Serum Metabolome And Cardiovascular Autonomic Modulation In Active And Sedentary Men

PURPOSE: To investigate the impact of regular physical activity on the serum metabolome and cardiovascular autonomic modulation (CAM), and the interrelationship between these components, in healthy men. METHODS: 51 healthy men (37 ± 10 years; 23.6 ± 2.4 kg/m2) were divided into 2 groups: sedentary [N = 17; physical exercise <150 min/week for at least 6 months] and active (N = 34; physical exercise ≥150 min/week for at least 6 months). Blood samples were collected after 12-hour fast and analyzed using hydrogen nuclear magnetic resonance (H1NMR) and liquid chromatography coupled with high-resolution mass spectrometry (LC-HRMS) to access the serum metabolome. Resting cardiovascular data was collected to assess CAM in the participants. CAM analysis was performed using univariate symbolic analysis (SA) on a series of 256 consecutive heart periods (HP) and systolic arterial pressure (SAP) values. The SA indices were no variation (0 V%), one variation, two like variations (2LV%), and two unlike variations (2UV%). Cardiovascular sympathetic modulation and cardiac parasympathetic modulation (CPM) were assessed by the indices 0 V% (for HP and SAP series) and 2LV% and 2UV% (for HP series), respectively. The mean (μ) and variance (σ) of the HP and SAP series values were also evaluated. The most relevant metabolites (VIP score > 2 in the Orthogonal partial least squares discriminant analysis) and the SA indices were subjected to the t-test (group comparison) and Pearson or Spearman correlations with p < 0.05. RESULTS: 272 molecules were obtained, of which lysoPC(20:1), indolelactate, and betaine presented higher levels (all p ≤ 0.001), while glycochenodeoxycholic acid (p < 0.001) lower levels in active subjects. Additionally, for CAM indices, active subjects showed higher levels of μHP (p < 0.001), σSAP (p = 0.015), and 2UV%HP (p = 0.002). Furthermore, LysoPC(20:1) and indolelactate had the highest correlations: μHP (LysoPC: r = 0.555; indolelactate: r = 0.492), σHP (LysoPC: r = 0.302), 2UV%HP (indolelactate: r = 0.392), and 2LV%HP (LysoPC: r = -0.406). CONCLUSIONS: Higher values of indices related to CPM and metabolites with anti-inflammatory, antioxidant and cardioprotective properties are observed in individuals who practice regular physical activity. In addition, such metabolites are associated with CAM. The authors thank São Paulo Research Foundation (FAPESP) (grant number: 2018/25082-3, 2023/09582-4, 2023/01626-2, and 2016/22215-7) and Coordination for the Improvement of Higher Education Personnel (CAPES) (Finance Code 001) for the financial support.