Basic Study
Copyright ©The Author(s) 2017. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Nov 21, 2017; 23(43): 7705-7715
Published online Nov 21, 2017. doi: 10.3748/wjg.v23.i43.7705
Palmitate induces fat accumulation by activating C/EBPβ-mediated G0S2 expression in HepG2 cells
Nai-Qian Zhao, Xiao-Yan Li, Li Wang, Zi-Ling Feng, Xi-Fen Li, Yan-Fang Wen, Jin-Xiang Han
Nai-Qian Zhao, Li Wang, Jin-Xiang Han, Department of Gerontology, the Second Hospital of Shanxi Medical University, Taiyuan 030001, Shanxi Province, China
Xiao-Yan Li, Zi-Ling Feng, Xi-Fen Li, Yan-Fang Wen, Department of Infectious Diseases, the First People’s Hospital of Jinzhong, Jinzhong 030600, Shanxi Province, China
Author contributions: Zhao NQ and Li XY contributed equally to this work. Zhao NQ and Li XY drafted and designed the study; Wang L, Feng ZL, Li XF, Wen YF and Han JX collected data and performed the majority of experiments; Li XY analyzed the data; Zhao NQ wrote the paper; All the authors participated in revision of the paper, and approved the final version to be published.
Supported by the grants from the Natural Science Foundation of Shanxi Province, China, No. 2014011043-1; and the Social Development Project of Jinzhong, Shanxi Province, No. S1601.
Institutional review board statement: No patients were involved in this study and no specimens were collected clinically, so institutional review board approval is unnecessary.
Conflict-of-interest statement: The authors declare no conflict of interest related to this study.
Data sharing statement: No additional unpublished data are available.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Dr. Nai-Qian Zhao, Department of Gerontology, the Second Hospital of Shanxi Medical University, No. 382, Wuyi Road, Taiyuan 030001, Shanxi Province, China. m18235150464@163.com
Telephone: +86-0351-3365499 Fax: +86-0351-3362716
Received: August 14, 2017
Peer-review started: August 15, 2017
First decision: August 30, 2017
Revised: September 27, 2017
Accepted: September 28, 2017
Article in press: September 28, 2017
Published online: November 21, 2017
ARTICLE HIGHLIGHTS
Research background

Obesity-associated nonalcoholic fatty liver disease (NAFLD) is characterized by excessive deposition of fat in hepatocytes. The saturated free fatty acid palmitate, the concentration of which is often elevated in obesity, is a major contributor to an increase in intrahepatic triglyceride. G0/G1 switch gene 2 (G0S2) plays an important role in regulating hepatic lipid metabolism. However, the role of G0S2 and its transcriptional regulation in palmitate-induced hepatic lipid accumulation has remained unclear.

Research motivation

This study was carried out to clarify the molecular mechanism connecting palmitate to obesity-associated NAFLD. As CCAAT/enhancer binding protein beta (C/EBPβ), proliferator-activated receptor gamma (PPARγ) and G0S2 all relate to obesity-associated NAFLD, we investigated their roles and interrelationships in palmitate-induced hepatic lipid accumulation. The results lead to important new insights into the molecular mechanism of NAFLD.

Research objectives

The goal of this study was to determine the role of G0S2 and its transcriptional regulation in palmitate-induced hepatic lipid accumulation. The results suggest a previously unknown link between C/EBPβ and G0S2 that contributes to hepatic steatosis.

Research methods

In this study, we examined lipolysis, lipid accumulation, and the expression of C/EBPβ, PPARγ and PPARγ-regulated genes (G0S2, GPR81, GPR109A and Adipoq) in response to palmitate treatment in HepG2 cells. Specifically, we investigated the relationships between expression of the aforementioned proteins and hepatocyte lipolysis and lipid accumulation by using siRNA-mediated gene knockdown experiments.

Research results

Palmitate significantly facilitated lipid accumulation and suppressed lipolysis in HepG2 cells. Palmitate also significantly increased the expression of C/EBPβ, PPARγ, and PPARγ target genes (G0S2, GPR81, GPR109A and Adipoq). C/EBPβ knockdown significantly reduced palmitate-induced PPARγ and G0S2 expression. Moreover, C/EBPβ knockdown attenuated lipid accumulation and augmented lipolysis in palmitate-treated HepG2 cells. Importantly, G0S2 knockdown significantly attenuated lipid accumulation and augmented lipolysis in palmitate-treated HepG2 cells, while G0S2 knockdown had no efects on palmitate-induced expression of C/EBPβ, PPARγ, and PPARγ target genes (GPR81, GPR109A, and Adipoq).

Research conclusions

Palmitate can induce lipid accumulation in HepG2 cells by activating C/EBPβ-mediated G0S2 expression. The result provides novel evidence linking G0S2 expression to palmitate-induced hepatic lipogenesis. Considering that liver lipid accumulation is not only a hallmark of NAFLD, but also the first and critical step in the initiation and progression of NAFLD, interfering with G0S2 may represent an effective strategy for the treatment of obesity-related hepatic steatosis.