Long noncoding RNA lncARSR promotes hepatic lipogenesis via Akt/SREBP-1c pathway and contributes to the pathogenesis of nonalcoholic steatohepatitis
- Intensive Care Unit, The Affiliated Hospital of Weifang Medical University, Weifang, Shandong, 261031 (China)
- Department of Medical Equipment, Weifang People's Hospital, Weifang, Shandong, 261000 (China)
Highlights: • The expression of lncARSR increased in NAFLD patients and mouse model. • lncARSR modulated hepatic lipid accumulation in vivo and in vitro. • SREBP-1c mediated the effect of lncARSR on lipognesis in NASH. • lncARSR regulated SREBP-1c via PI3K/Akt pathway. Non-alcoholic fatty liver disease and steatohepatitis (NAFLD and NASH) account for the majority of liver disease in industrialized countries. However, the pathogenesis still unclear. Long non-coding RNAs (lncRNAs) has been reported to be involved in various pathophysiological processes. Here, we reported a novel role of lncARSR in hepatic lipogenesis in NAFLD. The expression of lncARSR was induced both in NAFLD patients and mouse model, as well as in hepatocytes treated with fatty acid. Moreover, overexpression of lncARSR enhanced while knockdown of lncARSR ameliorated hepatic lipid accumulation in vivo and in vitro. Furthermore, the expression of genes related to fatty acid synthesis and oxidation increased with lncARSR overexpression in vivo. Mechanistically, we identified that lncARSR regulated hepatic lipogenesis via upregulating SREBP-1c, the key regulatory molecule involved in lipogenesis. Knockdown of SREBP-1c by shRNA blocked the effect of lncARSR on lipogenesis. Furthermore, we demonstrated that lncARSR regulated SREBP-1c expression by PI3K/Akt pathway. In conclusion, our data indicated that lncARSR potentially contributes to the hepatic steatosis in NAFLD, which may be a new therapeutic target against NAFLD.
- OSTI ID:
- 23137204
- Journal Information:
- Biochemical and Biophysical Research Communications, Vol. 499, Issue 1; Other Information: Copyright (c) 2018 Elsevier Inc. All rights reserved.; Country of input: International Atomic Energy Agency (IAEA); ISSN 0006-291X
- Country of Publication:
- United States
- Language:
- English
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