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World J Gastroenterol. Dec 28, 2022; 28(48): 6909-6921
Published online Dec 28, 2022. doi: 10.3748/wjg.v28.i48.6909
Nuclear factor erythroid 2-related factor 2-mediated signaling and metabolic associated fatty liver disease
Vidyasagar Naik Bukke, Archana Moola, Gaetano Serviddio, Gianluigi Vendemiale, Francesco Bellanti
Vidyasagar Naik Bukke, Archana Moola, Gaetano Serviddio, Gianluigi Vendemiale, Francesco Bellanti, Department of Medical and Surgical Sciences, University of Foggia, Foggia 71122, Italy
Author contributions: Bukke VN and Moola A collected information for the review and provided a significant contribution in writing the manuscript; The senior authors Serviddio G, Vendemiale G, and Bellanti F drafted and supervised the paper.
Conflict-of-interest statement: All authors declare no conflicts of interests 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: Francesco Bellanti, MD, PhD, Associate Professor, Department of Medical and Surgical Sciences, University of Foggia, 1 Viale Pinto, Foggia 71122, Italy. francesco.bellanti@unifg.it
Received: September 18, 2022
Peer-review started: September 18, 2022
First decision: October 30, 2022
Revised: November 5, 2022
Accepted: November 22, 2022
Article in press: November 22, 2022
Published online: December 28, 2022
Abstract

Oxidative stress is a key driver in the development and progression of several diseases, including metabolic associated fatty liver disease (MAFLD). This condition includes a wide spectrum of pathological injuries, extending from simple steatosis to inflammation, fibrosis, cirrhosis, and hepatocellular carcinoma. Excessive buildup of lipids in the liver is strictly related to oxidative stress in MAFLD, progressing to liver fibrosis and cirrhosis. The nuclear factor erythroid 2-related factor 2 (NRF2) is a master regulator of redox homeostasis. NRF2 plays an important role for cellular protection by inducing the expression of genes related to antioxidant, anti-inflammatory, and cytoprotective response. Consistent evidence demonstrates that NRF2 is involved in every step of MAFLD deve-lopment, from simple steatosis to inflammation, advanced fibrosis, and ini-tiation/progression of hepatocellular carcinoma. NRF2 activators regulate lipid metabolism and oxidative stress alleviating the fatty liver disease by inducing the expression of cytoprotective genes. Thus, modulating NRF2 activation is crucial not only in understanding specific mechanisms underlying MAFLD progression but also to characterize effective therapeutic strategies. This review outlined the current knowledge on the effects of NRF2 pathway, modulators, and mechanisms involved in the therapeutic implications of liver steatosis, inflammation, and fibrosis in MAFLD.

Keywords: Nonalcoholic fatty liver disease, Metabolic-associated fatty liver disease, Nuclear factor erythroid 2-related factor 2, Oxidative stress, Antioxidants, Liver injury

Core Tip: This updated literature review contributes to the role of nuclear factor erythroid 2-related factor 2 in combating inflammation, oxidative stress, steatosis, and fibrosis in metabolic associated fatty liver disease. There are several reviews that elucidated the advantages of nuclear factor erythroid 2-related factor 2 in human diseases, but this is the first review reporting the broad range of nuclear factor erythroid 2-related factor 2 modulators and their therapeutic implications in metabolic associated fatty liver disease.