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

Greeshma K. Shetty, Giuseppe Matarese, Faidon Magkos, Hyun Seuk Moon, Xiaowen Liu, Aoife M. Brennan, Geetha Mylvaganam, Despina Sykoutri, Alex M. DePaoli, Christos S. Mantzoros

Research output: Contribution to journalArticle

34 Citations (Scopus)

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/m2) 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.

Original languageEnglish
Pages (from-to)249-254
Number of pages6
JournalEuropean Journal of Endocrinology
Volume165
Issue number2
DOIs
Publication statusPublished - Aug 2011

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Leptin
Thyroid Hormones
Weight Loss
Diet
Placebos
Hypothalamic Hormones
Pituitary Hormones
Anti-Idiotypic Antibodies
Body Mass Index
metreleptin
Serum

ASJC Scopus subject areas

  • Endocrinology
  • Endocrinology, Diabetes and Metabolism
  • Medicine(all)

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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. / Shetty, Greeshma K.; Matarese, Giuseppe; Magkos, Faidon; Moon, Hyun Seuk; Liu, Xiaowen; Brennan, Aoife M.; Mylvaganam, Geetha; Sykoutri, Despina; DePaoli, Alex M.; Mantzoros, Christos S.

In: European Journal of Endocrinology, Vol. 165, No. 2, 08.2011, p. 249-254.

Research output: Contribution to journalArticle

Shetty, Greeshma K. ; Matarese, Giuseppe ; Magkos, Faidon ; Moon, Hyun Seuk ; Liu, Xiaowen ; Brennan, Aoife M. ; Mylvaganam, Geetha ; Sykoutri, Despina ; DePaoli, Alex M. ; Mantzoros, Christos S. / 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. In: European Journal of Endocrinology. 2011 ; Vol. 165, No. 2. pp. 249-254.
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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/m2) 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.",
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T1 - 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

AU - Shetty, Greeshma K.

AU - Matarese, Giuseppe

AU - Magkos, Faidon

AU - Moon, Hyun Seuk

AU - Liu, Xiaowen

AU - Brennan, Aoife M.

AU - Mylvaganam, Geetha

AU - Sykoutri, Despina

AU - DePaoli, Alex M.

AU - Mantzoros, Christos S.

PY - 2011/8

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N2 - 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/m2) 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.

AB - 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/m2) 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.

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