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.
Internal Medicine, University of Marburg, Marburg, Germany.
H L
HL
Fehm
R
R
Smolnik
W
W
Kern
G P
GP
McGregor
U
U
Bickel
J
J
Born
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)