# Metabolic signatures of the integrated profile of cardiovascular autonomic modulation and cardiorespiratory fitness in apparently healthy individuals

**Authors:** Étore De Favari Signini, Alex Castro, Patrícia Rehder‐Santos, Juliana Cristina Milan‐Mattos, Juliana Magalhães de Oliveira, Alberto Porta, Renato Lajarim Carneiro, Antônio Gilberto Ferreira, Regina Vincenzi Oliveira, Aparecida Maria Catai

PMC · DOI: 10.14814/phy2.70739 · 2026-01-26

## TL;DR

This study identifies specific metabolites linked to heart and fitness profiles in healthy people, revealing metabolic patterns that reflect cardiovascular health.

## Contribution

The study discovers sex-specific metabolic signatures associated with integrated cardiovascular autonomic and fitness profiles in healthy individuals.

## Key findings

- Low sebacic acid in females correlates with high cardiac parasympathetic modulation and cardiovascular complexity.
- Low ornithine in males is linked to high cardiac parasympathetic modulation, baroreflex sensitivity, and cardiorespiratory fitness.
- Metabolites like choline and glucose show negative correlations with cardiovascular health metrics in females and males respectively.

## Abstract

Cardiovascular autonomic modulation (CAM) and cardiorespiratory fitness (CRF) are well‐established predictors of health. Identifying metabolites associated with integrated CAM‐CRF profiles may help characterize healthy physiological states. This study aimed to investigate metabolic signatures representing distinct CAM‐CRF profiles in apparently healthy individuals. Non‐obese individuals (n = 127, 43 ± 14 years) underwent fasting blood collection for serum metabolome (SM) analysis, cardiovascular assessment, and a cardiopulmonary exercise test to access CAM and CRF. CAM‐CRF profiles were obtained separately by sex using principal components analysis (PCA) of CAM and CRF. Subjects' scores from the first two principal components of the PCA were used to generate the groups. Groups' SM were compared using one‐way ANOVA (controlling for age) and metabolite correlations were analyzed using the subjects' scores (controlling for age and body mass index), considering p < 0.01. In females, low sebacic acid levels were associated with high cardiac parasympathetic modulation (CPM) and greater cardiovascular complexity. In males, low ornithine levels corresponded to a profile with high CPM, baroreflex sensitivity (BRS), and CRF. Choline, betaine, N,N‐dimethylglycine levels in females, and glucose and sarcosine in males, were negatively correlated with CPM, BRS, CRF and cardiovascular complexity. These metabolites reflect integrated CAM‐CRF conditions, enhancing the understanding of underlying metabolic profiles.

## Linked entities

- **Chemicals:** sebacic acid (PubChem CID 5192), ornithine (PubChem CID 389), choline (PubChem CID 305), betaine (PubChem CID 247), N,N-dimethylglycine (PubChem CID 673), glucose (PubChem CID 5793), sarcosine (PubChem CID 1088)

## Full-text entities

- **Diseases:** cardiovascular complexity (MESH:D002318), obese (MESH:D009765)
- **Chemicals:** ornithine (MESH:D009952), sebacic acid (MESH:C011107), sarcosine (MESH:D012521), N,N-dimethylglycine (MESH:C025138), glucose (MESH:D005947), betaine (MESH:D001622), Choline (MESH:D002794)

## Figures

5 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12835618/full.md

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Source: https://tomesphere.com/paper/PMC12835618