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장지웅Jiwoong Jang

가천대학교

J. Cachexia Sarcopenia Muscle, Jun 16 2024, | https://doi.org/10.1002/jcsm.13519 Free essential amino acid feeding improves endurance during resistance training via DRP1-dependent mitochondrial remodelling

Jiwoong Jang ^1,2,3, Yeongmin Kim ^1,4, Taejeong Song ⁵, Sanghee Park ^1,6, Hee-Joo Kim^1,4, Jin-ho Koh ^1,6, Yoonil Cho ^2,4, Shi-Young Park ^2,7, Sakthivel Sadayappan ⁵, Hyo-Bum Kwak^8,9,10, Robert R. Wolfe¹¹, Il-Young Kim^{1,2,6 *} &Cheol Soo Choi ^{2,3,6 *}

¹Integrative Metabolic Fluxomics Lab, Lee Gil Ya Cancer and Diabetes Institute, Gachon University, Incheon, Korea;

²Korea Mouse Metabolic Phenotyping Center, Lee Gil YaCancer and Diabetes Institute, Gachon University, Incheon, Korea;

³Department of Internal Medicine, Gil Medical Center, Gachon University, Incheon, Korea;

⁴Department ofHealth Sciences and Technology, GAIHST, Gachon University, Incheon, Korea;

5Department of Internal Medicine, Division of Cardiovascular Health and Disease, Center for Cardiovascular Research, University of Cincinnati, Cincinnati, Ohio, USA;

⁶Department of Molecular Medicine, College of Medicine, Gachon University, Incheon, Korea;

⁷Gachon Biomedical Convergence Institute, Gachon University Gil Medical Center, Incheon, Korea;

⁸Department of Kinesiology, Inha University, Incheon, Korea;

⁹Institute of Sports & Arts Convergence, Inha University, Incheon, Korea;

¹⁰Department of Biomedical Science, Program in Biomedical Science & Engineering, Inha University, Incheon,Korea;

¹¹Department of Geriatrics, Center for Translational Research in Aging and Longevity, Donald W. Reynolds Institute on Aging, University of Arkansas for MedicalSciences, Little Rock, Arkansas, USA

^*Correspondence to: Il-Young Kim, Cheol Soo Choi

Abstract

Background: Loss of muscle strength and endurance with aging or in various conditions negatively affects quality of life. Resistance exercise training (RET) is the most powerful means to improve muscle mass and strength, but it does not generally lead to improvements in endurance capacity. Free essential amino acids (EAAs) act as precursors and stimuli for synthesis of both mitochondrial and myofibrillar proteins that could potentially confer endurance and strength gains. Thus, we hypothesized that daily consumption of a dietary supplement of nine free EAAs with RET improves endurance in addition to the strength gains by RET.

Methods: Male C57BL6J mice (9 weeks old) were assigned to control (CON), EAA, RET (ladder climbing, 3 times a week), or combined treatment of EAA and RET (EAA + RET) groups. Physical functions focusing on strength or endurance were assessed before and after the interventions. Several analyses were performed to gain better insight into the mechanisms by which muscle function was improved. We determined cumulative rates of myofibrillar and mitochondrial protein synthesis using 2H2O labelling and mass spectrometry; assessed ex vivo contractile properties and in vitro mitochondrial function, evaluated neuromuscular junction (NMJ) stability, and assessed implicated molecular singling pathways. Furthermore, whole-body and muscle insulin sensitivity along with glucose metabolism, were evaluated using a hyperinsulinaemic-euglycaemic clamp.

Results: EAA + RET increased muscle mass (10%, P < 0.05) and strength (6%, P < 0.05) more than RET alone, due to an enhanced rate of integrated muscle protein synthesis (19%, P < 0.05) with concomitant activation of Akt1/mTORC1 signalling. Muscle quality (muscle strength normalized to mass) was improved by RET (i.e., RET and EAA + RET) compared with sedentary groups (10%, P < 0.05), which was associated with increased AchR cluster size and MuSK activation (P < 0.05). EAA + RET also increased endurance capacity more than RET alone (26%, P < 0.05) by increasing both mitochondrial protein synthesis (53%, P < 0.05) and DRP1 activation (P < 0.05). Maximal respiratory capacity increased (P < 0.05) through activation of the mTORC1-DRP1 signalling axis. These favourable effects were accompanied by an improvement in basal glucose metabolism (i.e., blood glucose concentrations and endogenous glucose production vs. CON, P < 0.05).

Conclusions: Combined treatment with balanced free EAAs and RET may effectively promote endurance capacity as well as muscle strength through increased muscle protein synthesis, improved NMJ stability, and enhanced mitochondrial dynamics via mTORC1-DRP1 axis activation, ultimately leading to improved basal glucose metabolism.

논문정보

형식Research article
게재일2024년 06월 (BRIC 등록일 2024-06-18)
연구진국내(교신)+국외 연구진
분야 의약학 > 분자세포의학

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