Phenotypic and genetic variation in leptin as determinants of weight regain

被引:43
作者
Erez, G. [1 ]
Tirosh, A. [2 ,3 ,4 ]
Rudich, A. [5 ]
Meiner, V. [6 ]
Schwarzfuchs, D. [7 ]
Sharon, N. [8 ]
Shpitzen, S. [9 ]
Blueher, M. [10 ]
Stumvoll, M. [10 ]
Thiery, J. [11 ]
Fiedler, G. M. [11 ]
Friedlander, Y. [8 ]
Leiterstdorf, E. [9 ]
Shai, I. [5 ]
机构
[1] Meuhedet Hlth Serv, Obes Clin, IL-90805 Jerusalem, Mevaseret Zion, Israel
[2] Brigham & Womens Hosp, Div Endocrinol Diabet & Hypertens, Boston, MA 02115 USA
[3] Harvard Univ, Sch Med, Boston, MA USA
[4] Chaim Sheba Med Ctr, Talpiot Med Leadership Program, IL-52621 Tel Hashomer, Israel
[5] Ben Gurion Univ Negev, Fac Hlth Sci, S Daniel Abraham Ctr Hlth & Nutr, Beer Sheva, Israel
[6] Hadassah Univ Hosp, Dept Human Genet, IL-91120 Jerusalem, Israel
[7] Nucl Res Ctr Negev, Dimona, Israel
[8] Hebrew Univ Jerusalem Hadassah Hosp & Med Sch, Sch Publ Hlth, Epidemiol Unit, Jerusalem, Israel
[9] Hadassah Univ Hosp, Ctr Res Prevent & Treatment Atherosclerosis, IL-91120 Jerusalem, Israel
[10] Univ Leipzig, Dept Med, Leipzig, Germany
[11] Univ Leipzig, Inst Lab Med, Leipzig, Germany
关键词
leptin; genetic polymorphism; weight maintenance; LIFE-STYLE INTERVENTION; SEQUENCE VARIANTS; SKELETAL-MUSCLE; BLOOD-PRESSURE; SERUM LEPTIN; OBESITY; HYPERTENSION; MAINTENANCE; REDUCTION; RESPONSES;
D O I
10.1038/ijo.2010.217
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
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 (beta = -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 (beta - 0.505, P-value < 0.001). Conversely, 6-month plasma leptin reduction independently predicted weight regain during the following 18 months (beta = -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. International Journal of Obesity (2011) 35, 785-792; doi:10.1038/ijo.2010.217; published online 2 November 2010
引用
收藏
页码:785 / 792
页数:8
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