Analysis of the pathogenic mechanisms of adrenaline resistance in skeletal muscle
| Project/Area Number |
17K09832
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Metabolomics
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| Research Institution | Kobe University |
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Principal Investigator |
Nomura Kazuhiro 神戸大学, 医学部附属病院, 特定助教 (70450236)
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| Project Period (FY) |
2017-04-01 – 2021-03-31
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| Project Status |
Completed (Fiscal Year 2020)
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| 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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| Keywords | 骨格筋 / 運動 / 肥満 / エネルギー代謝 / アドレナリンシグナル / エネルギー消費 / アドレナリン / 糖尿病 |
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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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| Academic Significance and Societal Importance of the Research Achievements |
肥満者ではエネルギー消費の減弱により、「より肥満しやすい状況」に陥るという悪循環を発症することが知られていたが、この分子機構は十分に明らかではなかった。今回見出した「肥満によって生じる骨格筋のアドレナリン抵抗性」という現象は、このような「肥満における悪循環」の形成メカニズムの一旦を担う可能性がある。本研究により、骨格筋のアドレナリンシグナルが全身の代謝制御に及ぼす影響とともに、骨格筋のアドレナリン抵抗性の病理的意義と発症機構が明らかとなれば、個体の代謝制御に関するより深い理解が得られるだけでなく、肥満を始めとした種々の代謝疾患に対する新規な治療法の開発に繋がる可能性もあり、その意義は大きい。
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Report
(5 results)
Research Products
(41 results)
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[Journal Article] Hyperglycemia induces skeletal muscle atrophy via a WWP1-KLF15 axis.2019
Author(s)
Hirata Y, Nomura K, Senga Y, Okada Y, Kobayashi K, Okamoto S, Minokoshi Y, Imamura M, Takeda S, Hosooka T, Ogawa W.
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Journal Title
JCI Insight.
Volume: 4
Issue: 4
Pages: 124952-124952
DOI
Related Report
Peer Reviewed / Open Access
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