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Unlabelled: Calorie restriction (CR) delays the development of age-associated disease and increases lifespan in rodents, but the effects in humans remain uncertain., Purpose: Determine the effect of 6 months of CR with or without exercise on cardiovascular disease (CVD) risk factors and estimated 10-year CVD risk in healthy non-obese men and women., Methods: Thirty-six individuals were randomized to one of three groups for 6 months: Control, 100% of energy requirements; CR, 25% calorie restriction; CR+EX, 12.5% CR+12.5% increase in energy expenditure via aerobic exercise. CVD risk factors were assessed at baseline, 3 and 6 months., Results: After 6 months, CR and CR+EX lost approximately 10% of body weight. CR significantly reduced triacylglycerol (-31+/-15mg/dL) and factor VIIc (-10.7+/-2.3%). Similarly CR+EX reduced triacylglycerol (-22+/-8mg/dL) and additionally reduced LDL-C (-16.0+/-5.1mg/dL) and DBP (-4.0+/-2.1mmHg). In contrast, both triacylglycerol (24+/-14mg/dL) and factor VIIc (7.9+/-2.3%) were increased in the Control group. HDL-cholesterol was increased in all groups while hsCRP was lower in the Controls versus CR+EX. Estimated 10-year CVD risk significantly declined from baseline by 29% in CR (P<0.001) and 38% in the CR+EX (P<0.001) while remaining unchanged in the Control group., Conclusions: Based on combined favorable changes in lipid and blood pressure, caloric restriction with or without exercise that induces weight loss favorably reduces risk for CVD even in already healthy non-obese individuals.

Cholesterol ester transfer protein (CETP) facilitates reverse cholesterol transport via HDL-C and this activity may be increased in obese subjects. In normal weight subjects the Taq1B variant of the CETP gene is associated with lower CETP activity and higher HDL-C. The aim of this study was to examine the relationship between the Taq1B polymorphism and HDL-C in obese women before and after weight loss. A total of 245 women (41 with type 2 diabetes) were genotyped for the Taq1B variant. Plasma lipids, insulin, glucose and oral glucose tolerance were also measured before and after weight loss. When all subjects were examined together the Taq1B genotype was not associated with HDL-C. However, when non-diabetic subjects were divided by median fasting insulin, a strong linear association was observed between Taq1B genotype and HDL-C in subjects below median for fasting insulin (B1B1 1.19+/-0.07 mmol/l, B1B2 1.35+/-0.06, B2B2 1.71+/-0.09, P<0.000). This association was not observed in subjects with fasting insulin above median or subjects with type 2 diabetes, either before or after weight loss. Therefore, the B2B2 genotype is associated with elevated HDL-C in obese women with low fasting insulin only. Improved insulin sensitivity during weight loss did not change this relationship in women with high fasting insulin or type 2 diabetes.

Obesity is commonly associated with high rates of cardiovascular disease (CVD). Weight loss in obese subjects reduces risk factors for CVD but this response is not uniform. Genetic factors could be involved in this variability. The 360His polymorphism of apolipoproteinA-IV (apoA-IV) influences the lipid response to fat intake, but it is unclear whether this polymorphism could contribute to lipid variability during weight loss. Therefore, we assessed the effects of an energy restricted diet (6.3 MJ) for 12 weeks on weight loss and plasma lipids according to apoA-IV genotype in 186 overweight/obese subjects (BMI mean 33+/-4.3, range 25.0-48.0 kg/m(2)). The frequency of the 360His allele was 0.083. Energy restriction for 12 weeks resulted in an average weight loss of 8. 25+/-0.28 kg. HDL-C increased 5.4% in subjects with the apoA-IV-1/1 genotype with weight loss compared to a 2.6% decrease in apoA-IV-1/2 subjects (P=0.035). This was more apparent when only the subjects with type 2 diabetes (n=57) were analyzed (P=0.003). ApoA-IV genotype was not related to change in total cholesterol, LDL-C or triglyceride concentrations. Therefore, weight loss as a treatment to reduce CVD risk factors may be more effective in subjects with the apoA-IV-1/1 variant as compared to those with the apoA-IV-1/2 variant, especially in subjects with type 2 diabetes.