title: Leptin administration to overweight and obese subjects for 6 months increases free leptin concentrations but does not alter circulating hormones of the thyroid and IGF axes during weight loss induced by a mild hypocaloric diet.
abstract: OBJECTIVE
  Short-term energy deprivation reduces leptin concentrations and alters the levels of circulating hormones of the hypothalamic-pituitary-peripheral axis in lean subjects. Whether the reduction in leptin concentration during long-term weight loss in obese individuals is linked to the same neuroendocrine changes seen in lean, leptin-sensitive subjects remains to be fully clarified.
  
  
  METHODS
  In this study, 24 overweight and obese adults (16 women and eight men; body mass index (BMI): 27.5-38.0 kg/m(2)) were prescribed a hypocaloric diet (-500 kcal/day) and were randomized to receive recombinant methionyl leptin (n=18, metreleptin, 10 mg/day self-injected s.c.) or placebo (n=6, same volume and time as metreleptin) for 6 months.
  
  
  RESULTS
  Metreleptin administration did not affect weight loss beyond that induced by hypocaloric diet alone (P for interaction=0.341) but increased the serum concentrations of total leptin by six- to eight-fold (P<0.001) and led to the generation of anti-leptin antibodies. Despite free leptin concentration (P for interaction=0.041) increasing from 9±1 ng/ml at baseline to 43±15 and 36±12 ng/ml at 3 and 6 months, respectively, changes in circulating hormones of the thyroid and IGF axes at 3 and 6 months were not significantly different in the placebo- and metreleptin-treated groups.
  
  
  CONCLUSIONS
  Leptin does not likely mediate changes in neuroendocrine function in response to weight loss induced by a mild hypocaloric diet in overweight and obese subjects.
authors: Division of Endocrinology, Diabetes and Metabolism, Harvard Medical School and Harvard School of Public Health, Beth Israel Deaconess Medical Center, 330 Brookline Avenue, Boston, Massachusetts 02215, USA.
authors: Greeshma K
authors: GK
authors: Shetty
authors: Giuseppe
authors: G
authors: Matarese
authors: Faidon
authors: F
authors: Magkos
authors: Hyun-Seuk
authors: HS
authors: Moon
authors: Xiaowen
authors: X
authors: Liu
authors: Aoife M
authors: AM
authors: Brennan
authors: Geetha
authors: G
authors: Mylvaganam
authors: Despina
authors: D
authors: Sykoutri
authors: Alex M
authors: AM
authors: Depaoli
authors: Christos S
authors: CS
authors: Mantzoros
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