| Budget Amount *help |
¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2003: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 2002: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 2001: ¥2,000,000 (Direct Cost: ¥2,000,000)
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| Research Abstract |
AIM : Both increased food intake and decreased energy expenditure are principal causes for the development of obesity. It is still controversial which is the predominant cause of the childhood obesity that has more genetic background than the adult obesity. In this study, genotypes of both β_3-adrenergic receptor (β_3AR) representing energy expenditure and melanocortin-4 receptor (MC4R) representing food intake were compared with phenotype of the childhood obesity.
SUBJECTS & METHODS : Thirty-five obese but otherwise healthy children (22 boys and 13 girls) who had shown overweight of more than 120% of the standard weight for their sex and height were enrolled in the study with informed consent. The boys and the girls showed ; age 10.2±3.4, 11.6±5.0 y/o, height 144.3±19.4, 143.7±15.5 cm, weight 59.0±20.9, 59.4±21.1 kg, BMI 27.4±4.2, 27.7±5.4, respectively. Using peripheral lymphocyte derived DNA, a Trp64Arg polymorphism for β_3AR was detected by the pinpoint-PCR method and the direct seq
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uencing of MC4R coding region was employed for mutation screening. Statistical analysis was performed by the non-parametric method.
RESULTS & DISCUSSION : Twenty-four of the 35 cases (68.6%) were homozygous (WW) for the wild type, 11 cases (31.4%) were heterozygous (WR) for both the wild and Trp64Arg alleles. Frequency of the Trp64Arg allele was 0.16, which was comparable to 0.16 the frequency seen in the general population in the eastern Asia and in Japan. Comparison between the WW and the WR groups made no difference in height, weight, BMI, alanine aminotransferase (ALT), total cholesterol, HDL-cholesterol and leptin level except a significantly (p<0.05) higher standard deviation (SD) of the body height in the WW group. These findings imply the Trp64Arg allele is less responsible for the development of childhood obesity for which tall stature is the characteristic feature. Furthermore, maximal weight gain since the onset of obesity was 9.3±4.3 kg/year in the study group, which was considerably greater than 2.7〜2.8kg/year the estimated weight gain through the decreased energy expenditure by the Trp64Arg mutation. These results may be suggestive to the predominance of the increased food intake over the decreased energy expenditure in regard to the etiology of the childhood obesity. As for the role of the MC4R, the fact that no mutation was found on MC4R in the obese subjects prompts us to investigate other factors than MC4R that would mutation was found on MC4R in the obese subjects prompts us to investigate other factors than MC4R that would regulate appetite and food intake as a candidate for the culprit of childhood obesity. Less
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