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

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.

SUBMITTER: Margolis LM

PROVIDER: S-EPMC8708125 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BackgroundCirculating branched-chain amino acids (BCAAs-isoleucine, leucine, and valine) are strongly associated with higher risk of incident type 2 diabetes (T2D); however, determinants of elevated fasting BCAA concentrations are largely unknown.ObjectivesWe aimed to characterize the modifiable lifestyle factors related to plasma BCAAs.MethodsWe performed a cross-sectional analysis among n = 18,897 women (mean ± SD age: 54.9 ± 7.2 y) in the Women's Health Study, free of T2D and cardiovascular disease at baseline blood draw. Lifestyle factors, weight, and height were self-reported via questionnaire, including smoking status, alcohol, leisure-time physical activity (LTPA), diet quality scores [2010 Alternative Healthy Eating Index (without alcohol) (aHEI); alternate Mediterranean Diet (aMED)], and dietary sources of BCAAs. Plasma BCAAs were quantified via NMR spectroscopy. We calculated multivariable-adjusted percentage mean differences (95% CIs) and P values for linear trend of BCAAs stratified by categoric lifestyle factors. We estimated R2 from univariate cubic spline regression models to estimate the variability in BCAAs explained.ResultsCompared with women with BMI (in kg/m2) <25.0, BCAAs were 8.6% (95% CI: 8.0%, 9.3%), 15.3% (95% CI: 14.4%, 16.3%), and 21.0% (95% CI: 18.2%, 23.9%) higher for the BMI strata 25.0-29.9, 30.0-39.9, and ≥40.0, respectively (P-trend < 0.0001). Women with higher LTPA and higher alcohol intake compared with lower had modestly (∼1%) lower plasma BCAAs (P-trend = 0.014 and 0.0003, respectively). Differences in smoking status, aHEI, and aMED score were not related to plasma BCAAs. Women with higher dietary BCAAs had dose-response higher plasma BCAA concentrations, 3.4% (95% CI: 2.5%, 4.4%) higher when comparing the highest with the lowest quintile (P-trend < 0.0001). BMI explained 11.6% of the variability of BCAAs, whereas other factors explained between 0.1% and 1%.ConclusionsOur findings among a large cohort of US women indicate that BMI, but less so diet, physical activity, and other lifestyle factors, is related to plasma BCAAs.This trial was registered at clinicaltrials.gov as NCT00000479.

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

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