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.

Yeongmin Kim,Jiwoong Jang,Jin-Ho Koh,Il-Young Kim,Jiyeon Jung,Jinseok Lee,Robert R Wolfe,Cheol Soo Choi,Sanghee Park

doi:10.3390/metabo12010084

Abstract

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.

Highlights

Muscle atrophy is defined as the loss of muscle mass and function resulting from decreased protein synthesis and/or increased protein degradation [1,2]
We examined whether an essential amino acids (EAAs)-enriched diet can prevent the loss of muscle and function induced by DEX
We found that 20 mg/kg DEX daily injection for 10 days significantly decreased body weight in all groups (Figure 1A)

Summary

Introduction

Muscle atrophy is defined as the loss of muscle mass and function (including strength and endurance) resulting from decreased protein synthesis and/or increased protein degradation [1,2]. Despite its pharmacological benefits in disease conditions, acute and prolonged treatment with DEX induces an imbalance in protein turnover and impaired glucose metabolism, leading to a decrease in both muscle mass and function. DEX treatment decreases muscle weight and inhibits the mTOR pathway, reduces the rate of muscle protein synthesis by 59%, and reduces muscle strength by up to 50% [6,7]. It is important to examine whether alterations occur both in muscle protein turnover and metabolism to better understand and in turn treat the DEX-induced muscle atrophy. Previous studies have evaluated the effects of nutraceuticals, such as BCAA and omega-3 fatty acids, in vivo [17,18] without examinations on both protein turnover and metabolism

Methods

Results

Conclusion