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World J Gastroenterol. Feb 21, 2014; 20(7): 1768-1776
Published online Feb 21, 2014. doi: 10.3748/wjg.v20.i7.1768
Role of endoplasmic reticulum stress in the pathogenesis of nonalcoholic fatty liver disease
Xue-Qun Zhang, Cheng-Fu Xu, Chao-Hui Yu, Wei-Xing Chen, You-Ming Li
Xue-Qun Zhang, Cheng-Fu Xu, Chao-Hui Yu, Wei-Xing Chen, You-Ming Li, Department of Gastroenterology, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou 310003, Zhejiang Province, China
Author contributions: Zhang XQ, Xu CF and Yu CH designed and wrote the paper; Chen WX and Li YM checked and revised the manuscript.
Supported by National Key Basic Research Development Program, No. 2012CB524905; National Science and Technology Support Plan Project, No. 2012BAI06B04; National Natural Science Foundation of China, No. 30900677, No. 81070315, No. 81070366, No. 81100278, No. 81170378, No. 81230012 and No. 81270487; Zhejiang Provincial Natural Science Foundation of China, No. Y2090463 and No. Y2110026; International Science and Technology Cooperation Projects of Zhejiang Province, No. 2013C24010; Science Foundation of Health Bureau of Zhejiang Province, No. 2009A070 and No. 2012RCA026; and Specialized Research Fund for the Doctoral Program of Higher Education, No. 20090101120110
Correspondence to: You-Ming Li, MD, Department of Gastroenterology, The First Affiliated Hospital, College of Medicine, Zhejiang University, 79 Qingchun Road, Hangzhou 310003, Zhejiang Province, China. zhangxuequn720@163.com
Telephone: +86-571-87236603 Fax: +86-571-87236611
Received: August 29, 2013
Revised: November 20, 2013
Accepted: December 5, 2013
Published online: February 21, 2014
Processing time: 195 Days and 1.7 Hours
Abstract

Nonalcoholic fatty liver disease (NAFLD) has emerged as a common public health problem in recent decades. However, the underlying mechanisms leading to the development of NAFLD are not fully understood. The endoplasmic reticulum (ER) stress response has recently been proposed to play a crucial role in both the development of steatosis and progression to nonalcoholic steatohepatitis. ER stress is activated to regulate protein synthesis and restore homeostatic equilibrium when the cell is stressed due to the accumulation of unfolded or misfolded proteins. However, delayed or insufficient responses to ER stress may turn physiological mechanisms into pathological consequences, including fat accumulation, insulin resistance, inflammation, and apoptosis, all of which play important roles in the pathogenesis of NAFLD. Therefore, understanding the role of ER stress in the pathogenesis of NAFLD has become a topic of intense investigation. This review highlights the recent findings linking ER stress signaling pathways to the pathogenesis of NAFLD.

Keywords: Endoplasmic reticulum stress; Unfolded protein response; Nonalcoholic fatty liver disease; Nonalcoholic steatohepatitis

Core tip: Nonalcoholic fatty liver disease (NAFLD) is a progressive disorder that can lead to impaired liver function and, ultimately, liver failure. Chronic endoplasmic reticulum stress induces numerous intracellular pathways that can lead to hepatic steatosis, systemic inflammation, and hepatocyte cell death, all of which are keystones of NAFLD. This review highlights the recent findings linking ER stress signaling pathways with the pathogenesis of NAFLD, which may help identify novel therapeutic targets for the prevention and treatment of NAFLD.