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Inhibition of ghrelin o-acyltransferase attenuated lipotoxicity by inducing autophagy via AMPK-mTOR pathway 期刊论文

编号：

62787fed-3257-4190-ac14-9346be4e6f48
作者：

Zhang, Shaoren^[1];Mao, Yuqing(毛雨晴)^[1]Fan, Xiaoming(樊晓明)*^[1]
语种：

English
期刊：

DRUG DESIGN DEVELOPMENT AND THERAPY ISSN：1177-8881 2018 年 12 卷 (873 - 885)
收录：
关键词：

ghrelin o-acyltransferase GOAT high-fat diet HFD free fatty acid FFA nonalcoholic fatty liver disease NAFLD
摘要：

Background: Nonalcoholic fatty liver disease (NAFLD) has been considered the most commonly occurring chronic hepatopathy in the world. Ghrelin o-acyltransferase (GOAT) is an acylation enzyme which has an acylated position 3 serine on ghrelin. Recent investigation revealed that activated autophagy could attenuate liver steatosis. The aim of this study was to explore therapeutic roles that inhibit GOAT exerted in NAFLD, and its potential association with autophagy. Materials and methods: Human LO2 cells were pretreated with siRNA-GOAT to induce liver steatosis using free fatty acids (FFAs). A chronic NAFLD model was established by feeding male mice C57bl/6 with high-fat diet (HFD) for 56 days with GO-CoA-Tat administrated subcutaneously. Lipid droplets were identified by Oil Red O stains. Body weight (BW) of mice was measured every week. Autophagy, tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6), serum biochemical indicators (glucose [Glu], total cholesterol [TC], triglyceride [TG], aspartate aminotransferase [AST], alanine aminotransferase [ALT]) and signaling pathway proteins of phosphorylated AMPK-mTOR were measured. Results: The TG contents of the FFA and HFD groups were decreased by the inhibition of GOAT. Among mice treated with GO-CoA-Tat and siRNA-GOAT, IL-6 and TNF-alpha concentrations were remarkably decreased. Indicators of liver injury such as ALT and AST were also remarkably decreased among mice treated with GO-CoA-Tat. Likewise, GO-CoA-Tat significantly reduced the BW of mice and serum TG, TC and Glu. Autophagy was induced along with reduced lipids in the cells of the FFA and HFD groups. The inhibition of GOAT upregulated autophagy via AMPK-mTOR restoration. Conclusion: These results indicate that the inhibition of GOAT attenuates lipotoxicity by autophagy stimulation via AMPK-mTOR restoration and offers innovative evidence for using GO-CoA-Tat or siRNA-GOAT in NAFLD clinically.
推荐引用方式
GB/T 7714：

Zhang Shaoren,Mao Yuqing,Fan Xiaoming, et al. Inhibition of ghrelin o-acyltransferase attenuated lipotoxicity by inducing autophagy via AMPK-mTOR pathway [J].DRUG DESIGN DEVELOPMENT AND THERAPY,2018,12:873-885.
APA：

Zhang Shaoren,Mao Yuqing,Fan Xiaoming.(2018).Inhibition of ghrelin o-acyltransferase attenuated lipotoxicity by inducing autophagy via AMPK-mTOR pathway .DRUG DESIGN DEVELOPMENT AND THERAPY,12:873-885.
MLA：

Zhang Shaoren, et al. "Inhibition of ghrelin o-acyltransferase attenuated lipotoxicity by inducing autophagy via AMPK-mTOR pathway" .DRUG DESIGN DEVELOPMENT AND THERAPY 12(2018):873-885.

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