Influence of the Trp64Arg polymorphism in the beta 3 adrenoreceptor gene on insulin resistance, adipocytokine response, and weight loss secondary to lifestyle modification in obese patients.
BACKGROUND
The aim of our study was to investigate the influence of the Trp64Arg polymorphism in the beta 3 adrenoreceptor gene on adipocytokine response, insulin resistance, and weight loss secondary to lifestyle modification (Mediterranean hypocaloric diet and exercise) in obese patients.


METHODS
A population of 65 obese (BMI >30) non-diabetic outpatients was analyzed in a prospective way. Before and after 3 months of a lifestyle modification program, indirect calorimetry, bioimpedance, blood pressure, serial assessment of nutritional intake for 3 days via written food records, and biochemical analysis were performed. The lifestyle modification program consisted of a hypocaloric diet (1520 kcal, 52% carbohydrates, 25% lipids, and 23% proteins). The exercise program consisted of an aerobic exercise at least three times a week (60 min each). The statistical analysis was performed for Trp64/Arg64 and Arg64/Arg64 combined as a mutant group and for type Trp64/Trp64 as a wild group.


RESULTS
The mean age of the study participants was 45.8+/-16.8 years and the mean BMI was 34.4+/-4.6 kg. There were 18 males (27.7%) and 47 females (72.3%). Fifty-five patients (84.6%; 15 males/40 females) had the Trp64/Trp64 genotype (wild group) and ten patients (15.4%; 3 males/7 females) had Trp64/Arg64 (mutant group). In the wild group, BMI, weight, fat mass, systolic blood pressure and waist circumference decreased. In this group, resting metabolic rate (RMR), RMR corrected by fat free mass, and VO(2) increased. In the mutant group, BMI, weight, fat mass, and waist circumference decreased. A significant increase was detected in RMR and VO(2) as well. No differences were detected between baseline values in the two groups. CRP levels were higher in the mutant group than in the wild variants. No differences were detected in other parameters. Only leptin levels decreased significantly in both the wild group (10.1%; p<0.05) and the mutant group (13.6; p<0.05).


CONCLUSIONS
This study showed that the beneficial effect of mild weight reduction by a low caloric diet and exercise program is the greatest in subjects with a normal homozygote beta 3 adrenoreceptor gene.
Institute of Endocrinology and Nutrition, Medicine School and Unit of Investigation, Hospital Rio Hortega, University of Valladolid, Valladolid, Spain.
D A
DA
de Luis
M
M
Gonzalez Sagrado
R
R
Aller
O
O
Izaola
R
R
Conde