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The -3826 AG Variant of the Uncoupling Protein-1 Gene Diminishes Postprandial Thermogenesis after a High Fat Meal in Healthy Boys

Laboratory of Applied Physiology, Graduate School of Human and Environmental Studies, Kyoto University (N.N., L.M.U., T.H., T.M.), Kyoto 606-8501, Japan; Department of Nutritional Science, Okayama Prefectural University (N.N.), Okayama 719-1197, Japan; and Center for Endocrine and Metabolic Disease, Kyoto National Hospital (N.S.), Kyoto 612-8555, Japan

Address all correspondence and requests for reprints to: Dr. Toshio Moritani, Laboratory of Applied Physiology, Graduate School of Human and Environmental Studies, Kyoto University, Sakyo-ku, Kyoto 606-8501, Japan. E-mail: t.moritani{at}neuro.mbox.media.kyoto-u.ac.jp.

This study investigated whether the -3826 AG nucleotide variant of the uncoupling protein-1 (UCP1) gene is correlated with postprandial thermogenesis after a high fat meal in children. Healthy boys, aged 8–11 yr, were examined for resting energy expenditure and the thermic effect of a meal (TEM), which were measured by indirect calorimetry for 180 min after a high fat (70% fat, 20% carbohydrate, and 10% protein, providing 30% of the daily energy requirement) and a high carbohydrate meal (20% fat, 70% carbohydrate, and 10% protein). The sympatho-vagal activities were assessed by means of spectral analysis of the heart rate variability during the same period. Children were genotyped for UCP1 polymorphism by applying a PCR-restriction fragment length polymorphism using buccal samples. There was no reaction of sympathetic activity to the high carbohydrate meal in eitherthe GG allele or the AA+AG group and no significant difference in TEM. However, after the high fat meal, sympathetic responses were found in both groups; further, the GG allele group showed significantly lower TEM than the AA+AG group. In conclusion, despite fat-induced sympathetic stimulation, GG allele carriers have a lowered capacity of TEM in response to fat intake, suggesting that such impaired UCP1-linked thermogenesis can have adverse effects on the regulation of body weight.

This work was supported by a Japanese Ministry of Education, Science, Sports, and Culture Grant-in-Aid for Scientific Research (B 11480011).

Abbreviations: BAT, Brown adipose tissue; ECG, electrocardiogram; EE, energy expenditure; SNS, sympathetic nervous system; TEM, thermic effect of meal; UCP1, uncoupling protein-1.