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  • Original Article
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Phenotypic and genetic variation in leptin as determinants of weight regain

International Journal of Obesity volume 35, pages 785–792 (2011)Cite this article

Subjects

A Corrigendum to this article was published on 09 October 2012

Abstract

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.

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Acknowledgements

We are thankful to the 322 Dietary Intervention Randomized Controlled Trial participants for their consistent cooperation. Sources of support: (1) The Israeli Ministry of Health, Chief Scientist Office (grants received by Drs Shai, Schwarzfuchs and Tirosh, Israel); (2) DFG grant (KFO 152, grants received by Drs Blüher and Stumvoll, Germany); (3) Sarah and Moshe Mayer Foundation for Research (grant received by Prof. Leitersdorf, Israel); and (4) The Dr Robert C and Veronica Atkins Research Foundation. This foundation was not involved in any stage of the design, conduct or analysis of the study and had no access to the study results before publication.

Author information

Author notes

  1. G Erez and A Tirosh: These authors contributed equally to this work.

Authors and Affiliations

  1. Obesity Clinic, Meuhedet Health Services, Jerusalem, Israel

    G Erez

  2. Division of Endocrinology, Diabetes, and Hypertension, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA

    A Tirosh

  3. Talpiot Medical Leadership Program, Chaim Sheba Medical Center, Tel-Hashomer, Israel

    A Tirosh

  4. The S. Daniel Abraham Center for Health and Nutrition, Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva, Israel

    A Rudich & I Shai

  5. Department of Human Genetics, Hadassah-University Hospital, Jerusalem, Israel

    V Meiner

  6. Nuclear Research Center Negev, Dimona, Israel

    D Schwarzfuchs

  7. Unit of Epidemiology, Hebrew University-Hadassah School of Public Health, Jerusalem, Israel

    N Sharon & Y Friedlander

  8. Center for Research, Prevention and Treatment of Atherosclerosis, Hadassah-University Hospital, Jerusalem, Israel

    S Shpitzen & E Leiterstdorf

  9. Department of Medicine, University of Leipzig, Leipzig, Germany

    M Blüher & M Stumvoll

  10. Institute of Laboratory Medicine, University of Leipzig, Leipzig, Germany

    J Thiery & G M Fiedler

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Correspondence to G Erez.

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Erez, G., Tirosh, A., Rudich, A. et al. Phenotypic and genetic variation in leptin as determinants of weight regain. Int J Obes 35, 785–792 (2011). https://doi.org/10.1038/ijo.2010.217

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