Cardiac–Metabolic Coupling Revealed by Lipid and Energy Metabolomics Determines 80 km Endurance Performance in Yili Horses

This study aimed to investigate the regulatory mechanisms underlying the relationship between cardiac structure and function and plasma metabolic characteristics in Yili horses participating in an 80-km endurance, by integrating echocardiography, lipidomics, and energy metabolomics analyses. Twenty four competing Yili horses were selected and divided based on competition outcomes: Pre-Completion Group: PCG (<i>n</i> = 6); Post-Completion Group: PoCG (<i>n</i> = 6); Overtime Completion Group: OCG (<i>n</i> = 6); and Non-Completion Group: NCG (<i>n</i> = 6). Cardiac structural and functional parameters were assessed via echocardiography, and intergroup differences were analyzed using one-way ANOVA with a significance threshold of <i>p</i> < 0.05. Plasma lipids and energy metabolites were quantified using UPLC-MS/MS, applying screening criteria of variable importance in projection (VIP) > 1, <i>p</i> < 0.05, and fold change (FC) > 1.2 or FC < 0.833. Bioinformatics analyses were subsequently conducted to identify intergroup variations and correlations. Specifically, associations between cardiac structure/function and metabolites were examined using Pearson correlation analysis, with screening criteria of <i>p</i> < 0.05 and correlation coefficient > 0.8. The results revealed the following: (1) Regarding cardiac structure and function, the PCG group exhibited significantly superior indices, including End-diastolic left ventricular diameter (LVIDd), End-diastolic left ventricular volume (EDV), stroke volume (SV), and ejection fraction (EF), compared with OCG and NCG, and LVIDd showed a highly significant negative correlation with competition completion time. (2) In metabolomic analyses, few differential metabolites were found among groups before the competition (only 60 between PCG and NCG), whereas 234 differential lipids were detected between PoCG and PCG, mainly enriched in sphingolipid metabolism and fatty acid degradation pathways. Energy metabolites showed distinct exercise-responsive patterns, with 22 differential metabolites between PCG and NCG and 21 between PoCG and PCG, significantly enriched in amino sugar and nucleotide sugar metabolism and TCA pathways. Dynamic changes in key TCA intermediates, such as citrate and succinate, reflected enhanced aerobic oxidative metabolism during endurance exercise. (3) Carnitine C18:1, Carnitine C10:2, FFA (20:3), Cer (t17:2/23:0) and 3-phenyllactic acid were significantly correlated with cardiac indicators such as LVLD and LVFWs (<i>p</i> < 0.05). In summary, performance in the 80-km endurance of Yili horses was primarily influenced by enlarged LVIDd and EDV, as well as the regulation of sphingolipid-fatty acid metabolic pathways. Triglycerides, specific acyl compounds, and ceramides may serve as potential biomarkers for evaluating endurance performance, providing a theoretical basis for scientific training and breeding of endurance horses.