Genetic variation at the leptin receptor gene locus may play an important role in the pathophysiology of human obesity, a leptin-resistant state. Previous studies exploring potential associations between leptin receptor gene polymorphisms and obesity have reported conflicting results. The aim of this study was to evaluate a genetically homogeneous population for associations between body composition variables and three common leptin receptor gene polymorphisms (K109R, Q223R, and K656N) that have potential functional significance as well as to assess the contributions of these polymorphisms to the variability of obesity. One hundred and eighteen consecutively enrolled subjects (62 women: mean age, 17.5 +/- 1.6 yr; body mass index range, 16.2-30.1; 56 men: mean age, 17.8 +/- 1.8 yr; body mass index range, 15.4-35.9) were genotyped for the three polymorphisms, and their body mass index, sum of 4 skinfolds, fat-free mass, percent fat mass, serum leptin levels, caloric intake, fat intake, and exercise patterns were determined. Allele frequencies were estimated by the gene-counting method, and genotype distributions between 89 normal weight (body mass index, < or =25 kg/m(2)) and 29 overweight-obese (body mass index, >25 kg/m(2)) subjects were compared using chi(2) test (using codominant, dominant, and recessive models). Analysis of covariance was also performed to evaluate associations between the polymorphisms and body composition variables after controlling for potential confounders. For the Q223R polymorphism, there was a higher prevalence of the R223 allele in the homozygous form among overweight-obese subjects vs. normal weight subjects (20.7% vs. 4.5%; P = 0.01). Furthermore, simple and multiple regression analyses revealed that the R223 allele in the homozygous form is a significant predictor of both body mass index (P = 0.015) and percent fat mass (P = 0.02) even after adjusting for age and gender and explains 4.5% of the variance in percent fat mass and 5% of the variance in body mass index. There was no significant difference in allele frequencies or genotype distributions for the K109R or K656N polymorphisms. These findings support the hypothesis that the Q223R polymorphism (but not the K109R or K656N polymorphism) of the leptin receptor gene is associated with obesity and predicts a small percentage of body weight and body composition variability in a genetically homogeneous population.

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Objective: We explored potential associations of two single nucleotide polymorphisms (SNPs) in the adiponectin gene (ADIPOQ; C45TOG, rs2241766 and C276GOT, rs1501299) with circulating total and high-molecular weight (HMW) adiponectin, insulin resistance (IR), and markers of obesity in a healthy Greek female population. Design and methods: The two SNPs were genotyped in 349 women without diabetes (mean age: 47.0G12.1 years, mean body mass index: 28.9G5.6 kg/m 2 ). Total and HMW adiponectin concentrations, body composition variables, IR parameters, and plasma lipid levels were determined. Results: In single SNP analysis adjusting for several potential confounders, SNP C276GOT was associated with higher fasting insulin levels (PZ0.01) and higher homeostasis model assessment index for IR (HOMA-IR; PZ0.009), and SNP C45TOG was associated with lower insulin levels and HOMA-IR (PZ0.05 and PZ0.07 respectively). No association with total or HMW adiponectin, plasma lipid levels, and body composition variables was observed; however, haplotype analysis revealed that subjects homozygous for the most common C45T/C276G haplotype had lower total adiponectin levels than did noncarriers of this haplotype (PZ0.02). The observed differences in HOMA-IR were very significant among women with a higher body fat (BF) percentage (R the population median of 41%; all P%0.005), but not among leaner individuals (P for interactions 0.01-0.07), thus suggesting that ADIPOQ effects on insulin sensitivity may depend upon BF status. Conclusion: Our data suggest a significant role of ADIPOQ variants at positions C45 and C276 in the development of IR in healthy Greek women possibly through an interaction with BF.

YANNAKOULIA, M., LABROS MELISTAS, ELENI SOLOMOU, AND NIKOS YIANNAKOURIS. Association of eating frequency with body fatness in pre-and postmenopausal women. Obesity. 2007;15:100 -106. Objective: To examine associations between eating frequency (EF) and body fatness in pre-and postmenopausal women, after excluding potential low-energy reporters. Research Methods and Procedures:In this cross-sectional study of 220 free-living women, 64 pre-and 50 postmenopausal non-low-energy-reporting women were further analyzed (age, 24 to 74 years; BMI, 18.5 to 38.6 kg/m 2 ). Anthropometric and body composition measurements (DXA) were performed in all study participants. EF, energy, and macronutrient intake were assessed by 3-day food record. Physical activity level and energy expenditure were assessed by self-reported questionnaire. Results: No association between EF and adiposity indices was detected in premenopausal women. In contrast, EF was positively correlated with percentage body fat in postmenopausal women (r ϭ 0.30, p ϭ 0.03). EF was positively correlated with total energy intake in both groups and with total energy expenditure in premenopausal women only (r ϭ 0.34, p ϭ 0.02). Multivariate analysis revealed that, in postmenopausal women, EF was a significant predictor of body fatness (standardized ␤ ϭ 0.41, p ϭ 0.01). Discussion: Frequent eating was not found to be related to adiposity in premenopausal women, but it was associated with increased body fat in postmenopausal women. Possible explanations could be that the frequent eating is not associated with a physically active lifestyle in postmenopausal women or that frequent eating predisposes women after menopause to a higher energy intake by increasing food stimuli and rendering it more difficult for them to control energy balance.

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