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Animals : an open access journal from MDPI2025; 15(22); 3251; doi: 10.3390/ani15223251

Multi-Omics Deciphers Divergent Mechanisms in Differentially Cardiac-Remodeled Yili Horses Under Conditions of Equivalent Power Output.

Abstract: Exercise performance is a critical trait for evaluating the economic and breeding value of working and athletic horses, with cardiac structure and function serving as essential physiological determinants of athletic capacity. This study aimed to investigate the multi-omics response mechanisms associated with varying degrees of cardiac remodeling under identical exercise intensity. Twenty 2-year-old Yili horses were selected and categorized based on echocardiographic parameters into a high cardiac remodeling group (BH; EDV > 500 mL, SV > 350 mL, EF > 66%) and a low cardiac remodeling group (BL; EDV < 450 mL, SV < 330 mL, EF < 64%). Blood samples were collected before and after the 1000 m constant-speed test (pre-test high cardiac remodeling group (BH, = 10), post-test high cardiac remodeling group (AH, = 10), pre-test low cardiac remodeling group (BL, = 10), post-test low cardiac remodeling group (AL, = 10)), and integrated metabolomic, transcriptomic, and miRNA profiling were conducted to systematically characterize molecular responses to exercise-induced stress. Metabolomic analysis identified a total of 1936 lipid metabolites, with the BH group exhibiting stronger post-exercise lipid mobilization and significant enrichment of sphingolipid signaling pathways. Transcriptomic and miRNA analyses further revealed that key miRNAs in the BH group, including miR-186, miR-23a/b, and the let-7 family, along with their target genes (e.g., GNB4, RGS5, ALAS2), were involved in fine regulation of cardiac electrophysiology, oxidative stress, and energy metabolism. Integrated analysis indicated that the AH vs. BH comparison uniquely enriched pathways related to glycine-serine-threonine metabolism and glycosylphosphatidylinositol (GPI)-anchor biosynthesis, whereas the AL vs. BL comparison showed unique enrichment of α-linolenic acid and arachidonic acid metabolism pathways. Ultimately, multi-omics integration identified that in the BH group, eca-let-7d, eca-let-7e, eca-miR-196b, eca-miR-2483, and eca-miR-98 regulate ALAS2 and, together with GCSH, influence the enrichment of lipids such as PS(17:0_16:1), PS(18:0_18:1), and PS(20:0_18:1). These lipids participate in glycine, serine, and threonine metabolism through complex pathways, collectively modulating energy supply, inflammatory responses, and muscle function during exercise. This study reveals the molecular mechanisms by which horses with high cardiac remodeling maintain energy homeostasis and myocardial protection during exercise.
Publication Date: 2025-11-09 PubMed ID: 41301959PubMed Central: PMC12649268DOI: 10.3390/ani15223251Google Scholar: Lookup
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  • Journal Article

Summary

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Overview

  • This study investigates how different levels of heart remodeling in Yili horses affect their molecular responses to exercise, despite exerting the same power output.
  • By integrating metabolomic, transcriptomic, and miRNA analyses, the researchers identified distinct mechanisms related to energy metabolism and cardiac function between horses with high and low cardiac remodeling.

Background and Objective

  • Exercise performance in horses is closely linked to cardiac structure and function, which influence athletic capacity and economic value.
  • Cardiac remodeling refers to structural changes in the heart often induced by exercise or physiological stress; these changes can vary in degree among individual horses.
  • The objective was to explore molecular mechanisms underlying different degrees of cardiac remodeling under the same exercise intensity.
  • Using multi-omics approaches (metabolomics, transcriptomics, miRNA profiling), the study aimed to reveal the biological pathways and regulators that enable horses with varying heart remodeling to maintain exercise performance.

Methods

  • Subjects: 20 two-year-old Yili horses divided into two groups based on echocardiographic measurements:
    • High cardiac remodeling group (BH): End-diastolic volume (EDV) > 500 mL, Stroke volume (SV) > 350 mL, Ejection fraction (EF) > 66%
    • Low cardiac remodeling group (BL): EDV < 450 mL, SV < 330 mL, EF < 64%
  • Exercise test: A 1000 m constant-speed run conducted on all horses.
  • Sampling points: Blood samples collected before and after exercise (defining BH, AH, BL, AL groups for pre-and post-exercise states).
  • Analysis performed:
    • Metabolomics to profile lipid metabolites.
    • Transcriptomics and miRNA profiling to assess gene expression and regulatory RNA molecules.
    • Integration of multi-omics data for comprehensive pathway analysis.

Key Findings

  • Metabolomics:
    • Detected 1936 lipid metabolites in total.
    • Horses in the BH group showed stronger lipid mobilization post-exercise.
    • Sphingolipid signaling pathways were significantly enriched in BH after exercise, suggesting enhanced lipid signaling and cellular regulation.
  • Transcriptomics and miRNA analysis:
    • Key miRNAs in BH group included miR-186, miR-23a/b, and members of the let-7 family which regulate genes involved in:
      • Cardiac electrophysiology
      • Oxidative stress response
      • Energy metabolism
    • Target genes such as GNB4, RGS5, and ALAS2 were linked to these regulatory processes.
  • Pathway enrichment differences:
    • Comparing post-exercise to pre-exercise in BH (AH vs. BH) revealed enrichment in glycine-serine-threonine metabolism and glycosylphosphatidylinositol (GPI)-anchor biosynthesis pathways.
    • For AL vs. BL (low remodeling group), unique enrichment was observed in α-linolenic acid and arachidonic acid metabolism pathways.
  • Integrated multi-omics insights:
    • In the BH group, key miRNAs (eca-let-7d, eca-let-7e, eca-miR-196b, eca-miR-2483, eca-miR-98) regulate ALAS2 gene expression.
    • ALAS2, along with GCSH, influences the levels of specific lipid species such as PS(17:0_16:1), PS(18:0_18:1), and PS(20:0_18:1).
    • These lipids participate in glycine, serine, and threonine metabolism, which collectively impact:
      • Energy supply to muscles
      • Inflammatory responses
      • Muscle function during exercise
    • This suggests complex molecular networks maintaining myocardial protection and energy homeostasis in highly remodeled hearts during exercise.

Significance and Conclusions

  • The study elucidates that horses with greater cardiac remodeling adapt differently at the molecular level to exercise stress, primarily via lipid metabolism and gene regulation pathways.
  • These adaptations help maintain cardiac efficiency and muscle function during intense work despite similar power output.
  • Understanding these mechanisms could assist in evaluating and selecting horses with optimal cardiac traits for athletic or working purposes.
  • The multi-omics approach offers a comprehensive view of the biological complexity underlying cardiac remodeling and exercise performance.

Cite This Article

APA
Wang T, Yang X, Ren W, Meng J, Yao X, Chu H, Yao R, Zhai M, Zeng Y. (2025). Multi-Omics Deciphers Divergent Mechanisms in Differentially Cardiac-Remodeled Yili Horses Under Conditions of Equivalent Power Output. Animals (Basel), 15(22), 3251. https://doi.org/10.3390/ani15223251

Publication

ISSN: 2076-2615
NlmUniqueID: 101635614
Country: Switzerland
Language: English
Volume: 15
Issue: 22
PII: 3251

Researcher Affiliations

Wang, Tongliang
  • College of Animal Science, Xinjiang Agricultural University, Urumqi 830052, China.
  • Xinjiang Key Laboratory of Horse Breeding and Exercise Physiology, Urumqi 830052, China.
  • Horse Industry Research Institute, Xinjiang Agricultural University, Urumqi 830052, China.
Yang, Xixi
  • College of Animal Science, Xinjiang Agricultural University, Urumqi 830052, China.
Ren, Wanlu
  • College of Animal Science, Xinjiang Agricultural University, Urumqi 830052, China.
  • Xinjiang Key Laboratory of Horse Breeding and Exercise Physiology, Urumqi 830052, China.
  • Horse Industry Research Institute, Xinjiang Agricultural University, Urumqi 830052, China.
Meng, Jun
  • College of Animal Science, Xinjiang Agricultural University, Urumqi 830052, China.
  • Xinjiang Key Laboratory of Horse Breeding and Exercise Physiology, Urumqi 830052, China.
  • Horse Industry Research Institute, Xinjiang Agricultural University, Urumqi 830052, China.
Yao, Xinkui
  • College of Animal Science, Xinjiang Agricultural University, Urumqi 830052, China.
  • Xinjiang Key Laboratory of Horse Breeding and Exercise Physiology, Urumqi 830052, China.
  • Horse Industry Research Institute, Xinjiang Agricultural University, Urumqi 830052, China.
Chu, Hongzhong
  • Xinjiang Yili Kazakh Autonomous Prefecture Animal Husbandry Station, Urumqi 835000, China.
Yao, Runchen
  • Xinjiang Yili Kazakh Autonomous Prefecture Animal Husbandry Station, Urumqi 835000, China.
Zhai, Manjun
  • College of Animal Science, Xinjiang Agricultural University, Urumqi 830052, China.
  • Xinjiang Key Laboratory of Horse Breeding and Exercise Physiology, Urumqi 830052, China.
Zeng, Yaqi
  • College of Animal Science, Xinjiang Agricultural University, Urumqi 830052, China.
  • Xinjiang Key Laboratory of Horse Breeding and Exercise Physiology, Urumqi 830052, China.
  • Horse Industry Research Institute, Xinjiang Agricultural University, Urumqi 830052, China.

Grant Funding

  • 32202667 / National Natural Science Foundation of China Youth Program
  • 2022A02013-1 / Major Science and Technology Project of Xinjiang Uygur Autonomous Region
  • ZYYD2025JD02 / Central Guidance Project for Local Science and Technology Development-(Research on the Regulation Mechanism of Horse Breeding and Athletic Performance)
  • 2024D01B40 / The Youth Science Fund of the Natural Science Foundation of Xinjiang Uygur Autonomous Region
  • XJMFY202401 / Key Laboratory of Horse Breeding and Exercise Physiology of Xinjiang Project

Conflict of Interest Statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

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