Bork Julia, Markus Marcello R P, Ewert Ralf, Nauck Matthias, Templin Christian, Völzke Henry, Kastenmüller Gabi, Artati Anna, Adamski Jerzy, Dörr Marcus, Friedrich Nele, Bahls Martin
Department of Internal Medicine B, University Medicine Greifswald, Greifswald, Germany.
German Centre for Cardiovascular Research (DZHK), Partner Site Greifswald, Greifswald, Germany.
Scand J Med Sci Sports. 2025 Mar;35(3):e70034. doi: 10.1111/sms.70034.
High cardiorespiratory fitness (CRF) is associated with better overall health. This study aimed to find a metabolic signature associated with CRF to identify health-promoting effects. CRF based on cardiopulmonary exercise testing, targeted and untargeted metabolomics approaches based on mass spectrometry, and clinical data from two independent cohorts of the Study of Health in Pomerania (SHIP) were used. Sex-stratified linear regression models were adjusted for age, smoking, and height to relate CRF with individual metabolites. A total of 132 (SHIP-START-2: 483 men with a median age of 58 years and 450 women with a median age of 56 years) and 118 (SHIP-TREND-0: 341 men and 371 women both with a median age of 51 years) metabolites were associated with CRF. Lipids showed bidirectional relations to CRF independent of sex. Specific subsets of sphingomyelins were positively related to CRF in men (SM (OH) C14:1, SM(OH)C22:2 SM C16:0, SM C20:2 SM(OH)C24:1) and inversely in women (SM C16:1, SM C18:0, SM C18:1). Metabolites involved in energy production (citrate and succinylcarnitine) were only associated with CRF in men. In women, xenobiotics (hippurate, stachydrine) were related to CRF. The sex-specific metabolic signature of CRF is influenced by sphingomyelins, energy substrates, and xenobiotics. The greater effect estimates seen in women may emphasize the important role of CRF in maintaining metabolic health. Future research should explore how this profile changes with different types of exercise interventions or diseases in diverse populations and how these metabolites could be implemented in primary prevention settings.
高心肺适能（CRF）与更好的整体健康状况相关。本研究旨在寻找与CRF相关的代谢特征，以确定其对健康的促进作用。研究采用了基于心肺运动测试的CRF、基于质谱的靶向和非靶向代谢组学方法，以及来自波美拉尼亚健康研究（SHIP）两个独立队列的临床数据。通过性别分层的线性回归模型，对年龄、吸烟和身高进行了调整，以关联CRF与个体代谢物。共有132种（SHIP-START-2：483名男性，中位年龄58岁；450名女性，中位年龄56岁）和118种（SHIP-TREND-0：341名男性和371名女性，中位年龄均为51岁）代谢物与CRF相关。脂质与CRF呈现双向关系，且不受性别的影响。鞘磷脂的特定亚组在男性中与CRF呈正相关（SM(OH)C14:1、SM(OH)C22:2、SM C16:0、SM C20:2、SM(OH)C24:1），而在女性中呈负相关（SM C16:1、SM C18:0、SM C18:1）。参与能量产生的代谢物（柠檬酸和琥珀酰肉碱）仅在男性中与CRF相关。在女性中，外源性物质（马尿酸盐、水苏碱）与CRF相关。CRF的性别特异性代谢特征受鞘磷脂、能量底物和外源性物质的影响。在女性中观察到的更大效应估计值可能强调了CRF在维持代谢健康中的重要作用。未来的研究应探索这种特征在不同人群中如何随不同类型的运动干预或疾病而变化，以及这些代谢物如何应用于一级预防。
