The melanocortin melanocyte-stimulating hormone/adrenocorticotropin(4-10) decreases body fat in humans

• Published in: The journal of clinical endocrinology and metabolism Vol. 86; no. 3; pp. 1144 - 1148
• Main Authors: Fehm, H L, Smolnik, R, Kern, W, McGregor, G P, Bickel, U, Born, J
• Format: Journal Article
• Language: English
• Published: United States 01.03.2001
• Subjects: Adipose Tissue - drug effects; Adrenocorticotropic Hormone - administration & dosage; Adrenocorticotropic Hormone - pharmacology; Adult; alpha-MSH - administration & dosage; alpha-MSH - analogs & derivatives; alpha-MSH - pharmacology; Body Composition - drug effects; Humans; Insulin - blood; Leptin - metabolism; Melanocyte-Stimulating Hormones - administration & dosage; Melanocyte-Stimulating Hormones - pharmacology; Peptide Fragments - administration & dosage; Peptide Fragments - pharmacology; Placebos; Receptor, Melanocortin, Type 4; Receptors, Peptide - administration & dosage; Thyroid Hormones - blood; Thyrotropin - blood; Weight Loss - drug effects
• ISSN: 0021-972X
• DOI: 10.1210/jc.86.3.1144

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.