Association Between Changes in Serum and Skeletal Muscle Metabolomics Profile With Maximum Power Output Gains in Response to Different Aerobic Training Programs: The Times Study.

Purpose: High heterogeneity of the response of cardiorespiratory fitness (CRF) to standardized exercise doses has been reported in different training programs, but the associated mechanisms are not widely known. This study investigated whether changes in the metabolic profile and pathways in blood serum and the skeletal muscle are associated with the inter-individual variability of CRF responses to 8-wk of continuous endurance training (ET) or high-intensity interval training (HIIT). Methods: Eighty men, young and sedentary, were randomized into three groups, of which 70 completed 8 wk of intervention (> 90% of sessions): ET, HIIT, or control. Blood and vastus lateralis muscle tissue samples, as well as the measurement of CRF [maximal power output (MPO)] were obtained before and after the intervention. Blood serum and skeletal muscle samples were analyzed by 600 MHz 1H-NMR spectroscopy (metabolomics). Associations between the pretraining to post-training changes in the metabolic profile and MPO gains were explored via three analytical approaches: (1) correlation between pretraining to post-training changes in metabolites' concentration levels and MPO gains; (2) significant differences between low and high MPO responders; and (3) metabolite contribution to significantly altered pathways related to MPO gains. After, metabolites within these three levels of evidence were analyzed by multiple stepwise linear regression. The significance level was set at 1%. Results: The metabolomics profile panel yielded 43 serum and 70 muscle metabolites. From the metabolites within the three levels of evidence (15 serum and 4 muscle metabolites for ET; 5 serum and 1 muscle metabolites for HIIT), the variance in MPO gains was explained: 77.4% by the intervention effects, 6.9, 2.3, 3.2, and 2.2% by changes in skeletal muscle pyruvate and valine, serum glutamine and creatine phosphate, respectively, in ET; and 80.9% by the intervention effects; 7.2, 2.2, and 1.2% by changes in skeletal muscle glycolate, serum creatine and creatine phosphate, respectively, in HIIT. The most changed and impacted pathways by these metabolites were: arginine and proline metabolism, glycine, serine and threonine metabolism, and glyoxylate and dicarboxylate metabolism for both ET and HIIT programs; and additional alanine, aspartate and glutamate metabolism, arginine biosynthesis, glycolysis/gluconeogenesis, and pyruvate metabolism for ET. Conclusion: These results suggest that regulating the metabolism of amino acids and carbohydrates may be a potential mechanism for understanding the inter-individual variability of CRF in responses to ET and HIIT programs.

Understanding the Relationship between Intrinsic Cardiorespiratory Fitness and Serum and Skeletal Muscle Metabolomics Profile.

Intrinsic cardiorespiratory fitness (iCRF) indicates the CRF level in the sedentary state. However, even among sedentary individuals, a wide interindividual variability is observed in the iCRF levels, whose associated molecular characteristics are little understood. This study aimed to investigate whether serum and skeletal muscle metabolomics profiles are associated with iCRF, measured by maximal power output (MPO). Seventy sedentary young adults were submitted to venous blood sampling, a biopsy of the vastus lateralis muscle and iCRF assessment. Blood serum and muscle tissue samples were analyzed by proton nuclear magnetic resonance (1H NMR) spectroscopy. Metabolites related to iCRF were those supported by three levels of evidence: (1) correlation with iCRF, (2) significant difference between individuals with low and high iCRF, and (3) metabolite contribution to significant pathways associated with iCRF. From 43 serum and 70 skeletal muscle analyzed metabolites, iCRF was positively associated with levels of betaine, threonine, proline, ornithine, and glutamine in serum and lactate, fumarate, NADP+, and formate in skeletal muscle. Serum betaine and ornithine and skeletal muscle lactate metabolites explained 31.2 and 16.8%, respectively, of the iCRF variability in addition to body mass. The results suggest that iCRF in young adults is positively associated with serum and skeletal muscle metabolic levels, indicative of the amino acid and carbohydrate metabolism.

Augmented Anabolic Responses after 8-wk Cycling with Blood Flow Restriction.

INTRODUCTION: Low-intensity endurance training (ET) performed with blood flow restriction (BFR) can improve muscle strength, cross-sectional area (CSA) and cardiorespiratory capacity. Whether muscle strength and CSA as well as cardiorespiratory capacity (i.e., V˙O2max) and underlying molecular processes regulating such respective muscle adaptations are comparable to resistance and ET is unknown. PURPOSE: To determine the respective chronic (i.e., 8 wk) functional, morphological, and molecular responses of ET-BFR training compared with conventional, unrestricted resistance training (RT) and ET. METHODS: Thirty healthy young men were randomly assigned to one of three experimental groups: ET-BFR (n = 10, 4 d·wk, 30-min cycling at 40% of V˙O2max), RT (n = 10, 4 d·wk, 4 sets of 10 repetitions leg press at 70% of one repetition maximum with 60 s rest) or ET (n = 10, 4 d·wk, 30-min cycling at 70% of V˙O2max) for 8 wk. Measures of quadriceps CSA, leg press one repetition maximum, and V˙O2max as well as muscle biopsies were obtained before and after intervention. RESULTS: Both RT and ET-BFR increased muscle strength and hypertrophy responses. ET-BFR also increased V˙O2max, total cytochrome c oxidase subunit 4 isoform 1 abundance and vascular endothelial growth factor mRNA abundance despite the lower work load compared to ET. CONCLUSIONS: Eight weeks of ET-BFR can increase muscle strength and induce similar muscle hypertrophy responses to RT while V˙O2max responses also increased postintervention even with a significantly lower work load compared with ET. Our findings provide new insight to some of the molecular mechanisms mediating adaptation responses with ET-BFR and the potential for this training protocol to improve muscle and cardiorespiratory capacity.