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Related Experiment Video

Updated: Jan 29, 2026

Kinetic Screening of Nuclease Activity using Nucleic Acid Probes

Kinetic Screening of Nuclease Activity using Nucleic Acid Probes

Published on: November 1, 2019

Bempedoic acid directly binds and activates PPARα.

Christina Papa¹, Alina Rose¹, Hugo N G Martin¹

¹Helmholtz Institute for Metabolic, Obesity and Vascular Research (HI-MAG), Helmholtz Center Munich, 04103 Leipzig, Germany.

Cell Metabolism

|January 27, 2026

Summary

Bempedoic acid (BA) directly activates peroxisome proliferator-activated receptor alpha (PPARα), a key mechanism for its cholesterol-lowering effects. This direct activation enhances fatty acid oxidation, offering potential therapeutic benefits beyond lipid reduction.

Keywords:

PPAR cardiovascular cholesterol lipids metabolism transcription

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Area of Science:

Biochemistry
Molecular Biology
Pharmacology

Background:

Bempedoic acid (BA) is an approved lipid-lowering drug with an incompletely understood mechanism.
Understanding BA's molecular targets is crucial for optimizing its therapeutic use.

Purpose of the Study:

To elucidate the molecular mechanism of action for bempedoic acid (BA).
To investigate the direct interaction between BA and its cellular targets.
To determine the role of peroxisome proliferator-activated receptor alpha (PPARα) in BA's effects.

Main Methods:

Transcriptomic analysis to assess gene expression changes.
Biochemical assays to measure enzyme activity and lipid metabolism.
X-ray crystallography to determine the structural basis of drug-target interaction.

Main Results:

Bempedoic acid (BA) directly binds to and activates peroxisome proliferator-activated receptor alpha (PPARα).
BA treatment robustly induced PPARα signaling and fatty acid oxidation in hepatocytes and mouse liver.
X-ray crystallography revealed BA stabilizes the active conformation of PPARα.
BA activated PPARα target genes independently of ACSVL1, and this activation required PPARα.

Conclusions:

Direct activation of PPARα is a key mechanism underlying bempedoic acid's (BA) lipid-lowering effects.
This study provides a molecular basis for BA's action and suggests potential for broader therapeutic applications.
The findings highlight PPARα as a direct target for BA, independent of its conversion to bempedoyl-CoA.