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Dihydroceramide is a key metabolite that regulates autophagy and promotes fibrosis in hepatic steatosis model

Cited 20 time in Web of Science Cited 18 time in Scopus
Authors
Lee, Ah Young; Lee, Jae Won; Kim, Ji-Eun; Mock, Hyuck Jun; Park, Sungjin; Kim, Sang Wha; Hong, Seong-Ho; Kim, Ji-Young; Park, Eun-Jung; Kang, Kyung Sun; Kim, Kwang Pyo; Cho, Myung-Haing
Issue Date
2017-12
Citation
Biochemical and Biophysical Research Communications, Vol.494 No.3-4, pp.460-469
Keywords
DihydroceramideAutophagyNAFLDFibrosisFatty acid/MetabolismSphingolipids
Abstract
Non-alcoholic fatty liver disease (NAFLD) is an increasingly common chronic liver disease worldwide. Sphingolipids are a family of lipids that play essential roles as critical regulators in metabolic disorders. Some sphingolipids are known key factors in metabolic dysfunction. However, the precise effect of dihydroceramide on NAFLD remains unknown. Here, we report how dihydroceramide in autophagosome accumulation activates fibrogenesis in human liver Chang cells treated with free fatty acids (FFA). According to LC/MS lipid profiling, FFA increased the levels of sphingolipids and triacylglycerol (TG). To demonstrate the potential role of dihydroceramide metabolism in autophagy, several sphingolipid synthesis inhibitors were used. Increased dihydroceramide led to impairment of autophagic flux, resulting in increased TG storage in lipid droplets (LD) and upregulated expression of fibrosis markers. Hepatic stellate cells (HSCs, LX-2 cells) were co-cultured with Chang cells to assess the potential fibrogenic response to dihydroceramide, Treatment with rapamycin recovered autophagic flux in Chang cells and fibrogenesis in the co-culture system. Our results identified a critical function of dihydroceramide metabolism in autophagy. It could play an important role in the progression of NAFLD associated with lipid over-accumulation. Therefore, preventing autophagic flux by regulating dihydroceramide could be a potential strategic approach for providing therapy for NAFLD. (C) 2017 Elsevier Inc. All rights reserved.
ISSN
0006-291X
URI
https://hdl.handle.net/10371/172325
DOI
https://doi.org/10.1016/j.bbrc.2017.10.110
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College of Veterinary Medicine (수의과대학)Dept. of Veterinary Medicine (수의학과)Journal Papers (저널논문_수의학과)
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