期刊
JOURNAL OF HEPATOLOGY
卷 69, 期 4, 页码 927-947出版社
ELSEVIER SCIENCE BV
DOI: 10.1016/j.jhep.2018.06.008
关键词
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资金
- AFEF
- SFD
- ARC [20171206287]
- La Ligue Contre le Cancer
- French Government (National Research Agency, ANR) through the 'Investments for the Future' LABEX SIGNALIFE: program [ANR-11-LABX-0028-01, ANR-15-CE14-0016-01]
- Institut National Du Cancer (INCa) [PLBIO: 2017, PLBIO: 2015-111, INCA_7981]
- FONDECYT [3180427, 1140549]
- FONDAP program [15150012]
- Millennium Institute [P09-015-F]
- European Commission RD MSCA-RISE [734749]
- Michael J Fox Foundation for Parkinson's Research - Target Validation grant [9277]
- FONDEF [ID16I10223, D11E1007]
- US Office of Naval Research-Global (ONR-G) [N62909-16-1-2003]
- U.S. Air Force Office of Scientific Research [FA9550-16-1-0384]
- ALSRP Therapeutic Idea Award [AL150111]
- Muscular Dystrophy Association [382453]
- CONICYT-Brazil [441921/2016-7]
- EU H2020 MSCA [ITN-675448, RISE-734749]
- Marie Curie Actions (MSCA) [734749] Funding Source: Marie Curie Actions (MSCA)
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. (C) 2018 Published by Elsevier B.V. on behalf of European Association for the Study of the Liver.
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