title: Leptin treatment reduces body fat but does not affect lean body mass or the myostatin-follistatin-activin axis in lean hypoleptinemic women.
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 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.
authors.affiliation: Division of Endocrinology, Diabetes, and Metabolism, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts 02215, USA.
authors.forename: Mary
authors.initials: M
authors.lastname: Brinkoetter
authors.forename: Faidon
authors.initials: F
authors.lastname: Magkos
authors.forename: Maria
authors.initials: M
authors.lastname: Vamvini
authors.forename: Christos S
authors.initials: CS
authors.lastname: Mantzoros
mesh_terms: D028341:Activins / Q000097:blood / Q000378:metabolism* / Q000502:physiology; D000273:Adipose Tissue / Q000187:drug effects*; D000328:Adult; D001823:Body Composition / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects*; D004311:Double-Blind Method; D015536:Down-Regulation / Q000187:drug effects; D005260:Female; D038681:Follistatin / Q000097:blood / Q000378:metabolism* / Q000502:physiology; D006801:Humans; D020738:Leptin / Q000031:analogs & derivatives / Q000097:blood / Q000172:deficiency* / Q000627:therapeutic use*; D008659:Metabolic Diseases / Q000097:blood / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D055435:Myostatin / Q000097:blood / Q000378:metabolism* / Q000502:physiology; D010919:Placebos; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D013851:Thinness / Q000473:pathology; D055815:Young Adult
chemical_list: D038681:Follistatin; D020738:Leptin; D055435:Myostatin; D010919:Placebos; D028341:Activins; C415771:metreleptin