Epicardial adipose tissue produces L-3-hydroxybutyrate in advanced heart failure: direct analysis of fat metabolic remodeling.
Summary
In 208 human participants spanning controls to severe HFrEF, metabolomics revealed depot-specific adipose remodeling. Epicardial adipose tissue exhibited impaired late-stage fatty acid oxidation and locally increased L-3-hydroxybutyrate production, suggesting a unique epicardial fat–heart metabolic axis in advanced heart failure.
Key Findings
- Metabolomics across EAT and SAT identified depot-specific remodeling with HF progression; EAT had impaired final steps of β-oxidation.
- EAT uniquely exhibited elevated 3-hydroxybutyrate and hydroxybutyrylcarnitine; ex vivo analyses showed increased L-3-hydroxybutyrate produced by EAT.
- Findings support a metabolic crosstalk between epicardial fat and the heart in advanced HFrEF.
Clinical Implications
Epicardial fat metabolism may influence myocardial energetics in advanced HFrEF; therapies modulating ketone metabolism or EAT function (e.g., metabolic agents, weight loss strategies) could be tailored with consideration of depot-specific effects.
Why It Matters
Identifies a novel metabolic feature—L-3-hydroxybutyrate generation by epicardial fat—linking adipose remodeling to myocardial fuel supply, opening avenues for targeted metabolic modulation in heart failure.
Limitations
- Observational cross-sectional design limits causal inference and clinical endpoint linkage
- Generalisability may be limited (single-country cohorts); no interventional validation
Future Directions
Interventional studies targeting epicardial fat metabolism and ketone pathways; in vivo tracing of depot-derived metabolites to myocardium; correlation with clinical outcomes.
Study Information
- Study Type
- Cohort
- Research Domain
- Pathophysiology
- Evidence Level
- III - Human observational tissue study with multi-omics and ex vivo functional analyses
- Study Design
- OTHER