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Article

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

1
Department of Physiology and Biochemistry of Nutrition, Max Rubner-Institut, 76131 Karlsruhe, Germany
2
Department of Safety and Quality of Fruit and Vegetables, Max Rubner-Institut, 76131 Karlsruhe, Germany
3
Institute of Sports and Sports Science, Karlsruhe Institute of Technology, 76131 Karlsruhe, Germany
*
Author to whom correspondence should be addressed.
Present address: German National Reference Centre for Authentic Food, Max Rubner-Institut, 95326 Kulmbach, Germany.
Present address: Pantherna Therapeutics GmbH, 16761 Hennigsdorf, Germany.
§
Present address: Institute of Movement and Sport, Karlsruhe University of Education, 76133 Karlsruhe, Germany.
Present address: TSG 1899 Hoffenheim, 74939 Zuzenhausen, Germany.
Academic Editor: Vassilis Mougios
Metabolites 2021, 11(7), 463; https://doi.org/10.3390/metabo11070463
Received: 22 June 2021 / Revised: 9 July 2021 / Accepted: 15 July 2021 / Published: 17 July 2021
(This article belongs to the Special Issue Effect of Exercise on Energy Metabolism)
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. View Full-Text
Keywords: cardiorespiratory fitness; physical fitness; metabolomics; plasma metabolome; plasma metabolite patterns; metabolite profiles cardiorespiratory fitness; physical fitness; metabolomics; plasma metabolome; plasma metabolite patterns; metabolite profiles
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MDPI and ACS Style

Kistner, S.; Döring, M.; Krüger, R.; Rist, M.J.; Weinert, C.H.; Bunzel, D.; Merz, B.; Radloff, K.; Neumann, R.; Härtel, S.; Bub, A. Sex-Specific Relationship between the Cardiorespiratory Fitness and Plasma Metabolite Patterns in Healthy Humans—Results of the KarMeN Study. Metabolites 2021, 11, 463. https://doi.org/10.3390/metabo11070463

AMA Style

Kistner S, Döring M, Krüger R, Rist MJ, Weinert CH, Bunzel D, Merz B, Radloff K, Neumann R, Härtel S, Bub A. Sex-Specific Relationship between the Cardiorespiratory Fitness and Plasma Metabolite Patterns in Healthy Humans—Results of the KarMeN Study. Metabolites. 2021; 11(7):463. https://doi.org/10.3390/metabo11070463

Chicago/Turabian Style

Kistner, Sina, Maik Döring, Ralf Krüger, Manuela J. Rist, Christoph H. Weinert, Diana Bunzel, Benedikt Merz, Katrin Radloff, Rainer Neumann, Sascha Härtel, and Achim Bub. 2021. "Sex-Specific Relationship between the Cardiorespiratory Fitness and Plasma Metabolite Patterns in Healthy Humans—Results of the KarMeN Study" Metabolites 11, no. 7: 463. https://doi.org/10.3390/metabo11070463

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