Pirola L. Elafibranor, a dual PPARα and PPARδ agonist, reduces alcohol-associated liver disease: Lessons from a mouse model. World J Gastroenterol 2025; 31(4): 99312 [PMID: 39877705 DOI: 10.3748/wjg.v31.i4.99312]
Corresponding Author of This Article
Luciano Pirola, PhD, Researcher, Carmen Laboratory, INSERM Unit 1060-Lyon 1 University, CENS ELI-2D Building, 165 Chemin du Grand Revoyet, Pierre Benite 69310, France. luciano.pirola@univ-lyon1.fr
Research Domain of This Article
Gastroenterology & Hepatology
Article-Type of This Article
Letter to the Editor
Open-Access Policy of This Article
This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
World J Gastroenterol. Jan 28, 2025; 31(4): 99312 Published online Jan 28, 2025. doi: 10.3748/wjg.v31.i4.99312
Elafibranor, a dual PPARα and PPARδ agonist, reduces alcohol-associated liver disease: Lessons from a mouse model
Luciano Pirola
Luciano Pirola, Carmen Laboratory, INSERM Unit 1060-Lyon 1 University, Pierre Benite 69310, France
Author contributions: Pirola L conceived and wrote the manuscript.
Conflict-of-interest statement: The author declares no conflicts of interest.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Luciano Pirola, PhD, Researcher, Carmen Laboratory, INSERM Unit 1060-Lyon 1 University, CENS ELI-2D Building, 165 Chemin du Grand Revoyet, Pierre Benite 69310, France. luciano.pirola@univ-lyon1.fr
Received: July 19, 2024 Revised: November 13, 2024 Accepted: November 20, 2024 Published online: January 28, 2025 Processing time: 163 Days and 21.8 Hours
Abstract
Metabolic dysfunction-associated steatotic liver disease (MASLD) is a highly prevalent liver pathology in need of novel pharmacological treatments to complement lifestyle-based interventions. Nuclear receptor agonists have been under scrutiny as potential pharmacological targets and as of today, resmetirom, a thyroid hormone receptor b agonist, is the only approved agent. The dual PPAR α and δ agonist elafibranor has also undergone extensive clinical testing, which reached the phase III clinical trial but failed to demonstrate a beneficial effect on MASLD. As alcohol-associated liver disease and MASLD can be interconnected, whether elafibranor might be affective against liver disease caused by alcohol consumption is worth investigating. Writing recently in the World Journal of Gastroenterology, Koizumi et al reported using a mouse model of alcohol-associated liver disease and found that hepatic steatosis, liver fibrosis, and hepatocyte apoptosis were alleviated by administration of elafibranor. Although preclinical in nature, these data support the potential beneficial action of elafibranor in alcohol-induced MASLD, warranting the testing of this molecule in patients with steatotic liver disease caused by alcohol consumption.
Core Tip: Metabolic dysfunction-associated steatotic liver disease needs novel pharmacological treatments. Elafibranor, a PPAR agonist, remains a promising molecule against steatotic liver disease caused by alcohol consumption. Koizumi et al reported, in World Journal of Gastroenterology, on their use of a mouse model of alcohol-associated liver disease which indicated that hepatic steatosis, liver fibrosis, and hepatocyte apoptosis were alleviated by administration of elafibranor. These data support the potential beneficial action of elafibranor, warranting clinical testing.
