Additive effect of the mutations in the beta3-adrenoceptor gene and UCP3 gene promoter on body fat distribution and glycemic control after weight reduction in overweight subjects with CAD or metabolic syndrome.
OBJECTIVE
To analyze the effects of the mutations in the beta3-adrenoceptor (beta3-AR) gene and/or uncoupling protein3 (UCP3) gene promoter on body fat distribution and glycemic control after mild weight reduction in overweight-obese subjects with coronary artery disease (CAD) or metabolic syndrome.


METHODS
Clinical intervention study of the -300 kcal/day mild weight reduction program for 12 weeks.


METHODS
A total of 224 overweight-obese subjects with CAD or metabolic disorder, subdivided into the following four categories: (1) wild type (TT-CC, n=73); (2) only UCP3 promoter variant (TT-CT/TT, n=90); (3) only beta3-AR variant (TA/AA-CC, n=29); (4) both variants (TA/AA-CT/TT, n=32).


METHODS
Body mass index (BMI), blood pressure, calorie intakes, body fat distribution, serum glucose, insulin, free fatty acids, C-peptide and lipids before and after weight reduction.


RESULTS
After 12 weeks, all subjects lost approximately 5% of their initial body weight. Despite similar weight reduction, the highest decreases in abdominal adipose tissue at both L1 and L4 levels were observed in the 'wild-type' group (P<0.001) and the second highest in 'only UPC3 promoter variant' group (P<0.001). On the other hand, both variant-carriers had the smallest reduction only in visceral fat area at the L4 level. All subjects except both variant-carriers showed significant reductions in the fasting levels of glucose and FFA. The response areas of glucose (P<0.01) and insulin (P<0.05) were reduced largest in the 'wild-type' group and second largest in the 'UCP3 promoter variant' group.


CONCLUSIONS
All the four groups showed similar weight reduction after -300 kcal/d for 12 weeks. However, the beneficial effects on body fat distribution and glycemic control were greatest in the 'wild-type' group and smallest in 'both variants' group. In addition, these effects were less beneficial in carriers with beta3-AR gene variant than with UCP3 gene promoter variant.
Kim
O Y
OY
Yonsei University Research Institute of Science for Aging, Yonsei University, Seoul, Korea.
Cho
E Y
EY
Park
H Y
HY
Jang
Y
Y
Lee
J H
JH
D000273:Adipose Tissue / Q000473:pathology*; D001786:Blood Glucose / Q000378:metabolism; D002352:Carrier Proteins / Q000235:genetics*; D003327:Coronary Disease / Q000097:blood / Q000235:genetics; D004038:Diet, Reducing; D005260:Female; D005951:Glucose Tolerance Test; D006801:Humans; D007473:Ion Channels; D008055:Lipids / Q000097:blood; D008297:Male; D024821:Metabolic Syndrome / Q000097:blood / Q000235:genetics; D008875:Middle Aged; D024101:Mitochondrial Proteins; D009154:Mutation; D009765:Obesity / Q000178:diet therapy / Q000235:genetics* / Q000473:pathology; D011401:Promoter Regions, Genetic; D022702:Receptors, Adrenergic, beta-3 / Q000235:genetics*; D000071247:Uncoupling Protein 3; D015431:Weight Loss
D001786:Blood Glucose; D002352:Carrier Proteins; D007473:Ion Channels; D008055:Lipids; D024101:Mitochondrial Proteins; D022702:Receptors, Adrenergic, beta-3; C000604392:UCP3 protein, human; D000071247:Uncoupling Protein 3