Possible mechanism underlying exercise training-mediated the differentiation of adipose-derived stem cells: roles of intracellular amino acid metabolism

2022 Fiscal Year Final Research Report

• Project/Area Number: 19H04010
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Review Section: Basic Section 59020:Sports sciences-related
• Research Institution: Doshisha University
• Principal Investigator: Izawa Tetsuya 同志社大学, スポーツ健康科学部, 教授 (70147495)
• Co-Investigator(Kenkyū-buntansha): 小笠原 準悦 旭川医科大学, 医学部, 客員講師 (20415110) ; 加藤 久詞 独立行政法人国立病院機構(京都医療センター臨床研究センター), 内分泌代謝高血圧研究部, 研究員 (30780275)
• Project Period (FY): 2019-04-01 – 2023-03-31
• Keywords: 脂肪由来幹細胞 / adipogenesis / アミノ酸 / 運動トレーニング / 高脂肪食

Outline of Final Research Achievements

This study clarified the mechanism of exercise training (TR)-induced change in the differentiation ability of adipose-derived stem cells (ADSCs) to adipocytes by investigating amino acid-mediated signal transduction. TR inhibited adipogenic differentiation of ADSCs with reduced expression of PPARγ protein. TR also affected L-leucine-induced changes in the protein expression of Sestrin2 and mTORC1. However, these responses to TR differed between subcutaneous and visceral adipose tissue ADSCs. In particular, bioinformatics analysis revealed that the down-regulation of branched-chain amino acid degradation pathways was enriched in adipocytes differentiated from ADSCs derived from subcutaneous adipose tissue. The findings obtained in this study would be extremely significant in constructing new exercise therapy for obesity, focusing on the effects of amino acids.

Free Research Field

スポーツ生化学

Academic Significance and Societal Importance of the Research Achievements

脂肪組織の成熟脂肪細胞は一定の割合で細胞死を起こし，脂肪由来幹細胞が新しい脂肪細胞を補充することで，脂肪組織を構成する細胞の質や状態（cellularity）を維持する．そのため，脂肪由来幹細胞の分化機構に与える過栄養や運動の効果を明白にすることは，この分野の研究に大きなブレイクスルーをもたらす．本研究は，運動療法による脂肪由来幹細胞の脂肪分化能の制御機構はアミノ酸の修飾を受けている可能性を強く示唆し，肥満の運動療法の背景にある分子機構の解明を大きく前進させるものである．加えて，本研究はアミノ酸に着目した新しい運動療法の構築に重要な学術的知見を提供し，その社会的意義も大きい．