Metabolic Heterogeneity Across Heart Failure Subtypes Defined by Integrative Multi-Omics Analysis
Yuzhou Xue1, Lin Liu2, Ming Xu3
1Department of Cardiology and Institute of Vascular Medicine, Peking University Third Hospital, State Key Laboratory of Vascular Homeostasis and Remodeling, National Health Commission Key Laboratory of Cardiovascular Molecular Biology and Regulatory Peptides, Beijing Key Laboratory of Cardiovascular Receptors Research, Peking University, Beijing, China.
Journal of Cardiovascular Translational Research
|July 1, 2026
Summary
Distinct lipid metabolites increase heart failure (HF) risk, while tricarboxylic acid (TCA) cycle intermediates may protect. Metabolic signatures vary by HF cause, with OGDHL identified as a key regulator in cardiac remodeling.
Area of Science:
- Cardiovascular Science
- Metabolomics
- Genetics
Background:
- Heart failure (HF) is a complex syndrome with varied causes, but its specific metabolic underpinnings remain poorly understood.
- Identifying subtype-specific metabolic differences is crucial for targeted therapeutic strategies.
Purpose of the Study:
- To elucidate the metabolic signatures associated with different subtypes of heart failure.
- To identify novel molecular regulators of cardiac metabolic remodeling in HF.
Main Methods:
- Integrative multi-omics analysis combining metabolomics, genetics, and single-cell transcriptomics.
- Mendelian randomization analysis of 1,091 circulating metabolites.
- Analysis of subtype-specific metabolic pathways in coronary heart disease (CHD), hypertension (HTN), and overweight-related HF.
Main Results:
- Sphingolipids were linked to increased HF risk, whereas tricarboxylic acid (TCA) cycle intermediates showed potential protective effects.
- Distinct metabolic profiles were observed: lipid remodeling in CHD-HF, TCA metabolism in HTN-HF, and amino acid pathways in overweight-related HF.
- Candidate regulators including UPP1, NEU3, CBS, SHMT1, PLD2, OGDHL, and SULT1A1/2 were identified; OGDHL, enriched in cardiomyocytes, was downregulated in experimental HF.
Conclusions:
- Metabolic heterogeneity significantly contributes to distinct heart failure subtypes.
- OGDHL emerges as a potential key regulator of cardiac metabolic remodeling in heart failure.
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