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Copyright ©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Apr 14, 2024; 30(14): 1968-1981
Published online Apr 14, 2024. doi: 10.3748/wjg.v30.i14.1968
Necroptosis contributes to non-alcoholic fatty liver disease pathoetiology with promising diagnostic and therapeutic functions
Hong-Ju Sun, Bo Jiao, Yan Wang, Yue-Hua Zhang, Ge Chen, Zi-Xuan Wang, Hong Zhao, Qing Xie, Xiao-Hua Song
Hong-Ju Sun, Bo Jiao, Department of General Medicine, Qingdao Central Hospital, University of Health and Rehabilitation Sciences (Qingdao Central Medical Group), Qingdao 266042, Shandong Province, China
Yan Wang, Ge Chen, Zi-Xuan Wang, Hong Zhao, Xiao-Hua Song, Department of Gastroenterology, Qingdao Central Hospital, University of Health and Rehabilitation Sciences (Qingdao Central Medical Group), Qingdao 266042, Shandong Province, China
Yue-Hua Zhang, Department of Medical Administration, Qingdao Central Hospital, University of Health and Rehabilitation Sciences (Qingdao Central Medical Group), Qingdao 266042, Shandong Province, China
Ge Chen, Zi-Xuan Wang, Qingdao Medical College, Qingdao University, Qingdao 266042, Shandong Province, China
Qing Xie, Department of Infectious Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China
Co-corresponding authors: Qing Xie and Xiao-Hua Song.
Author contributions: Sun HJ, Jiao B, Xie Q, and Song XH designed the research and supervised the study; Wang Y, Zhang YH, Chen G, Wang ZX, and Zhao H performed the source searching and determined included material; Jiao B, Wang Y, Wang ZX, and Zhao H contributed interpretation of included material; Sun HJ, Jiao B, Zhang YH, Chen G, Xie Q, and Song XH prepared the primary draft of the manuscript; and all authors read and approved the final version of the article. Due to the identical collaboration of Xie Q and Song XH, both authors were considered as co-corresponding authors. Song XH was determined as the responsible author for submission of the manuscript and submission of peer review and publication processes.
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: Xiao-Hua Song, PhD, Professor, Department of Gastroenterology, Qingdao Central Hospital, University of Health and Rehabilitation Sciences (Qingdao Central Medical Group), No. 127 Siliu South Road, Qingdao 266042, Shandong Province, China. sxh72@sina.com
Received: January 6, 2024
Peer-review started: January 6, 2024
First decision: February 2, 2024
Revised: February 15, 2024
Accepted: March 25, 2024
Article in press: March 25, 2024
Published online: April 14, 2024
Abstract

Nonalcoholic fatty liver disease (NAFLD) is the most prevalent type of chronic liver disease. However, the disease is underappreciated as a remarkable chronic disorder as there are rare managing strategies. Several studies have focused on determining NAFLD-caused hepatocyte death to elucidate the disease pathoetiology and suggest functional therapeutic and diagnostic options. Pyroptosis, ferroptosis, and necroptosis are the main subtypes of non-apoptotic regulated cell deaths (RCDs), each of which represents particular characteristics. Considering the complexity of the findings, the present study aimed to review these types of RCDs and their contribution to NAFLD progression, and subsequently discuss in detail the role of necroptosis in the pathoetiology, diagnosis, and treatment of the disease. The study revealed that necroptosis is involved in the occurrence of NAFLD and its progression towards steatohepatitis and cancer, hence it has potential in diagnostic and therapeutic approaches. Nevertheless, further studies are necessary.

Keywords: Nonalcoholic fatty liver disease, Apoptosis, Necroptosis, Cell death, Diagnosis, Treatment

Core Tip: Hepatocyte death has been hypothesized as a major contributor to nonalcoholic fatty liver disease (NAFLD) progression, however, the role of regulated cell death (RCD) programs in NAFLD pathophysiology and their potential as diagnostic/therapeutic strategies has not been comprehensively discussed. The present study reviewed the participation of pyroptosis, ferroptosis, and necroptosis in the establishment of NAFLD and its progression toward steatohepatitis and cancer and discussed the potential RCDs in the diagnosis/treatment of the disease. Particularly, the present findings revealed that necroptosis significantly contributes to NAFLD occurrence and progress that may represent promising functions as diagnostic/therapeutic tools.