:Adrenocorticotropic Hormone; C011394:ACTH (4-10); D006854:Hydrocortisone