Fehm H L, Smolnik R, Kern W, McGregor G P, Bickel U, Born J
Internal Medicine, University of Marburg, Marburg, Germany.
J Clin Endocrinol Metab. 2001 Mar;86(3):1144-8. doi: 10.1210/jcem.86.3.7298.
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.
控制体脂是人类健康的一个重要因素。动物研究表明，中枢神经系统通过黑皮质素受体途径对体脂进行稳态调节。本研究为黑皮质素在人类长期控制脂肪储存中发挥类似作用提供了证据。36名体重正常的人被分配到三个实验组之一。在4周的基线期后，一组接受代表所有黑皮质素核心序列的促黑素细胞激素/促肾上腺皮质激素（4-10）（MSH/ACTH(4-10)）治疗。另一组接受去乙酰化α-促黑素细胞激素，它是脑黑皮质素-4受体的选择性激动剂，与MSH/ACTH(4-10)共享4-10序列。第三组接受安慰剂。治疗为期6周，每天经鼻给药两次，剂量为等摩尔剂量（MSH/ACTH(4-10)，0.5毫克；去乙酰化α-促黑素细胞激素，0.84毫克）。在治疗前后测量体重、身体成分和血浆激素浓度。MSH/ACTH(4-10)平均使体脂减少1.68千克（P < 0.05），体重减少0.79千克（P < 0.001）。同时，MSH/ACTH(4-10)治疗后血浆瘦素水平降低24%（P < 0.02），胰岛素水平降低20%（P < 0.05）。去乙酰化α-促黑素细胞激素治疗后的变化无统计学意义。MSH/ACTH(4-10)治疗后体脂减少的发现证实并将动物模型的研究结果扩展至人类，表明下丘脑黑皮质素系统在体重控制中起重要作用。
