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Am J Physiol Endocrinol Metab. 2011 Apr 19. [Epub ahead of print]
Leptin treatment may reduce body fat but does not affect lean body mass or the myostatin-follistatin-activin axis in lean hypoleptinemic women.
Brinkoetter M, Magkos F, Vamvini M, Mantzoros CS.
Source
1Harvard Medical School / Beth Israel Deaconess Medical Center.
Abstract
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 down-regulating myostatin expression. Data from human trials are limited. We therefore 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•day) for 10 weeks. In a separate randomized, double-blind, placebo-controlled trial, seven women were given metreleptin (initial dose: 0.08 mg/kg•day for 3 months; increased thereafter to 0.12 mg/kg per day if menstruation did not occur) and six were given placebo for 9 months. Metreleptin significantly reduced total body fat by an average of 18.6% after 10 weeks (P<0.001) in the single-arm trial, and by 19.5% after 9 months (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-week trial or the 9-month trial. We conclude that metreleptin administration in lean hypoleptinemic women reduces exclusively fat mass and does not affect lean body mass or the myostatin-follistatin-activin axis.
PMID:
21505147
[PubMed - as supplied by publisher]
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