Document Detail


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.
MedLine Citation:
PMID:  21602313     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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
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Publication Detail:
Type:  Clinical Trial, Phase II; Journal Article; Randomized Controlled Trial; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2011-05-20
Journal Detail:
Title:  European journal of endocrinology / European Federation of Endocrine Societies     Volume:  165     ISSN:  1479-683X     ISO Abbreviation:  Eur. J. Endocrinol.     Publication Date:  2011 Aug 
Date Detail:
Created Date:  2011-07-12     Completed Date:  2011-09-09     Revised Date:  2012-03-21    
Medline Journal Info:
Nlm Unique ID:  9423848     Medline TA:  Eur J Endocrinol     Country:  England    
Other Details:
Languages:  eng     Pagination:  249-54     Citation Subset:  IM    
Affiliation:
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.
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MeSH Terms
Descriptor/Qualifier:
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
Grant Support
ID/Acronym/Agency:
AG032030/AG/NIA NIH HHS; DK081913/DK/NIDDK NIH HHS; DK58785/DK/NIDDK NIH HHS; DK79929/DK/NIDDK NIH HHS; F32 DK64550-01A1/DK/NIDDK NIH HHS; GJT08004//Telethon; K24 DK081913-03/DK/NIDDK NIH HHS; R01 AG032030-03/AG/NIA NIH HHS; R01 AG032030-04/AG/NIA NIH HHS; R01 DK058785-02/DK/NIDDK NIH HHS; R01 DK079929-03/DK/NIDDK NIH HHS
Chemical
Reg. No./Substance:
0/Leptin; 0/Somatomedins; 0/Thyroid Hormones

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