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Relation of weight maintenance and dietary restraint to peroxisome proliferator–activated receptor 2, glucocorticoid receptor, and ciliary neurotrophic factor polymorphisms^1,2,3

¹ From the Departments of Human Biology (NV, ECMM, FGB, KD, and MSW-P) and Methodology and Statistics (ADMK), Maastricht University, Maastricht, Netherlands

Background: Genetic variation in the peroxisome proliferator–activated receptor 2 (PPAR2), glucocorticoid receptor (GRL), and ciliary neurotrophic factor (CNTF) genes may play a role in the etiology of obesity.

Objective: We examined biological, psychological, and genetic determinants associated with weight maintenance (WM) after weight loss.

Design: Subjects (n = 120) followed a 6-wk diet and then a 1-y period of WM. Body weight (BW), body composition, leptin concentration, attitude toward eating (measured with the Three-Factor Eating Questionnaire), physical activity, and the polymorphisms of the PPAR2, GRL, and CNTF genes were measured.

Results: BW loss was 7.0 ± 3.1 kg. After 1 y, 21 subjects showed successful WM (<10% regain); 99 were unsuccessful (10% regain). Compared with unsuccessful subjects, successful subjects had a higher increase in dietary restraint over time (4.8 ± 5.0 and 1.8 ± 3.9, respectively; P < 0.01) but significantly less sensation of general hunger (–4.0 ± 4.9 and –1.2 ± 2.7, respectively; P < 0.05). Successful subjects had a significantly different frequency distribution for the PPAR2 (P = 0.05) and GRL (P < 0.05) genes than did unsuccessful subjects. The more successful genotypes showed a higher baseline body mass index and waist circumference (PPAR2), a greater decrease in disinhibition of dietary restraint (GRL), and less sensation of hunger (GRL). The G/G genotype (GRL) was an independent predictor of successful WM.

Conclusion: The different genotypes of the PPAR2 and GRL genes contribute to WM, either directly (GRL) or indirectly (PPAR2 and GRL) via baseline body mass index and waist circumference, and to changes in Three-Factor Eating Questionnaire scores.

Key Words: Obesity • body weight loss • weight maintenance • dietary restraint • peroxisome proliferator–activated receptor 2 • PPAR2 • glucocorticoid receptor • GRL

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