Korean J Med.  2021 Apr;96(2):92-100. 10.3904/kjm.2021.96.2.92.

Nonalcoholic Fatty Liver Disease and Endoplasmic Reticulum Stress

• Song MJ

• KMID: 2521219
• DOI: http://doi.org/10.3904/kjm.2021.96.2.92

Abstract

Nonalcoholic fatty liver disease (NAFLD) is a major public health problem with comorbidities including obesity and dyslipidemia. Although the manifestations of NAFLD range from simple steatosis to non-alcoholic steatohepatitis, these may potentially give rise to liver cirrhosis and hepatocellular carcinoma. However, the mechanisms underlying NAFLD, and the factors that determine the individual risk of disease progression, remain poorly known. The most obvious clinicopathological characteristic of NAFLD is hepatic lipid accumulation and subsequent inflammation. In hepatocytes, the endoplasmic reticulum (ER) is a critical site of protein synthesis, detoxification, lipid and glucose metabolism, and Ca²⁺ homeostasis; the ER is involved in NAFLD pathogenesis. Hepatic accumulation of lipids stresses the ER; this activates the unfolded protein response (UPR), which is classically viewed as an adaptive pathway that maintains ER homeostasis. Recent studies have revealed that UPR sensors regulate hepatic steatosis and the cellular response to lipotoxic stress. Therefore, the basic mechanisms of ER stress and UPR induction are of great interest for understanding the pathogenesis of NAFLD. The present review focuses on the roles played by ER stress and the UPR in NAFLD pathogenesis.

Keyword

Non-alcoholic fatty liver disease; Endoplasmic reticulum; Unfolded protein response