The unfolded protein response in fatty liver disease

Anne Henkel*, Richard M. Green

*Corresponding author for this work

Research output: Contribution to journalArticle

50 Scopus citations

Abstract

The unfolded protein response (UPR) is a protective cellular response activated under conditions of endoplasmic reticulum (ER) stress. The hepatic UPR is activated in several forms of liver disease including nonalcoholic fatty liver disease (NAFLD). Recent data defining the role of the UPR in hepatic lipid metabolism have identified molecular mechanisms that may underlie the association between UPR activation and NAFLD. It has become increasingly evident that the IRE1α/Xbp1 pathway of the UPR is critical for hepatic lipid homeostasis, and dysregulation of this evolutionarily conserved pathway is associated with human nonalcoholic steatohepatitis (NASH). Although increasing evidence has delineated the importance of UPR pathway signaling in fatty liver disorders, the regulation of the hepatic UPR in normal physiology and fatty liver disorders remains incompletely understood. Understanding the role of the UPR in hepatic lipid metabolism may lead to the identification of novel therapeutic targets for the treatment of NAFLD.

Original languageEnglish (US)
Pages (from-to)321-329
Number of pages9
JournalSeminars in Liver Disease
Volume33
Issue number4
DOIs
StatePublished - 2013

Keywords

  • endoplasmic reticulum stress
  • fatty liver
  • hepatic lipid metabolism
  • unfolded protein response

ASJC Scopus subject areas

  • Hepatology

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