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An NMR-Based Approach to Identify Urinary Metabolites Associated with Acute Physical Exercise and Cardiorespiratory Fitness in Healthy Humans-Results of the KarMeN Study.

ABSTRACT: Knowledge on metabolites distinguishing the metabolic response to acute physical exercise between fit and less fit individuals could clarify mechanisms and metabolic pathways contributing to the beneficial adaptations to exercise. By analyzing data from the cross-sectional KarMeN (Karlsruhe Metabolomics and Nutrition) study, we characterized the acute effects of a standardized exercise tolerance test on urinary metabolites of 255 healthy women and men. In a second step, we aimed to detect a urinary metabolite pattern associated with the cardiorespiratory fitness (CRF), which was determined by measuring the peak oxygen uptake (VO2peak) during incremental exercise. Spot urine samples were collected pre- and post-exercise and 47 urinary metabolites were identified by nuclear magnetic resonance (NMR) spectroscopy. While the univariate analysis of pre-to-post-exercise differences revealed significant alterations in 37 urinary metabolites, principal component analysis (PCA) did not show a clear separation of the pre- and post-exercise urine samples. Moreover, both bivariate correlation and multiple linear regression analyses revealed only weak relationships between the VO2peak and single urinary metabolites or urinary metabolic pattern, when adjusting for covariates like age, sex, menopausal status, and lean body mass (LBM). Taken as a whole, our results show that several urinary metabolites (e.g., lactate, pyruvate, alanine, and acetate) reflect acute exercise-induced alterations in the human metabolism. However, as neither pre- and post-exercise levels nor the fold changes of urinary metabolites substantially accounted for the variation of the covariate-adjusted VO2peak, our results furthermore indicate that the urinary metabolites identified in this study do not allow to draw conclusions on the individual's physical fitness status. Studies investigating the relationship between the human metabolome and functional variables like the CRF should adjust for confounders like age, sex, menopausal status, and LBM.

SUBMITTER: Kistner S

PROVIDER: S-EPMC7281079 | biostudies-literature | 2020 May

REPOSITORIES: biostudies-literature

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An NMR-Based Approach to Identify Urinary Metabolites Associated with Acute Physical Exercise and Cardiorespiratory Fitness in Healthy Humans-Results of the KarMeN Study.

Kistner Sina S Rist Manuela J MJ Döring Maik M Dörr Claudia C Neumann Rainer R Härtel Sascha S Bub Achim A

Metabolites 20200521 5

Knowledge on metabolites distinguishing the metabolic response to acute physical exercise between fit and less fit individuals could clarify mechanisms and metabolic pathways contributing to the beneficial adaptations to exercise. By analyzing data from the cross-sectional KarMeN (Karlsruhe Metabolomics and Nutrition) study, we characterized the acute effects of a standardized exercise tolerance test on urinary metabolites of 255 healthy women and men. In a second step, we aimed to detect a urin ...[more]

PMID: 32455749

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Project description:Cardiorespiratory fitness (CRF) represents a strong predictor of all-cause mortality and is strongly influenced by regular physical activity (PA). However, the biological mechanisms involved in the body's adaptation to PA remain to be fully elucidated. The aim of this study was to systematically examine the relationship between CRF and plasma metabolite patterns in 252 healthy adults from the cross-sectional Karlsruhe Metabolomics and Nutrition (KarMeN) study. CRF was determined by measuring the peak oxygen uptake during incremental exercise. Fasting plasma samples were analyzed by nuclear magnetic resonance spectroscopy and mass spectrometry coupled to one- or two-dimensional gas chromatography or liquid chromatography. Based on this multi-platform metabolomics approach, 427 plasma analytes were detected. Bi- and multivariate association analyses, adjusted for age and menopausal status, showed that CRF was linked to specific sets of metabolites primarily indicative of lipid metabolism. However, CRF-related metabolite patterns largely differed between sexes. While several phosphatidylcholines were linked to CRF in females, single lyso-phosphatidylcholines and sphingomyelins were associated with CRF in males. When controlling for further assessed clinical and phenotypical parameters, sex-specific CRF tended to be correlated with a smaller number of metabolites linked to lipid, amino acid, or xenobiotics-related metabolism. Interestingly, sex-specific CRF explanation models could be improved when including selected plasma analytes in addition to clinical and phenotypical variables. In summary, this study revealed sex-related differences in CRF-associated plasma metabolite patterns and proved known associations between CRF and risk factors for cardiometabolic diseases such as fat mass, visceral adipose tissue mass, or blood triglycerides in metabolically healthy individuals. Our findings indicate that covariates like sex and, especially, body composition have to be considered when studying blood metabolic markers related to CRF.

Project description:Background Considerable attention has been paid to interindividual differences in the cardiorespiratory fitness (CRF) response to exercise. However, the complex multifactorial nature of CRF response variability poses a significant challenge to our understanding of this issue. We aimed to explore whether unsupervised clustering can take advantage of large amounts of clinical data and identify latent subgroups with different CRF exercise responses within a healthy population. Methods 252 healthy participants (99 men, 153 women; 36.8 ± 13.4 yr) completed moderate endurance training on 3 days/week for 4 months, with exercise intensity prescribed based on anaerobic threshold (AT). Detailed clinical measures, including resting vital signs, ECG, cardiorespiratory parameters, echocardiography, heart rate variability, spirometry and laboratory data, were obtained before and after the exercise intervention. Baseline phenotypic variables that were significantly correlated with CRF exercise response were identified and subjected to selection steps, leaving 10 minimally redundant variables, including age, BMI, maximal oxygen uptake (VO2max), maximal heart rate, VO2 at AT as a percentage of VO2max, minute ventilation at AT, interventricular septal thickness of end-systole, E velocity, root mean square of heart rate variability, and hematocrit. Agglomerative hierarchical clustering was performed on these variables to detect latent subgroups that may be associated with different CRF exercise responses. Results Unsupervised clustering revealed two mutually exclusive groups with distinct baseline phenotypes and CRF exercise responses. The two groups differed markedly in baseline characteristics, initial fitness, echocardiographic measurements, laboratory values, and heart rate variability parameters. A significant improvement in CRF following the 16-week endurance training, expressed by the absolute change in VO2max, was observed only in one of the two groups (3.42 ± 0.4 vs 0.58 ± 0.65 ml⋅kg−1∙min−1, P = 0.002). Assuming a minimal clinically important difference of 3.5 ml⋅kg−1∙min−1 in VO2max, the proportion of population response was 56.1% and 13.9% for group 1 and group 2, respectively (P<0.001). Although group 1 exhibited no significant improvement in CRF at group level, a significant decrease in diastolic blood pressure (70.4 ± 7.8 vs 68.7 ± 7.2 mm Hg, P = 0.027) was observed. Conclusions Unsupervised learning based on dense phenotypic characteristics identified meaningful subgroups within a healthy population with different CRF responses following standardized aerobic training. Our model could serve as a useful tool for clinicians to develop personalized exercise prescriptions and optimize training effects.

Project description:Physical exercise (PE) has been shown to improve brain function via multiple neurobiological mechanisms promoting neuroplasticity. Cognitive exercise (CE) combined with PE may show an even greater effect on cognitive function. Brain-derived neurotrophic factor (BDNF) is important for neuroplastic signaling, may reduce with increasing age, and is confounded by fitness. The source and physiological role of human peripheral blood BDNF in plasma (pBDNF) is thought to differ from that in serum (sBDNF), and it is not yet known how pBDNF and sBDNF respond to PE and CE. A training intervention study in healthy older adults investigated the effects of acute (35 min) and prolonged (12 weeks, 30 sessions) CE and PE, both alone and in combination, on pBDNF and sBDNF. Cross-sectional associations between baseline pBDNF, sBDNF and cardiorespiratory fitness (CRF) were also investigated. Participants (65-75 years) were randomly assigned to four groups and prescribed either CE plus 35 min of rest (n = 21, 52% female); PE [performed on a cycle ergometer at moderate intensity (65-75% of individual maximal heart rate)] plus 35 min of rest (n = 27, 56% female); CE plus PE (n = 24, 46% female), or PE plus CE (n = 25, 52% female). Groups were tested for CRF using a maximal treadmill ergometer test (VO2peak); BDNF levels (collected 48 h after CRF) during baseline, after first exercise (PE or CE) and after second exercise (PE, CE or rest); and cognitive ability pre and post 12-week training. At both pre and post, pBDNF increased after CE and PE (up to 222%), and rest (∼67%), whereas sBDNF increased only after PE (up to 18%) and returned to baseline after rest. Acute but not prolonged PE increased both pBDNF and sBDNF. CE induced acute changes in pBDNF only. Baseline pBDNF was positively associated with baseline sBDNF (n = 93, r = 0.407, p < 0.001). No changes in CRF were found in any of the groups. Baseline CRF did not correlate with baseline BDNF. Even though baseline pBDNF and sBDNF were associated, patterns of changes in pBDNF and sBDNF in response to exercise were explicitly different. Further experimental scrutiny is needed to clarify the biological mechanisms of these results.

Dataset Information

An NMR-Based Approach to Identify Urinary Metabolites Associated with Acute Physical Exercise and Cardiorespiratory Fitness in Healthy Humans-Results of the KarMeN Study.

Publications

An NMR-Based Approach to Identify Urinary Metabolites Associated with Acute Physical Exercise and Cardiorespiratory Fitness in Healthy Humans-Results of the KarMeN Study.

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