Leptin treatment reduces body fat but does not affect lean body mass or the myostatin-follistatin-activin axis in lean hypoleptinemic women
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Leptin treatment reduces body fat but does not affect lean body mass or the myostatin-follistatin-activin axis in lean hypoleptinemic women. / Brinkoetter, Mary; Magkos, Faidon; Vamvini, Maria; Mantzoros, Christos S.
In: American Journal of Physiology: Endocrinology and Metabolism, Vol. 301, No. 1, 2011, p. E99-E104.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - Leptin treatment reduces body fat but does not affect lean body mass or the myostatin-follistatin-activin axis in lean hypoleptinemic women
AU - Brinkoetter, Mary
AU - Magkos, Faidon
AU - Vamvini, Maria
AU - Mantzoros, Christos S
N1 - (Ekstern)
PY - 2011
Y1 - 2011
N2 - 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.
AB - 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.
KW - Activins/blood
KW - Adipose Tissue/drug effects
KW - Adult
KW - Body Composition/drug effects
KW - Body Weight/drug effects
KW - Double-Blind Method
KW - Down-Regulation/drug effects
KW - Female
KW - Follistatin/blood
KW - Humans
KW - Leptin/analogs & derivatives
KW - Metabolic Diseases/blood
KW - Myostatin/blood
KW - Placebos
KW - Signal Transduction/drug effects
KW - Thinness/pathology
KW - Young Adult
U2 - 10.1152/ajpendo.00146.2011
DO - 10.1152/ajpendo.00146.2011
M3 - Journal article
C2 - 21505147
VL - 301
SP - E99-E104
JO - American Journal of Physiology - Endocrinology and Metabolism
JF - American Journal of Physiology - Endocrinology and Metabolism
SN - 0193-1849
IS - 1
ER -
ID: 290458784