Zhang XY, Chen QJJ, Zhu F, Li M, Shang D. Dual peroxisome proliferator-activated receptor α/δ agonists: Hope for the treatment of alcohol-associated liver disease? World J Gastroenterol 2024; 30(37): 4163-4167 [PMID: 39474402 DOI: 10.3748/wjg.v30.i37.4163]
Corresponding Author of This Article
Dan Shang, MD, PhD, Associate Professor, Department of Vascular Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, No. 1277 Jiefang Avenue, Wuhan 430022, Hubei Province, China. danshang@hust.edu.cn
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. Oct 7, 2024; 30(37): 4163-4167 Published online Oct 7, 2024. doi: 10.3748/wjg.v30.i37.4163
Dual peroxisome proliferator-activated receptor α/δ agonists: Hope for the treatment of alcohol-associated liver disease?
Xin-Yang Zhang, Qin-Jun-Jie Chen, Feng Zhu, Min Li, Dan Shang
Xin-Yang Zhang, Dan Shang, Department of Vascular Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, Hubei Province, China
Qin-Jun-Jie Chen, Min Li, Department of Hepatobiliary Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, Hubei Province, China
Feng Zhu, Department of Vascular Surgery, Hubei Provincial Hospital of Traditional Chinese Medicine, Wuhan 430061, Hubei Province, China
Co-first authors: Xin-Yang Zhang and Qin-Jun-Jie Chen.
Co-corresponding authors: Min Li and Dan Shang.
Author contributions: Zhang XY and Chen QJJ contributed equally to this work and drafted the manuscript; Chen QJJ, Li M, and Shang D revised the manuscript; Zhang XY, Chen QJJ, and Zhu F collected the references; Li M and Shang D contributed equally to this work and designed the work, they are co-corresponding authors of this manuscript; all authors made the final approval of this version.
Supported byNational Natural Science Foundation of China, No. 82172754 and No. 81874208; and Natural Science Foundation Project of Hubei Province, No. 2021CFB562.
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
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: Dan Shang, MD, PhD, Associate Professor, Department of Vascular Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, No. 1277 Jiefang Avenue, Wuhan 430022, Hubei Province, China. danshang@hust.edu.cn
Received: August 1, 2024 Revised: August 30, 2024 Accepted: September 13, 2024 Published online: October 7, 2024 Processing time: 55 Days and 17.7 Hours
Abstract
In this letter, we review the article “Effects of elafibranor on liver fibrosis and gut barrier function in a mouse model of alcohol-associated liver disease”. We focus specifically on the detrimental effects of alcohol-associated liver disease (ALD) on human health. Given its insidious onset and increasing incidence, increasing awareness of ALD can contribute to reducing the prevalence of liver diseases. ALD comprises a spectrum of several different disorders, including liver steatosis, steatohepatitis, fibrosis, cirrhosis, and hepatocellular carcinoma. The pathogenesis of ALD is exceedingly complex. Previous studies have shown that peroxisome proliferator-activated receptors (PPARs) regulate lipid metabolism, glucose homeostasis and inflammatory responses within the organism. Additionally, their dysfunction is a major contributor to the progression of ALD. Elafibranor is an oral, dual PPARα and δ agonist. The effectiveness of elafibranor in the treatment of ALD remains unclear. In this letter, we emphasize the harm of ALD and the burden it places on society. Furthermore, we summarize the clinical management of all stages of ALD and present new insights into its pathogenesis and potential therapeutic targets. Additionally, we discuss the mechanisms of action of PPARα and δ agonists, the significance of their antifibrotic effects on ALD and future research directions.
Core Tip: Alcohol-associated liver disease (ALD) is a common disease with an annually increasing incidence. It is the primary cause of cirrhosis and mortality due to hepatopathy in patients from many regions worldwide. Chronic liver damage resulting from prolonged excessive alcohol consumption can lead to liver fibrosis, which may progress to cirrhosis and hepatocellular carcinoma. Strengthening awareness of the risks associated with ALD, abstaining from alcohol, and implementing early intervention are fundamental to the management of ALD.
