The melanocortin melanocyte-stimulating hormone/adrenocorticotropin(4-10) decreases body fat in humans.
The control of body fat is a prominent factor in human health. Animal studies have indicated a homeostatic central nervous system regulation of body fat with particular involvement of the melanocortin receptor pathway. This study provides evidence for a similar role for melanocortins in the long-term control of fat stores in humans. Thirty-six normal weight humans were assigned to one of three experimental groups. After a 4-week baseline, one group was treated with MSH/ACTH(4-10) (MSH/ACTH(4-10)) representing the core sequence of all melanocortins. Another group received desacetyl-alphaMSH, a selective agonist of the brain melanocortin-4 receptor, which shares the 4-10 sequence with MSH/ACTH(4-10). The third group received placebo. Treatments were given intranasally twice daily for 6 weeks, at equimolar doses (MSH/ACTH(4-10), 0.5 mg; desacetyl-alphaMSH, 0.84 mg). Body weight, body composition, and plasma hormone concentrations were measured before and after treatment. MSH/ACTH(4-10) reduced body fat, on the average, by 1.68 kg (P < 0.05) and body weight by 0.79 kg (P < 0.001). Concurrently, plasma leptin levels were decreased by 24% (P < 0.02), and insulin levels were decreased by 20% (P< 0.05) after MSH/ACTH(4-10). Changes after desacetyl-alphaMSH remained nonsignificant. The finding of reduced body adiposity after MSH/ACTH(4-10) confirms and extends to the human the findings of animal models indicating an essential role of the hypothalamic melanocortin system in body weight control.
Fehm
H L
HL
Internal Medicine, University of Marburg, Marburg, Germany.
Smolnik
R
R
Kern
W
W
McGregor
G P
GP
Bickel
U
U
Born
J
J
D000273:Adipose Tissue / Q000187:drug effects*; D000324:Adrenocorticotropic Hormone / Q000008:administration & dosage / Q000494:pharmacology*; D000328:Adult; D001823:Body Composition / Q000187:drug effects*; D006801:Humans; D007328:Insulin / Q000097:blood; D020738:Leptin / Q000378:metabolism; D009074:Melanocyte-Stimulating Hormones / Q000008:administration & dosage / Q000494:pharmacology*; D010446:Peptide Fragments / Q000008:administration & dosage / Q000494:pharmacology*; D010919:Placebos; D044105:Receptor, Melanocortin, Type 4; D018000:Receptors, Peptide / Q000008:administration & dosage; D013963:Thyroid Hormones / Q000097:blood; D013972:Thyrotropin / Q000097:blood; D015431:Weight Loss / Q000187:drug effects; D000521:alpha-MSH / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology*
D007328:Insulin; D020738:Leptin; D010446:Peptide Fragments; D010919:Placebos; D044105:Receptor, Melanocortin, Type 4; D018000:Receptors, Peptide; D013963:Thyroid Hormones; D000521:alpha-MSH; D000324:Adrenocorticotropic Hormone; D013972:Thyrotropin; D009074:Melanocyte-Stimulating Hormones; C011394:ACTH (4-10)