Serum Branched-chain Amino Acid Metabolites Increase When Aerobic Exercise Is Initiated With Low Muscle Glycogen

Abstract

PURPOSE: Initiating aerobic exercise with low muscle glycogen blunts anabolic signaling and myogenesis. The underlying mechanisms causing the reduction in post-exercise anabolic signaling is unclear. This study aimed to identify metabolic factors that might contribute to the apparent muscle anabolic resistance that occurs when aerobic exercise is initiated with low muscle glycogen using global metabolomics. METHODS: Using a randomized, crossover design, 11 men (mean ± SD, age: 21 ± 4 y; VO2peak: 44 ± 4 mL/kg/min) completed 2 cycle ergometry glycogen depletion trials, followed by 24 hours of isocaloric high fat (1.5 g/kg carbohydrate, 3.0 g/kg fat) or high carbohydrate (6.0 g/kg carbohydrate, 1.0 g/kg fat) refeeding to elicit low (LOW; 217 ± 103 mmol/kg dry wt) or adequate (AD; 396 ± 70 mmol/kg dry wt) muscle glycogen content. Participants then performed 80 min of cycle ergometry (64 ± 3% VO2peak) and ingested 146 g of carbohydrate. Serum samples for metabolomics analysis were collected before glycogen depletion under resting, fasted conditions (BASELINE), before (PRE) and immediately after (POST) exercise. Changes in metabolite profiles were calculated by subtracting BASELINE from PRE and POST within LOW and AD. RESULTS: Treatment or time-by-treatment interactions were observed in 309 metabolites (P < 0.05, Q < 0.10), with 78% of identified metabolites being related amino acid or fatty acid metabolism. There were greater decreases in 80% of diacylglycerol metabolites, while 69% of acyl-carnitine metabolites had greater increases in LOW compared to AD (P < 0.05, Q < 0.10). There were greater increases in 64% of branched-chain amino acids (BCAA) metabolites, as well as urea and 3-methylhistidine in LOW compared to AD (P < 0.05, Q < 0.10). CONCLUSION: Greater increases in BCAA and acyl-carnitine metabolites, as well as urea and 3-methylhistidine, suggest that when aerobic exercise is initiated low muscle glycogen, the reliance on BCAA catabolism for substrate oxidation is greater than when exercise is initiated with adequate glycogen stores. Findings may provide a metabolic explanation for why muscle is anabolically resistant to the mechanical stimulus of exercise, and suggest exogenous BCAA requirements to optimize muscle recovery are likely increased when glycogen stores are limited.