Aim: Polymorphisms in uncoupling protein (UCP) genes have been strongly associated with energy expenditure and obesity. This study aimed at investigating the effects of UCP gene polymorphisms (UCP1 -3826A/G, UCP2A/V, UCP2 I/D, and UCP3 -55C/T) on change in body mass index (BMI) during a lifestyle modification program in Japanese subjects. Results: Intervention induced a significant decrease in energy intake ( -8.6% -17.0%) and a significant increase in energy expenditure (7.7% -7.4%). As a result, participants experienced a significant decrease in their BMI of -1.8% -2.7%. In a multivariate regression analysis, only UCP2 D/I among the selected UCP gene polymorphisms was associated with a change in BMI independent of the effects of gender, age, baseline BMI, changes in energy intake, and expenditure. Further regression analysis revealed that, in contrast to the DD genotype group, the DI + II genotype group showed no significant association between weight loss and change in energy expenditure suggesting this polymorphism altered the effects of this parameter on change in BMI. Conclusion: The study found UCP2 D/I to be associated with change in BMI by altering the effect of change in energy expenditure on change in BMI.

BACKGROUND/OBJECTIVEApolipoprotein A5 gene promoter region T-1131C polymorphism (APOA5 T-1131C) is known to be associated with elevated plasma TG levels, although little is known of the influence of the interaction between APOA5 T-1131C and lifestyle modification on TG levels. To investigate this matter, we studied APOA5 T-1131C and plasma TG levels of subjects participating in a three-month lifestyle modification program.SUBJECTS/METHODSA three-month lifestyle modification program was conducted with 297 participants (Age: 57 ± 8 years) in Izumo City, Japan, from 2001-2007. Changes in energy balance (the difference between energy intake and energy expenditure) and BMI were used to evaluate the participants' responses to the lifestyle modification.RESULTSEven after adjusting for confounding factors, plasma TG levels were significantly different at baseline among three genotype subgroups: TT, 126 ± 68 mg/dl; TC, 134 ± 74 mg/dl; and CC, 172 ± 101 mg/dl. Lifestyle modification resulted in significant reductions in plasma TG levels in the TT, TC, and CC genotype subgroups: -21.9 ± 61.0 mg/dl, -20.9 ± 51.0 mg/dl, and -42.6 ± 78.5 mg/dl, respectively, with no significant differences between them. In a stepwise regression analysis, age, APOA5 T-1131C, body mass index (BMI), homeostasis model assessment-insulin resistance (HOMA-IR), and the 18:1/18:0 ratio showed independent association with plasma TG levels at baseline. In a general linear model analysis, APOA5 T-1131C C-allele carriers showed significantly greater TG reduction with decreased energy balance than wild type carriers after adjustment for age, gender, and baseline plasma TG levels.CONCLUSIONSThe genetic effects of APOA5 T-1131C independently affected plasma TG levels. However, lifestyle modification was effective in significantly reducing plasma TG levels despite the APOA5 T-1131C genotype background.

MC4R rs17782313 was associated with obesity and could confer a certain susceptibility to T2D that could be independent of its pro-obesity effect.

Aim:The aim of this study was to investigate the association of cannabinoid receptor 1 (CNR1) 4895 C/T gene polymorphism with obesity and obesity-related cardiovascular disease (CVD) risk factors in Japanese. Method: This study included 1,452 Japanese (678 men and 774 women, aged 25 to 74) from rural communities in Shimane Prefecture, Japan. Results: The frequency of the C minor allele of CNR1 4895 C/T polymorphism was 47%. In men, the CC genotype carriers showed significantly greater body mass index (BMI) and waist circumference (WC) values than T allele carriers, even after adjusting for age and medications for hypertension, dyslipidemia and type 2 diabetes. The frequency of obesity (BMI ≥ 25 kg/m 2 ) in CC genotype carriers was significantly greater than in T allele carriers (31.8% vs 21.5%), but the frequency of central obesity (WC ≥ 85 for men and WC ≥ 90 cm for women) was not significant by CNR1 4895 C/T genotype. CC genotype carriers of CNR1 4895 C/T showed, in logistic regression analysis, significantly greater odds for obesity than T allele carriers, even after adjustment for age and the abovementioned medications. Systolic blood pressure (SBP) values were also significantly different between the CC genotype and T allele carriers after controlling for age, medications for hypertension, dyslipidemia, and type 2 diabetes, and BMI or WC. Conclusion: This study supports the association of CNR1 4895 C/T with interindividual differences in obesity in men.