Format

Send to

Choose Destination
J Hepatol. 2018 Oct;69(4):927-947. doi: 10.1016/j.jhep.2018.06.008. Epub 2018 Jun 27.

Endoplasmic reticulum stress signalling and the pathogenesis of non-alcoholic fatty liver disease.

Author information

1
Université Côte d'Azur, INSERM, U1065, C3M, 06200 Nice, France.
2
Biomedical Neuroscience Institute (BNI), Faculty of Medicine, University of Chile, Santiago, Chile; Center for Geroscience, Brain Health and Metabolism (GERO), Santiago, Chile; Program of Cellular and Molecular Biology, Institute of Biomedical Sciences, University of Chile, Santiago, Chile.
3
Biomedical Neuroscience Institute (BNI), Faculty of Medicine, University of Chile, Santiago, Chile; Center for Geroscience, Brain Health and Metabolism (GERO), Santiago, Chile; Program of Cellular and Molecular Biology, Institute of Biomedical Sciences, University of Chile, Santiago, Chile; Buck Institute for Research on Aging, Novato, CA 94945, USA; Department of Immunology and Infectious Diseases, Harvard School of Public Health, 02115 Boston, MA, USA.
4
"Chemistry, Oncogenesis, Stress, Signaling", Inserm U1242, Université de Rennes, Rennes, France; Centre de Lutte Contre le Cancer Eugène Marquis, Rennes, France.
5
Université Côte d'Azur, INSERM, U1065, C3M, 06200 Nice, France. Electronic address: beatrice.bailly-maitre@unice.fr.

Abstract

The global epidemic of obesity has been accompanied by a rising burden of non-alcoholic fatty liver disease (NAFLD), with manifestations ranging from simple steatosis to non-alcoholic steatohepatitis, potentially developing into hepatocellular carcinoma. Although much attention has focused on NAFLD, its pathogenesis remains largely obscure. The hallmark of NAFLD is the hepatic accumulation of lipids, which subsequently leads to cellular stress and hepatic injury, eventually resulting in chronic liver disease. Abnormal lipid accumulation often coincides with insulin resistance in steatotic livers and is associated with perturbed endoplasmic reticulum (ER) proteostasis in hepatocytes. In response to chronic ER stress, an adaptive signalling pathway known as the unfolded protein response is triggered to restore ER proteostasis. However, the unfolded protein response can cause inflammation, inflammasome activation and, in the case of non-resolvable ER stress, the death of hepatocytes. Experimental data suggest that the unfolded protein response influences hepatic tumour development, aggressiveness and response to treatment, offering novel therapeutic avenues. Herein, we provide an overview of the evidence linking ER stress to NAFLD and discuss possible points of intervention.

KEYWORDS:

Cell death; Endoplasmic Reticulum Stress; Inflammation; Liver Cancer; Steatohepatitis; Steatosis; Therapeutic Targets; Unfolded Protein Response

PMID:
29940269
DOI:
10.1016/j.jhep.2018.06.008

Supplemental Content

Full text links

Icon for Elsevier Science
Loading ...
Support Center