Peroxisome proliferator-activated receptor agonists: A new hope towards the management of alcoholic liver disease

Abstract

In this editorial, we examine a paper by Koizumi et al, on the role of peroxisome proliferator-activated receptor (PPAR) agonists in alcoholic liver disease (ALD). The study determined whether elafibranor protected the intestinal barrier and reduced liver fibrosis in a mouse model of ALD. The study also underlines the role of PPARs in intestinal barrier function and lipid homeostasis, which are both affected by ALD. Effective therapies are necessary for ALD because it is a critical health issue that affects people worldwide. This editorial analyzes the possibility of PPAR agonists as treatments for ALD. As key factors of inflammation and metabolism, PPARs offer multiple methods for managing the complex etiology of ALD. We assess the abilities of PPARα, PPARγ, and PPARβ/δ agonists to prevent steatosis, inflammation, and fibrosis due to liver diseases. Recent research carried out in preclinical and clinical settings has shown that PPAR agonists can reduce the severity of liver disease. This editorial discusses the data analyzed and the obstacles, advantages, and mechanisms of action of PPAR agonists for ALD. Further research is needed to understand the efficacy, safety, and mechanisms of PPAR agonists for treating ALD.

Keywords: Alcoholic liver disease; Peroxisome proliferator-activated receptors; Peroxisome proliferator-activated receptors agonists; Liver fibrosis; Inflammation; Metabolic regulation; Hepatoprotection

Core Tip: Peroxisome proliferator-activated receptors (PPARs) are a family of nuclear receptors, including PPARα, PPARγ, and PPARβ/δ. They regulate vital factors in the development of alcoholic liver disease (ALD), like lipid metabolism, inflammation, and fibrosis. PPAR agonists have the potential to manage ALD. In recent preclinical and clinical trials, PPAR agonists have revealed their potency to eliminate liver steatosis, improve insulin receptor sensitivity, and diminish inflammation and fibrosis. However, to confirm their effectiveness and reveal side effects, larger clinical trials in ALD must be conducted. This article, therefore, raises the need for further study and debate on the application of PPAR agonists for ALD management.