Basic Study
Copyright ©The Author(s) 2017. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Dec 14, 2017; 23(46): 8140-8151
Published online Dec 14, 2017. doi: 10.3748/wjg.v23.i46.8140
miR-192-5p regulates lipid synthesis in non-alcoholic fatty liver disease through SCD-1
Xiao-Lin Liu, Hai-Xia Cao, Bao-Can Wang, Feng-Zhi Xin, Rui-Nan Zhang, Da Zhou, Rui-Xu Yang, Ze-Hua Zhao, Qin Pan, Jian-Gao Fan
Xiao-Lin Liu, Hai-Xia Cao, Bao-Can Wang, Feng-Zhi Xin, Rui-Nan Zhang, Da Zhou, Rui-Xu Yang, Ze-Hua Zhao, Qin Pan and Jian-Gao Fan, Center for Fatty Liver, Department of Gastroenterology, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200092, China
Author contributions: Fan JG, Cao HX and Liu XL conceived and designed the study; Liu XL, Xin FZ, Zhang RN, Zhou D, Yang RX and Zhao ZH performed the experiments; Wang BC and Pan Q analyzed the data; Fan JG, Cao HX and Liu XL wrote the paper; Liu XL, Cao HX and Fan JG contributed equally to this work.
Supported by National Key R&D Program of China No. 2017YFC0908900; National Key Basic Research Project, No. 2012CB517501; and National Natural Science Foundation of China, No. 81470840 and No. 81600464.
Institutional review board statement: The study was reviewed and approved by the Ethics Committee of Xinhua Hospital Affiliated to Shanghai Jiaotong University School of Medicine.
Institutional animal care and use committee statement: All procedures involving animals were reviewed and approved by the Institutional Animal Care and Use Committee of SHRM (SHRM-IACUC-001).
Conflict-of-interest statement: The authors declare that there is no conflict of interest related to this study.
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: Jian-Gao Fan, PhD, Professor, Center for Fatty Liver, Department of Gastroenterology, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, 1665 Kong Jiang Road, Shanghai 200092, China. fanjiangao@xinhuamed.com.cn
Telephone: +86-21-25077340
Received: August 24, 2017
Peer-review started: August 25, 2017
First decision: October 11, 2017
Revised: October 16, 2017
Accepted: October 27, 2017
Article in press: October 27, 2017
Published online: December 14, 2017
Processing time: 110 Days and 0.2 Hours
Abstract
AIM

To evaluate the levels of miR-192-5p in non-alcoholic fatty liver disease (NAFLD) models and demonstrate the role of miR-192-5p in lipid accumulation.

METHODS

Thirty Sprague Dawley rats were randomly divided into three groups, which were given a standard diet, a high-fat diet (HFD), and an HFD with injection of liraglutide. At the end of 16 weeks, hepatic miR-192-5p and stearoyl-CoA desaturase 1 (SCD-1) levels were measured. MiR-192-5p mimic and inhibitor and SCD-1 siRNA were transfected into Huh7 cells exposed to palmitic acid (PA). Lipid accumulation was evaluated by oil red O staining and triglyceride assays. Direct interaction was validated by dual-luciferase reporter gene assays.

RESULTS

The HFD rats showed a 0.46-fold decrease and a 3.5-fold increase in hepatic miR-192-5p and SCD-1 protein levels compared with controls, respectively, which could be reversed after disease remission by liraglutide injection (P < 0.01). The Huh7 cells exposed to PA also showed down-regulation and up-regulation of miR-192-5p and SCD-1 protein levels, respectively (P < 0.01). Transfection with miR-192-5p mimic and inhibitor in Huh7 cells induced dramatic repression and promotion of SCD-1 protein levels, respectively (P < 0.01). Luciferase activity was suppressed and enhanced by miR-192-5p mimic and inhibitor, respectively, in wild-type SCD-1 (P < 0.01) but not in mutant SCD-1. MiR-192-5p overexpression reduced lipid accumulation significantly in PA-treated Huh7 cells, and SCD-1 siRNA transfection abrogated the lipid deposition aggravated by miR-192-5p inhibitor (P < 0.01).

CONCLUSION

This study demonstrates that miR-192-5p has a negative regulatory role in lipid synthesis, which is mediated through its direct regulation of SCD-1.

Keywords: miR-192-5p; Stearoyl-CoA desaturase 1; High fat diet; Lipid synthesis; Non-alcoholic fatty liver disease

Core tip: Hepatic miR-192-5p levels decreased in non-alcoholic steatohepatitis rat models fed a high-fat diet and the decrease could be reversed after disease remission by liraglutide therapy. miR-192-5p showed a direct interaction with stearoyl-CoA desaturase 1 (SCD-1). miR-192-5p overexpression significantly alleviated lipid accumulation in Huh7 cells exposed to PA, and SCD-1 siRNA abrogated the lipid deposition aggravated by miR-192-5p inhibitor. Our study provides evidence that miR-192-5p participates in lipid synthesis in non-alcoholic fatty liver disease (NAFLD) through SCD-1 and suggests that the overexpression of miR-192-5p may represent a promising treatment for NAFLD.