Analytes and Metabolites Associated with Muscle Quality in Young, Healthy Adults

Identification of mechanisms that underlie lower extremity muscle quality (leg press one repetition maximum/total lean mass; LP/Lean) may be important for individuals interested in optimizing fitness and sport performance. The purpose of the current study was to provide observational insight into mechanisms that may underlie muscle quality by characterizing the association between 286 mass spectrometry metabolites and 17 chemistry screen analytes with LP/Lean in young, healthy adults (N = 77 (49 women and 28 men); mean age, 24.4 ± 4.2 yr; BMI, 23.5 ± 2.6 kg·m).

Principal components analysis (PCA) was used to reduce the 286 metabolites into 73 metabolite-containing PCA factors. Sex-adjusted linear regression was used to examine the association between PCA factors and chemistry screen analytes with LP/Lean. Q values were computed to account for multiple comparison testing. Stepwise linear regression and leave-one-out cross validation were used to identify a predictor set representative of LP/Lean and to assess internal validity, respectively.

Metabolites or analytes related to dietary protein intake (albumin, branched-chain amino acids (BCAA)) and excitation-contraction coupling (calcium and magnesium) were positively associated, whereas metabolites related to gut bacterial metabolism (cinnamoylglycine, hydrocinnamate, hippurate, indolepropionate) and peroxisome proliferator-activated receptor-alpha (PPAR-α) (methylglutarylcarnitine and cinnamoylglycine) activation were negatively associated with LP/Lean. Use of leave-one-out cross validation identified magnesium, sex, and the PCA factors containing BCAAs and methionine and methylglutarylcarnitine to be present in more than 90% of the stepwise regression models, thereby explaining 26.7% of the variance (adjusted R) inherent in muscle quality.

Collectively, these data suggest that mechanisms related to dietary protein intake, excitation-contraction coupling, gut microbial metabolism, and PPAR-α activation may underlie lower extremity muscle quality in young, healthy adults.