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비알코올성 지방간 질환과 소포체 스트레스

Nonalcoholic Fatty Liver Disease and Endoplasmic Reticulum Stress

송명준
대한내과학회 (The Korean Association Of Internal Medicine)|2021.04|대한내과학회지 (The Korean Journal of Medicine)|제96권 제2호|pp. 92-100|DOI https://doi.org/10.3904/kjm.2021.96.2.92

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키워드

Endoplasmic reticulumNon-alcoholic fatty liver diseaseUnfolded protein response
주제분류내과학

초록

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.

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.

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