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Data sharing statement: No additional unpublished data are available.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
Abstract
AIM

To determine the role of G0/G1 switch gene 2 (G0S2) and its transcriptional regulation in palmitate-induced hepatic lipid accumulation.

METHODS

HepG2 cells were treated with palmitate, or palmitate in combination with CCAAT/enhancer binding protein (C/EBP)β siRNA or G0S2 siRNA. The mRNA expression of C/EBPβ, peroxisome proliferator-activated receptor (PPAR)γ and PPARγ target genes (G0S2, GPR81, GPR109A and Adipoq) was examined by qPCR. The protein expression of C/EBPβ, PPARγ, and G0S2 was determined by Western blotting. Lipid accumulation was detected with Oil Red O staining and quantified by absorbance value of the extracted Oil Red O dye. Lipolysis was evaluated by measuring the amount of glycerol released into the medium.

RESULTS

Palmitate caused a dose-dependent increase in lipid accumulation and a dose-dependent decrease in lipolysis in HepG2 cells. In addition, palmitate increased the mRNA expression of C/EBPβ, PPARγ, and PPARγ target genes (G0S2, GPR81, GPR109A, and Adipoq) and the protein expression of C/EBPβ, PPARγ, and G0S2 in a dose-dependent manner. Knockdown of C/EBPβ decreased palmitate-induced PPARγ and its target genes (G0S2, GPR81, GPR109A, and Adipoq) mRNA expression and palmitate-induced PPARγ and G0S2 protein expression in HepG2 cells. Knockdown of C/EBPβ also attenuated lipid accumulation and augmented lipolysis in palmitate-treated HepG2 cells. G0S2 knockdown attenuated lipid accumulation and augmented lipolysis, while G0S2 knockdown had no effects on the mRNA expression of C/EBPβ, PPARγ, and PPARγ target genes (GPR81, GPR109A and Adipoq) in palmitate-treated HepG2 cells.

CONCLUSION

Palmitate can induce lipid accumulation in HepG2 cells by activating C/EBPβ-mediated G0S2 expression.

Keywords: Obesity, Nonalcoholic fatty liver disease, Saturated fatty acid, G0/G1 switch gene 2, CCAAT/enhancer binding protein β, Adipogenesis, Lipolysis, Proliferator-activated receptor γ

Core tip: Obesity-associated nonalcoholic fatty liver disease 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) is a critical regulator of hepatic lipid accumulation. However, the role of G0S2 and its transcriptional regulation in palmitate-induced hepatic lipid accumulation is not clear. We found that palmitate can induce lipid accumulation in HepG2 cells by activating C/EBPβ-mediated G0S2 expression.