期刊
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
卷 479, 期 3, 页码 476-481出版社
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.bbrc.2016.09.086
关键词
Non-alcoholic steatohepatitis (NASH); Fat and obesity associated (FTO) gene; Obesity; Lipotoxicity
资金
- Duke-NUS Medical School Faculty Funds
- Singapore National Medical Research Council grant [NMRC/CSA/0054/2013, NMRC/CIRG/1340/2012, NMRC/BNIG/2025/2014]
Non-alcoholic steatohepatitis (NASH) is one of the most common causes of liver failure worldwide. It is characterized by excess fat accumulation, inflammation, and increased lipotoxicity in hepatocytes. Currently, there are limited treatment options for NASH due to lack of understanding of its molecular etiology. In the present study, we demonstrate that the expression of fat mass and obesity associated gene (FTO) is significantly increased in the livers of NASH patients and in a rodent model of NASH. Furthermore, using human hepatic cells, we show that genetic silencing of FTO protects against palmitate-induced oxidative stress, mitochondrial dysfunction, ER stress, and apoptosis in vitro. Taken together, our results show that FTO may have a deleterious role in hepatic cells during lipotoxic conditions, and strongly suggest that up-regulation of FTO may contribute to the increased liver damage in NASH. (C) 2016 Elsevier Inc. All rights reserved.
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