Circ Res. 2026 Jun 5;138(12):e327471. doi: 10.1161/CIRCRESAHA.126.327471. Epub 2026 Jun 4.
ABSTRACT
Although studied for decades, metabolic therapies that target cardiac lipid metabolism are underdeveloped, and most approaches have thus far failed as a heart failure treatment. In contrast, new therapies for diabetes and obesity are widely used for the prevention and treatment of heart failure. The heart depends heavily on lipid uptake and utilization for proper function. Too much or too little cardiac lipid catabolism becomes detrimental and causes heart failure, either due to lipotoxicity or energetic depletion. For this reason, cardiac lipid metabolism is carefully controlled and balanced. Moreover, cardiac fatty acid oxidation affects systemic energy metabolism, as evidenced by changes in circulating levels of fatty acids and lipoproteins. This review describes mechanisms of regulation of lipid uptake and metabolism by cardiomyocytes, how fatty acid and glucose use are coordinated, how mitochondrial fatty acid metabolism is regulated at the transcriptional and posttranslational levels, as well as how fed/fasting cycles and circadian clocks modulate heart metabolism during the day. We review studies that used cultured cells, animal models, human tissue, and nuclear tracing. Our objective is to present current knowledge on mechanisms that control cardiac lipid metabolism, thereby suggesting experimental directions that could lead to new metabolic therapies.
PMID:42241515 | DOI:10.1161/CIRCRESAHA.126.327471