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Front. Pharmacol. | doi: 10.3389/fphar.2019.00949

Ethanol-induced hepatic insulin resistance is ameliorated by methyl ferulic acid through the PI3K/AKT signaling pathway

 Qi Cheng1, Wen Y. Li1, Fang C. Yang1, Juan Y. Zhong1 and Li Li1*
  • 1Guilin Medical University, China

One of the key event during the development of alcoholic liver disease (ALD) is that alcohol inhibits the insulin signaling pathway in liver and leads to disorders of glucose and lipid metabolism. Methyl ferulic acid (MFA) is a biologically active monomer isolated from the root of Securidaca inappendiculata hasskarl. It has been reported that MFA has a hepatoprotective effect against alcohol-induced liver injury in vivo and in vitro. However, the effect of MFA on ethanol-induced insulin resistance in alcoholic liver disease (ALD) remains unclear. In this study, we investigated whether MFA could exert protective effects against hepatic insulin resistance in ethanol-induced L-02 cells and ALD rats. ALD was induced in vivo by feeding a Lieber-DeCarli diet containing 5% (w/v) alcohol for 16 weeks in Sprague-Dawley rats. Insulin resistance was induced in vitro in human hepatocyte L-02 cells with 200 mM ethanol for 24 h followed by 10-7 nM insulin for 30 min. MFA exhibited the effects of inhibited insulin resistance, reduced the enzymatic capacity for hepatic gluconeogenesis and increased hepatic glycogen synthesis both in vivo and in vitro. In addition, the results of transcriptome sequencing of liver tissues in the ethanol group and MFA-treated group indicated that "pyruvate metabolism", "glycolysis/gluconeogenesis" and "fatty acid metabolism" were significantly different in the ethanol group and MFA-treated group. Further studies suggested that MFA activated the hepatic phosphatidylinositol 3-kinase (PI3K)/AKT pathway in vivo and in vitro. Taken together, these findings suggested that MFA effectively ameliorated hepatic insulin resistance in alcoholic liver disease at least partially through acting on the PI3K/AKT pathway.

Keywords: Alcoholic liver disease (ALD), Insulin Resistance, Methyl ferulic acid, PI3K/Akt pathway, Glucose and lipid metabolism disorder

Received: 03 Jun 2019; Accepted: 25 Jul 2019.

Edited by:

Ewa K. Szczepanska-Sadowska, Medical University of Warsaw, Poland

Reviewed by:

Robert A. Harris, University of Kansas Medical Center, United States
Szu-Chuan Shen, National Taiwan Normal University, Taiwan  

Copyright: © 2019 Cheng, Li, Yang, Zhong and Li. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Mrs. Li Li, Guilin Medical University, Guilin, China, 31910753@qq.com