Genetic polymorphisms of the renin-angiotensin system and obesity-related metabolic changes in response to low-energy diets in obese women.

OBJECTIVE: Genetic polymorphisms of the renin-angiotensin system have been implicated in cardiovascular and metabolic diseases. The purpose of this study was to investigate whether the insertion/deletion (I/D) polymorphism of the angiotensin-converting enzyme (ACE) gene and 3123C/A polymorphism of the angiotensin II type 2 receptor (AT(2)R) gene affect blood pressure and other obesity-related metabolic changes in response to low-energy diets using meal replacement shakes for weight loss. METHODS: Clinical, metabolic, and biochemical profiles were measured before and after a 2-mo intervention in 32 obese women (age 49.9 ± 8.4 [SD] y; BMI 28.4 ± 3.3 kg/m²) restricted to 1200 kcal/d (5021 kJ/d). The polymorphisms were determined with an intercalater-mediated FRET probe assay system. RESULTS: Although weight loss and nutrient intake levels did not differ among the genotypes, the reduction in body fat after weight loss was significantly less in the ACE deletion/deletion (D/D) genotype than insertion/insertion (I/I) plus I/D genotype (-2.25 ± 1.40% versus -0.80 ± 1.57%, P < 0.05). The AT2R A/A group had significantly less improved levels of systolic blood pressure (-7.23 ± 8.50 versus 2.50 ± 12.6 mmHg, P < 0.05), low-density lipoprotein-cholesterol (-0.36 ± 0.29 versus -0.09 ± 0.25 mmol/L, P < 0.05), carbohydrate (-54.4 ± 27.2 versus -31.8 ± 16.3 mg/min, P < 0.05) and fat oxidation (8.31 ± 11.86 versus 0.05 ± 9.99 mg/min, P < 0.05) than the C/C plus C/A genotypes. CONCLUSION: The present findings suggest that the homozygous form of the ACE gene may hinder the improvement of body fat and that the homozygous form of the AT2R gene may make improving systolic blood pressure and some obesity-related metabolic parameters through a dietary intervention difficult among obese women.

Low-calorie diet-induced reduction in serum HDL cholesterol is ameliorated in obese women with the -3826 G allele in the uncoupling protein-1 gene.

The uncoupling protein-1 (UCP1) gene is of major importance for regulation of body weight and lipid/lipoprotein metabolism. Our cross-sectional study has shown that subjects with the G/G genotype of the -3826 A/G polymorphism in the UCP-1 gene have higher levels of serum high-density lipoprotein cholesterol (HDL-C) than those with other genotypes. Low circulating HDL-C level has been regarded as a major atherosclerotic risk factor. We therefore investigated whether the -3826 A/G polymorphism affects the obesity- and lipid-related parameters during a low-calorie diet (LCD) intervention. In 32 obese women (49.9 +/- 8.4 years of age), anthropometric, physiological and biochemical characteristics were measured before and after a 2-month LCD treatment, which restricted each subject to the same energy intakes, such as 5,120 kJ/day. The -3826 A/G polymorphism was detected using a PCR-restriction fragment-length polymorphism method. There were 6 subjects with the A/A genotype, 15 with the A/G genotype and 11 with the G/G genotype. The LCD intervention decreased weight (P < 0.001) and serum HDL-C levels (P < 0.05) in all subjects. There was no difference in the levels of change in weight, nutrient intake, physiological measurements in energy expenditure, and fat oxidation between subjects with and without the G allele. In contrast, the degree of the reduction in the HDL-C levels was significantly smaller in subjects with the G allele than those without the G allele. These results suggest that the G allele at -3826 in the UCP1 gene may ameliorate the reduction in serum HDL-C levels in obese women during LCD.

Thermoregulatory sympathetic nervous system activity and diet-induced waist-circumference reduction in obese Japanese women.

The present study is designed to investigate how and to what extent sympathovagal behavior in a balanced low-calorie diet relates to favorable changes of body mass, waist circumference, and/or metabolic risk factors. The study involved 28 mildly obese women without clinical complications, who underwent an 8-week calorie restriction program using a 1,200-kcal daily diet with an adequate nutrient content; including two regular meals, and one formula meal replacement. All subjects were examined before and after the dietary intervention. We measured anthropometric parameters, blood pressure, and biochemical blood profiles for lipid metabolism. Autonomic nervous system activity was evaluated by heart rate variability power spectral analysis. The dietary intervention induced moderate, but significant reduction of waist circumference (-5.3% +/- 0.8%), body fat percentage (-5.8% +/- 0.8%), and body mass (-6.6% +/- 0.5%). Linear regression analysis showed that Deltavery low frequency (VLF) power reflecting energy metabolic- and thermoregulatory sympathetic function significantly correlated to Deltawaist circumference (r = -0.53, P < 0.01), Deltabody fat percentage (r = -0.39, P < 0.05), Deltabody mass (r = -0.43, P < 0.05), DeltaHDL-cholesterol/total cholesterol ratio (HDL-C/TC) (r = 0.62, P < 0.001), and Deltanonesterified fatty acids (NEFA) (r = 0.56, P < 0.01). A stepwise multiple regression analysis additionally revealed that Deltawaist circumference (P = 0.024), DeltaHDL-C/TC (P = 0.013), and DeltaNEFA (P = 0.016) were significant and independent factors, which contributing to the variance in DeltaVLF power (r(2) = 0.61). Although causes and consequences of obesity continue to elude researchers, the present study indicates that thermoregulatory sympathetic activity relates to moderate waist-circumference reduction together with favorable changes of blood lipid profiles after short-term dietary modification in mildly obese women.