From Cells to High-Resolution Imaging
Using a combination of genetic analyses, cell-based experiments, preclinical models, and high-resolution imaging, the team led by Dr. Bilal Sheikh, group leader at the Helmholtz Institute for Metabolic, Obesity and Vascular Research (HI-MAG), demonstrated that bempedoic acid physically binds to PPARα. Imaging of the protein-drug complex showed that bempedoic acid coverts PPARα into its active form, triggering genes that enhance fat breakdown in liver cells.
Beyond the Liver
Importantly, this activation occurs independently of the liver-specific enzyme previously thought necessary for bempedoic acid’s activation. This suggests the drug could also influence PPARα in other tissues, including immune cells, the heart, and the kidneys.
Implications for Metabolic Health
The findings provide a potential explanation for the broader benefits of bempedoic acid beyond cholesterol reduction. PPARα plays a central role in regulating fat metabolism, inflammation, and energy balance. These results indicate that bempedoic acid could be explored in the future as a treatment for a wider range of metabolic conditions, including fatty liver disease and other disorders linked to impaired fat metabolism.
Original publication
Papa et al., 2026: Bempedoic acid directly binds and activates PPARα, Cell Metabolism, DOI: https://doi.org/10.1016/j.cmet.2025.12.018
