Semin Liver Dis 2018; 38(04): 320-332
DOI: 10.1055/s-0038-1670677
Review Article
Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Unfolded Protein Response Sensors in Hepatic Lipid Metabolism and Nonalcoholic Fatty Liver Disease

Anne S. Henkel
1   Division of Gastroenterology and Hepatology, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, Illinois
› Author Affiliations
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Publication History

Publication Date:
24 October 2018 (online)

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Abstract

Activation of the hepatic unfolded protein response (UPR), a highly conserved cellular response to endoplasmic reticulum (ER) stress, is a firmly established feature of nonalcoholic fatty liver disease (NAFLD). ER stress is now widely accepted as both a cause and a consequence of hepatic steatosis. Moreover, the accumulation of hepatic lipids induces ER stress, which, in turn, disrupts hepatic lipid metabolism thus creating a vicious cycle that potentiates hepatic lipid accumulation. Additionally, there is interplay between the UPR and the inflammatory cascades associated with progressive nonalcoholic steatohepatitis. Understanding the molecular mechanisms by which the UPR regulates hepatic lipid metabolism and lipotoxic liver injury may lead to the identification of novel therapeutic targets for the treatment of NAFLD.