Document Detail

Phenotypic and genetic variation in leptin as determinants of weight regain.
MedLine Citation:
PMID:  21042325     Owner:  NLM     Status:  MEDLINE    
AIMS: Over 75% of obese subjects fail to maintain their weight following weight loss interventions. We aimed to identify phenotypic and genetic markers associated with weight maintenance/regain following a dietary intervention.
SUBJECTS AND METHODS: In the 2-year Dietary Intervention Randomized Controlled Trial, we assessed potential predictors for weight changes during the 'weight loss phase' (0-6 months) and the 'weight maintenance/regain phase' (7-24 months). Genetic variation between study participants was studied using single-nucleotide polymorphisms in the leptin gene (LEP).
RESULTS: Mean weight reduction was -5.5% after 6 months, with a mean weight regain of 1.2% of baseline weight during the subsequent 7-24 months. In a multivariate regression model, higher baseline high-molecular-weight adiponectin was the only biomarker predictor of greater success in 0- to 6-month weight loss (β = -0.222, P-value = 0.044). In a multivariate regression model adjusted for 6-month changes in weight and various biomarkers, 6-month plasma leptin reduction exhibited the strongest positive association with 6-month weight loss (β = 0.505, P-value < 0.001). Conversely, 6-month plasma leptin reduction independently predicted weight regain during the following 18 months (β = -0.131, P-value < 0.013). Weight regain was higher among participants who had a greater (top tertiles) 6-month decrease in both weight and leptin (+3.4% (95% confidence interval 2.1-4.8)) as compared with those in the lowest combined tertiles (+0.2% (95% confidence interval -1.1 to 1.4)); P-value < 0.001. Weight regain was further significantly and independently associated with genetic variations in LEP (P = 0.006 for both rs4731426 and rs2071045). Adding genetic data to the phenotypic multivariate model increased its predictive value for weight regain by 34%.
CONCLUSION: Although greater reduction in leptin concentrations during the initial phase of a dietary intervention is associated with greater weight loss in the short term, plasma leptin reduction, combined with the degree of initial weight loss and with genetic variations in the LEP gene, constitutes a significant predictor of subsequent long-term weight regain.
G Erez; A Tirosh; A Rudich; V Meiner; D Schwarzfuchs; N Sharon; S Shpitzen; M Blüher; M Stumvoll; J Thiery; G M Fiedler; Y Friedlander; E Leitersdorf; E Leiterstdorf; I Shai
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Publication Detail:
Type:  Journal Article; Randomized Controlled Trial; Research Support, Non-U.S. Gov't     Date:  2010-11-02
Journal Detail:
Title:  International journal of obesity (2005)     Volume:  35     ISSN:  1476-5497     ISO Abbreviation:  Int J Obes (Lond)     Publication Date:  2011 Jun 
Date Detail:
Created Date:  2011-06-14     Completed Date:  2011-09-09     Revised Date:  2014-07-30    
Medline Journal Info:
Nlm Unique ID:  101256108     Medline TA:  Int J Obes (Lond)     Country:  England    
Other Details:
Languages:  eng     Pagination:  785-92     Citation Subset:  IM    
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MeSH Terms
Biological Markers / metabolism
Body Mass Index
Diet, Reducing / methods
Genetic Variation
Leptin / blood,  genetics*
Middle Aged
Obesity / genetics*,  metabolism
Weight Gain / genetics*,  physiology
Grant Support
//Biotechnology and Biological Sciences Research Council
Reg. No./Substance:
0/Biological Markers; 0/Leptin
Erratum In:
Int J Obes (Lond). 2012 Oct;36(10):1372

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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