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

Abstract

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 ( 1 H 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.

Sex-Specific Relationship between the Cardiorespiratory Fitness and Plasma Metabolite Patterns in Healthy Humans—Results of the KarMeN Study

“…While the tricarboxylic acid (TCA) cycle intermediate citric acid only showed a relevant positive correlation with the VO 2peak in females, malic acid and succinic acid tended to be positively linked to CRF in both sexes. Previous studies revealed a rise in fasting plasma malic acid after weight loss and PE intervention in obese women [ 58 ], a training-induced increase in muscular succinic acid in subjects at risk of metabolic disease [ 52 ], or a slightly positive correlation between CRF and serum succinic acid in healthy young men [ 59 ]. Despite weak bivariate correlations, our results support the suggestion that specific TCA cycle intermediates might be potentially interesting blood markers of the beneficial effects of chronic PA occurring at a muscular level, such as an increased mitochondrial density or TCA cycle capacity.…”

“…Choline participates in multiple pathways of lipid or AA metabolism, serving as a precursor for PC species, the neurotransmitter acetylcholine, or betaine. Circulating choline can result from diet or PC breakdown [ 61 ] and was shown to be either lower [ 18 ] or higher [ 59 , 62 ] in fitter individuals. Even though a more efficient conversion of PCs to choline in trained individuals was assumed [ 62 ], it cannot be excluded that female KarMeN subjects with high CRF were also characterized by a higher dietary choline intake.…”

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

“…A total of eighty healthy and sedentary young Caucasian men, which seventy were defined as completers [age: 23.7 ± 3.0 yr; height: 1.74 ± 0.06 m; body mass: 75.2 ± 8.8; body fat: 20.0 ± 7.4%; body mass index (BMI): 24.8 ± 2.5 kg·m −2 ], from the TIMES study, were used for analysis (Castro A., et al, 2019 ). Briefly, participants were sedentary and did not engage in regular exercise defined as 30 min.wk −1 at an energy expenditure of 6 METS or more in the previous 4 months (Riebe et al, 2018 ; Castro A., et al, 2019 ; Castro et al, 2021 ). All participants were free from diabetes (fasting glucose > 7.0 mmol·L−1), hypertension (blood pressure > 140/90 mmHg), dyslipidemia (based on medication use), severe obesity (defined as body mass index > 33 kg·m −2 ), smoking, metabolic disorders, heart diseases, musculoskeletal problems interfering with exercise or significant chronic respiratory conditions (Castro A., et al, 2019 ).…”

“…MPO was estimated as W+[25·( t /60)], where W is the last load reached and t is the number of seconds in the test's final load (Kuipers et al, 1985 ). The highest MPO value recorded between tests was considered for the analyses and defined as the measure of CRF (Castro A., et al, 2019 ; Castro et al, 2021 ). The within-test coefficient of variations (CV) and intraclass correlation coefficient (ICC) were 2.8% and 0.98, respectively.…”

“…Particularly, metabolomics is a powerful metabolic phenotyping technology that allows to identify and quantify metabolites that reflect the biochemical activity underlying different physiological conditions and complex phenotypes (Rinschen et al, 2019 ; Wishart, 2019a ), such as CRF (Castro A., et al, 2019 ; Castro et al, 2021 ). In this sense, nuclear magnetic resonance (NMR) spectroscopy is known for its reproducibility, nondestructive nature and minimal sample preparation (Wishart, 2019b ), being one of the most widely employed metabolomics platforms for detecting and quantifying metabolites and their metabolic pathways related to exercise, physical activity, and health (Duft et al, 2017b ; Kelly et al, 2020 ).…”