Essential Amino Acid-Enriched Diet Alleviates Dexamethasone-Induced Loss of Muscle Mass and Function through Stimulation of Myofibrillar Protein Synthesis and Improves Glucose Metabolism in Mice

Metabolites

Jiyeon Jung¹  Yeongmin Kim¹  Jinseok Lee¹  Sanghee Park²  Jin-Ho Koh²  Il-Young Kim²  Cheol Soo Choi²  Jiwoong Jang³  Robert R. Wolfe⁴ 

[1] Department of Health Sciences and Technology, GAIHST, Gachon University, Incheon 21999, Korea;Department of Molecular Medicine, College of Medicine, Gachon University, Incheon 21999, Korea;Korea Mouse Metabolic Phenotyping Center, Lee Gil Ya Cancer and Diabetes Institute, Gachon University, Incheon 21999, Korea;The Center for Translational Research in Aging and Longevity, Department of Geriatrics, Donald W. Reynolds Institute on Aging, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA;

关键词: dexamethasone;    muscle atrophy;    essential amino acids;    protein turnover;    glucose metabolic flux;   

DOI  :  10.3390/metabo12010084

来源: DOAJ

【 摘 要 】

Dexamethasone (DEX) induces dysregulation of protein turnover, leading to muscle atrophy and impairment of glucose metabolism. Positive protein balance, i.e., rate of protein synthesis exceeding rate of protein degradation, can be induced by dietary essential amino acids (EAAs). In this study, we investigated the roles of an EAA-enriched diet in the regulation of muscle proteostasis and its impact on glucose metabolism in the DEX-induced muscle atrophy model. Mice were fed normal chow or EAA-enriched chow and were given daily injections of DEX over 10 days. We determined muscle mass and functions using treadmill running and ladder climbing exercises, protein kinetics using the D₂O labeling method, molecular signaling using immunoblot analysis, and glucose metabolism using a U-¹³C₆ glucose tracer during oral glucose tolerance test (OGTT). The EAA-enriched diet increased muscle mass, strength, and myofibrillar protein synthesis rate, concurrent with improved glucose metabolism (i.e., reduced plasma insulin concentrations and increased insulin sensitivity) during the OGTT. The U-¹³C₆ glucose tracing revealed that the EAA-enriched diet increased glucose uptake and subsequent glycolytic flux. In sum, our results demonstrate a vital role for the EAA-enriched diet in alleviating the DEX-induced muscle atrophy through stimulation of myofibrillar proteins synthesis, which was associated with improved glucose metabolism.

【 授权许可】

Unknown