| Budget Amount *help |
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2020: ¥390,000 (Direct Cost: ¥300,000、Indirect Cost: ¥90,000)
Fiscal Year 2019: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000)
Fiscal Year 2018: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2017: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
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| Outline of Final Research Achievements |
I have generated mice lacking β2-adrenergic receptors in skeletal muscle and found that skeletal muscle-specific β2 adrenergic receptor knockout mice were exercise non-responders. It showed that β2-adrenergic signaling plays an important role in metabolic adaptation during exercise. In addition, the increase in energy expenditure in response to β2-adrenergic stimuli was impaired in obese mice. These findings indicate that obesity triggers “adrenaline resistance”.
In skeletal muscle of obese animals, the expression of β2-adrenergic receptor (Adrb2) mRNA was reduced and the percentage of methylated CpG sites in the Adrb2 promoter was increased, which likely explain the mechanism of “adrenaline resistance”. Our data suggest that epigenetic regulation of Adrb2 is likely to contribute to the reduction of this gene in obese skeletal muscle, and dysregulation of β2-adrenergic signaling might be involved in the development of obesity.
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