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Short-Chain Carbon Sources: Exploiting Pleiotropic Effects for Heart Failure Therapy.
Azariyas A Challa1, E Douglas Lewandowski1,2
1Division of Cardiovascular Medicine, The Ohio State University College of Medicine, Columbus, Ohio, USA.
JACC. Basic to Translational Science
|August 12, 2022
Summary
Ketone bodies (KBs) and short-chain fatty acids (SCFAs) show promise for heart failure (HF) treatment. Beyond fuel, their signaling roles in inflammation and oxidative stress offer new therapeutic avenues for HF patients.
Area of Science:
- Cardiology
- Metabolic Research
- Biochemistry
Background:
- Heart failure (HF) is a major cause of death, necessitating new treatments.
- Sodium-glucose cotransporter-2 inhibitors show benefits in HF, possibly via ketone body (KB) oxidation.
- Short-chain fatty acids (SCFAs) are preferentially oxidized over KBs in failing hearts.
Purpose of the Study:
- To review the metabolic and nonmetabolic roles of KBs and SCFAs in heart failure.
- To explore the therapeutic potential of KBs and SCFAs for HF with reduced and preserved ejection fraction.
Main Methods:
- Literature review of recent studies on KB and SCFA metabolism and function in HF.
- Analysis of evidence regarding nonmetabolic effects, including signaling, epigenetics, inflammation, and oxidative stress.
Main Results:
- KBs and SCFAs serve as alternative energy sources for the failing heart.
- Both KBs and SCFAs possess significant nonmetabolic functions impacting cellular processes.
- Evidence suggests these molecules influence inflammation, immunity, blood pressure, and oxidative stress.
Conclusions:
- The metabolic and nonmetabolic activities of KBs and SCFAs offer a promising therapeutic strategy for HF.
- Targeting KB and SCFA pathways may benefit patients with both HF with reduced ejection fraction and HF with preserved ejection fraction.
Keywords:
BP, blood pressureCPT1, carnitine palmitoyltransferase ICoA, coenzyme AFFAR, free fatty acid receptorGPR, G protein–coupled receptorHF, heart failureHFpEFHFpEF, heart failure with preserved ejection fractionHFrEFKB, ketone bodyLCFA, long-chain fatty acidSCFA, short-chain fatty acidSGLT2, sodium-glucose cotransporter-2heart failureketonesshort-chain fatty acidsβ-HB, β-hydroxybutyrate
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