Integrative Metabolomic and Echocardiographic Profiling Reveals Metabolic-Cardiac Structural Coupling in Yili Horses During Incremental Exercise.

Overview

• This study combined echocardiography and metabolomics to investigate how changes in blood metabolites relate to heart structure in Yili horses during progressively intense treadmill exercise.
• The goal was to understand the metabolic and cardiac structural coupling that supports exercise performance in these horses.

Study Design and Methods

• Subjects: Nine speed-type Yili horses were selected for the exercise test.
• Exercise Protocol: Graded treadmill exercise with a 6% incline, increasing speed from 0 m/s (rest) to 9 m/s in stages (0, 3, 5, 7, and 9 m/s).
• Data Collection:
  • Blood samples were taken from the jugular vein at each speed to analyze plasma metabolites.
  • Echocardiographic measurements: Twenty structural heart parameters were recorded at rest and peak exercise.
• Metabolomics Analysis:
  • Liquid chromatography-mass spectrometry (LC-MS) was used to profile metabolites.
  • Differentially expressed metabolites (DEMs) were identified across exercise intensities.
  • 314 common DEMs were found when comparing all exercise levels, including 124 upregulated and 190 downregulated compounds.
• Statistical Analysis: Pearson correlation was used to link metabolite levels and heart structure variables.

Key Metabolite Classes and Pathways Identified

• Types of Metabolites:
  • Amino acids and derivatives
  • Organic acids
  • Fatty acyls (fatty acids and derivatives)
• Metabolic Pathways Involved:
  • ABC transporter pathway – involved in nutrient and metabolite transport across membranes
  • Thermogenesis – regulation of heat production during exercise
  • Aldosterone-regulated sodium reabsorption – important for fluid and electrolyte balance
  • Steroid hormone biosynthesis – linked to hormonal regulation of metabolism and stress
  • One-carbon folate metabolism – important for nucleotide synthesis and methylation reactions

Correlations Between Specific Metabolites and Cardiac Structural Indices

• At Rest (0 m/s):
  • Right ventricular end-diastolic dimension positively correlated with arginyl-isoleucine, suggesting a link between this dipeptide and heart chamber size.
  • Left ventricular free wall thickness during diastole and systole correlated positively with undecanedioic acid (a medium-chain dicarboxylic acid) and proline-hydroxyproline, a dipeptide involved in collagen synthesis.
• At Peak Exercise (9 m/s):
  • Left ventricular mass and mass index showed positive correlations with succinic acid and methylmalonic acid, organic acids involved in energy metabolism, indicating increased mitochondrial activity and energy flux.
  • Left ventricular minor axis dimension positively correlated with carnitine derivatives (C14:2 and C12:1), implicating enhanced fatty acid transport and oxidation in cardiac muscle during exercise.
  • Negative correlations were observed between:
    • Left ventricular end-systolic dimension and cysteine-glutathione disulfide, suggesting a role of redox homeostasis in cardiac contractility.
    • Left atrial end-diastolic dimension and N2-(1-carboxyethyl)-L-arginine, indicating complex regulation involving arginine derivatives.

Biological Implications and Interpretations

• Amino Acid Metabolites:
  • Support collagen turnover, important for maintaining the cardiac extracellular matrix and structural integrity during exercise adaptation.
  • Contribute to redox balance, protecting heart tissue from oxidative stress induced by intensive exercise.
• Organic Acids:
  • Sustain mitochondrial energy metabolism, crucial for ATP production in contracting cardiac muscle.
  • Enhance antioxidant defense, buffering exercise-induced oxidative damage.
• Fatty Acyls:
  • Serve as key energy substrates through fatty acid oxidation, supporting continuous cardiac contractile activity under increasing workload.

Significance and Applications

• The study establishes a detailed metabolic-cardiac structure relationship specific to Yili horses, linking biochemical changes to anatomical adaptations during exercise.
• This framework can inform precision training strategies by targeting metabolism to enhance cardiac performance and endurance in equine athletes.
• Metabolome-informed phenotyping allows better prediction of performance capacity and helps monitor health during conditioning and competition.