期刊
AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM
卷 301, 期 1, 页码 E99-E104出版社
AMER PHYSIOLOGICAL SOC
DOI: 10.1152/ajpendo.00146.2011
关键词
muscle mass; fat-free mass; reproductive dysfunction
资金
- National Institutes of Health National Center for Research Resources [M01-RR-01032]
- National Institute of Diabetes and Digestive and Kidney Diseases [58785, 79929, 81913, AG-032030]
Brinkoetter M, Magkos F, Vamvini M, Mantzoros CS. Leptin treatment reduces body fat but does not affect lean body mass or the myostatin-follistatin-activin axis in lean hypoleptinemic women. Am J Physiol Endocrinol Metab 301: E99-E104, 2011. First published April 19, 2011; doi: 10.1152/ajpendo.00146.2011.-Animal studies in vivo indicate that leptin treatment in extremely leptin-sensitive ob/ob mice reduces body weight exclusively by reducing fat mass and that it increases muscle mass by downregulating myostatin expression. Data from human trials are limited. Therefore, we aimed at characterizing the effects of leptin administration on fat mass, lean body mass, and circulating regulators of muscle growth in hypoleptinemic and presumably leptin-sensitive human subjects. In an open-label, single-arm trial, seven lean, strenuously exercising, amenorrheic women with low leptin concentrations (<= 5 ng/ml) were given recombinant methionyl human leptin (metreleptin; 0.08 mg.kg(-1).day(-1)) for 10 wk. In a separate randomized, double-blind, placebo-controlled trial, seven women were given metreleptin (initial dose: 0.08 mg.kg(-1).day(-1) for 3 mo, increased thereafter to 0.12 mg.kg(-1).day(-1) if menstruation did not occur), and six were given placebo for 9 mo. Metreleptin significantly reduced total body fat by an average of 18.6% after 10 wk (P < 0.001) in the single-arm trial and by 19.5% after 9 mo (placebo subtracted; P for interaction = 0.025, P for metreleptin = 0.004) in the placebo-controlled trial. There were no significant changes in lean body mass (P >= 0.33) or in serum concentrations of myostatin (P >= 0.35), follistatin (P >= 0.30), and activin A (P >= 0.20) whether in the 10-wk trial or the 9-mo trial. We conclude that metreleptin administration in lean hypoleptinemic women reduces fat mass exclusively and does not affect lean body mass or the myostatin-follistatin-activin axis.
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