2026/04/30 by Steven M. Claypool, Carla M Koehler · 1 voice
Biochemistry, Genetics and Molecular Biology · Medicine · #Cardiovascular Function and Risk Factors #Mitochondrial Function and Pathology #Peroxisome Proliferator-Activated Receptors
paper · doi:10.1172/jci204459
openalex publication_date 2026/04/30 · openalex created_date 2026/05/02 · openalex updated_date 2026/07/22
Fatty acid oxidation (FAO) provides the healthy heart with 60%-90% of its ATP, with the remainder coming from metabolism of glucose. Metabolic flexibility is key to heart function, ensuring an uninterrupted source of fuel. In heart failure, a shift from FAO to glucose-dependent metabolism occurs as disease progresses, supporting the widely held notion that fat is the optimal substrate in the heart. In this issue of the JCI, Kim et al. challenge this assumption. In studies of acetyl-CoA carboxylase-deficient (ACC-deficient) mice, they found that unregulated use of fat as a substrate led to cardiac damage. ACC-deficient mice developed cardiolipin deficiency as a result of excessive FAO depleting stores of linoleic acid, which is used as a substrate for cardiolipin maturation. The resulting mitochondrial dysfunction was associated with dilated cardiomyopathy and heart failure in these mice. The findings highlight potential for development of therapeutic strategies that balance energy sources and replenish cardiolipin levels.