Endoplasmic reticulum stress signalling and the pathogenesis of non-alcoholic fatty liver disease.
J Hepatol
; 69(4): 927-947, 2018 Oct.
Article
in En
| MEDLINE
| ID: mdl-29940269
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.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Signal Transduction
/
Endoplasmic Reticulum Stress
/
Non-alcoholic Fatty Liver Disease
Type of study:
Etiology_studies
Limits:
Animals
/
Humans
Language:
En
Journal:
J Hepatol
Journal subject:
GASTROENTEROLOGIA
Year:
2018
Document type:
Article
Affiliation country:
France