In people with heart failure, the fatty tissue deposited directly on the heart surface—known as epicardial fat—does not act merely as a passive energy reserve. It undergoes a profound metabolic transformation that enables it to actively support the failing heart.
A new study conducted in collaboration between the Laboratory of Bioactive Lipid Metabolism at IPHYS and the Institute for Clinical and Experimental Medicine in Prague, as part of the CarDia project, has been published in the prestigious journal Metabolism. The study shows that epicardial fat releases increased amounts of L‑3‑hydroxybutyrate, which can serve as an alternative “fuel” for the cardiac muscle, helping to meet its increased energy demands. This discovery opens new possibilities for developing therapeutic strategies targeting the fat tissue surrounding the heart.
For the first time, the study provides a comprehensive metabo‑lipidomic perspective on how epicardial and subcutaneous fat differ in their response to progressing heart failure. In collaboration with clinicians, the researchers analyzed adipose tissue samples from 174 patients with varying stages of heart failure and 34 healthy volunteers. Using advanced metabolomic and lipidomic techniques, they identified around 800 different metabolites in both tissue types.
The results showed that in heart failure, subcutaneous fat gradually increases lipid degradation, while epicardial fat undergoes distinct metabolic changes linked to the late phase of fatty acid oxidation within mitochondria and peroxisomes. These processes lead to elevated levels of L‑3‑hydroxybutyrate and hydroxybutyrylcarnitine in the immediate vicinity of the heart muscle. The actively released L‑3‑hydroxybutyrate may thus serve as an important energy source or signaling molecule for the failing heart.
Reference: Riecan M., Kasperova B. J., Vondrackova M., Janovska P., Haasova E., Adamcova K., Ivak P., Hlavacek D., Kroupova K., Cajka T., Kopecky J., Stemberkova Hubackova S., Mraz M., Netuka I., Melenovsky V., Haluzik M., and Kuda O.: Epicardial adipose tissue produces L-3-hydroxybutyrate in advanced heart failure: direct analysis of fat metabolic remodeling. Metabolism 175:156465 (2025). DOI:10.1016/j.metabol.2025.156465. IF = 11.9
