Serum Branched-Chain Amino Acid Metabolites Increase in Males When Aerobic Exercise Is Initiated with Low Muscle Glycogen

Lee M Margolis,Claire C Whitney,Stefan M Pasiakos,Julie L Coleman,J Philip Karl,Marques A Wilson

doi:10.3390/metabo11120828

Abstract

This study used global metabolomics to identify metabolic factors that might contribute to muscle anabolic resistance, which develops when aerobic exercise is initiated with low muscle glycogen using global metabolomics. Eleven men completed this randomized, crossover study, completing two cycle ergometry glycogen depletion trials, followed by 24 h of isocaloric refeeding to elicit low (LOW; 1.5 g/kg carbohydrate, 3.0 g/kg fat) or adequate (AD; 6.0 g/kg carbohydrate 1.0 g/kg fat) glycogen. Participants then performed 80 min of cycling (64 ± 3% VO2 peak) while ingesting 146 g carbohydrate. Serum was collected before glycogen depletion under resting and fasted conditions (BASELINE), and before (PRE) and after (POST) exercise. Changes in metabolite profiles were calculated by subtracting BASELINE from PRE and POST within LOW and AD. There were greater increases (p < 0.05, Q < 0.10) in 64% of branched-chain amino acids (BCAA) metabolites and 69% of acyl-carnitine metabolites in LOW compared to AD. Urea and 3-methylhistidine had greater increases (p < 0.05, Q < 0.10) in LOW compared to AD. Changes in metabolomics profiles indicate a greater reliance on BCAA catabolism for substrate oxidation when exercise is initiated with low glycogen stores. These findings provide a mechanistic explanation for anabolic resistance associated with low muscle glycogen, and suggest that exogenous BCAA requirements to optimize muscle recovery are likely greater than current recommendations.

Highlights

Performing aerobic exercise with low muscle glycogen stores has become popular over recent years [1,2,3,4]
The main finding from this study was that initiating aerobic exercise with low glycogen concentrations alters global metabolomics profiles before and after exercise compared to when exercise is initiated with adequate glycogen
Greater increases in branched-chain amino acids (BCAA) and acyl-carnitine metabolites, and urea and 3-methylhistidine, indicate there is an increased reliance on BCAA catabolism for substrate oxidation when aerobic exercise is initiated in LOW compared to AD muscle glycogen

Summary

Introduction

Performing aerobic exercise with low muscle glycogen stores has become popular over recent years [1,2,3,4]. Performing aerobic exercise with low glycogen stores may compromise muscle repair and recovery [10,11] since the low muscle glycogen levels appear to increase the reliance on endogenous protein oxidation to meet metabolic demands [10,12], branched-chain amino acids (BCAA). This results in lower rates of muscle protein synthesis [10,11] and blunts activation of the mechanistic target of rapamycin complex 1 (mTORC1) signaling pathway [13,14]. While these data indicate a potential reduction in the anabolic response to aerobic exercise when muscle glycogen content is low, the specific mechanism suppressing the anabolic state is unclear

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