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: 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
• Journal: European journal of endocrinology (Eur J Endocrinol) Vol. 165 Issue 2 Pg. 249-54 (Aug 2011) ISSN: 1479-683X [Electronic] England
• PMID: 21602313 (Publication Type: Clinical Trial, Phase II, Journal Article, Randomized Controlled Trial, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Leptin
• Somatomedins
• Thyroid Hormones

Topics

• Adult
• Aged
• Caloric Restriction
• Diet, Reducing
• Drug Administration Schedule
• Female
• Humans
• Leptin (administration & dosage, blood)
• Male
• Middle Aged
• Obesity (blood, diet therapy, drug therapy)
• Osmolar Concentration
• Overweight (blood, diet therapy, drug therapy)
• Signal Transduction (drug effects)
• Somatomedins (analysis)
• Thyroid Gland (drug effects, metabolism)
• Thyroid Hormones (blood)
• Time Factors
• Weight Loss (drug effects)
• Young Adult