2021 Fiscal Year Final Research Report

Mechano-nutrition-signaling for disuse muscle atrophy

Research Project

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Project/Area Number	19H04054
Research Category	Grant-in-Aid for Scientific Research (B)
Allocation Type	Single-year Grants
Section	一般
Review Section	Basic Section 59040:Nutrition science and health science-related
Research Institution	The University of Tokushima
Principal Investigator	NIKAWA Takeshi 徳島大学, 大学院医歯薬学研究部(医学域), 教授 (20263824)
Co-Investigator(Kenkyū-buntansha)	曽我部正博名古屋大学, 医学系研究科, 研究員 (10093428) 東谷篤志東北大学, 生命科学研究科, 教授 (40212162) 小林剛名古屋大学, 医学系研究科, 講師 (40402565) 平坂勝也長崎大学, 海洋未来イノベーション機構, 准教授 (70432747)
Project Period (FY)	2019-04-01 – 2022-03-31
Keywords	ロコモティブシンドローム / 筋萎縮 / ミトコンドリア / MAM / アコニターゼ / 抗酸化栄養素
Outline of Final Research Achievements	In this study, we investigated the effect of oxidative stress on aconitase activity. Clinorotation inhibited aconitase activity and enhanced the ubiquitin-proteasome system proteolytic pathway. N-Acetylcysteine (NAC) treatment restored this inhibited aconitase activity and suppressed the ubiquitin-proteasome-based proteolytic pathway. In addition, NAC treatment suppressed mitochondrial division, which is increased by clinorotation. Next, mice subjected to tail suspension for 2 weeks were allowed to drink 0.3% NAC solution, and the effect of suppressing muscle atrophy was examined. The hind limb muscles of the mice that drank the NAC solution had significantly suppressed muscle atrophy as compared with the group that drank the water. In addition, the aconitase activity in the muscle was also restored by NAC administration. Based on these results, it was considered that aconitase in the TCA cycle is likely to be a target enzyme for oxidative stress induced by disuse muscle atrophy.
Free Research Field	栄養生理学
Academic Significance and Societal Importance of the Research Achievements	ロコモティブ症候群とメタボリック症候群をオルガネラ連関の観点からとらえた研究は、本研究が初めてであった。本研究により、“不活動による筋萎縮も高血糖による筋萎縮もミトコンドリアと小胞体のオルガネラ連関(MAM構造)の破綻に起因したミトコンドリア代謝異常、とくにMAM構造の破綻から生じる酸化ストレスによるアコニターゼの活性低下である”という新しい概念を提唱できた。その成果は、機械的ストレスやエネルギー代謝異常の感知機構(メカノセンサーやエネルギーセンサー)の解明にとどまらず、抗酸化栄養素の持続的な投与による筋萎縮の治療に合目的な証拠を与えることができた。