Basic Study
Copyright ©The Author(s) 2020. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Mar 14, 2020; 26(10): 1029-1041
Published online Mar 14, 2020. doi: 10.3748/wjg.v26.i10.1029
Mesencephalic astrocyte-derived neurotrophic factor ameliorates steatosis in HepG2 cells by regulating hepatic lipid metabolism
Miao He, Cong Wang, Xiao-Hong Long, Jia-Jia Peng, Dong-Fang Liu, Gang-Yi Yang, Michael D Jensen, Li-Li Zhang
Miao He, Cong Wang, Xiao-Hong Long, Jia-Jia Peng, Dong-Fang Liu, Gang-Yi Yang, Li-Li Zhang, Department of Endocrinology, the Second Affiliated Hospital, Chongqing Medical University, Chongqing 400010, China
Michael D Jensen, Endocrine Research Unit, Mayo Clinic, Rochester, MN 55905, United States
Author contributions: He M and Wang C performed the majority of the experiments and contributed to the analysis of the data and the drafting of the manuscript; Long XH and Peng JJ contributed to the analysis of the data; Liu DF and Yang GY revised and approved the final version of the manuscript; Zhang LL contributed to the study design, the drafting of the manuscript, and critical discussion and approved the final version of the manuscript; Jensen MD revised, discussed, and approved the final version of the manuscript.
Supported by National Natural Science Foundation of China, No. 81300702 and No. 81501199; Natural Science Foundation Project of Chongqing CSTC, No. cstc2018jcyjAX0210 and No. cstc2017jcyjAX0016; and the Kuanren Talents Program of the Second Affiliated Hospital of Chongqing Medical University.
Institutional animal care and use committee statement: This study protocol was reviewed and approved by the Animal Care and Use Ethics Committee of Chongqing Medical University, Chongqing, China (protocol No. 2019-48). All animal experiments conformed to the accepted principles for the care and use of laboratory animals (license No. SYXK 2018-0003).
Conflict-of-interest statement: All the authors have no conflicts of interest related to the manuscript.
Data sharing statement: No additional data are available.
ARRIVE guidelines statement: The authors have read the ARRIVE guidelines, and the manuscript was prepared and revised according to the ARRIVE guidelines.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (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:
Corresponding author: Li-Li Zhang, MD, PhD, Associate Professor, Doctor, Postdoc, Research Fellow, Department of Endocrinology, the Second Affiliated Hospital, Chongqing Medical University, 74 Linjiang Road, Yuzhong District, Chongqing 400010, China.
Received: November 21, 2019
Peer-review started: November 21, 2019
First decision: January 7, 2020
Revised: February 15, 2020
Accepted: February 21, 2020
Article in press: February 21, 2020
Published online: March 14, 2020
Research background

Nonalcoholic fatty liver disease (NAFLD) is a global metabolism-associated liver disease. Hepatic steatosis, inflammation, and insulin resistance are the primary pathologic changes of NAFLD. Although NAFLD has become a serious threat to human public health, its pathogenic mechanisms are largely unknown.

Research motivation

Mesencephalic astrocyte-derived neurotrophic factor (MANF) is a newly discovered conserved neurotrophic factor. Recent studies found that MANF is involved in diabetes, obesity, and metabolic homeostasis. However, much remains to be discovered about its function in hepatic lipid metabolism; thus, we detected whether MANF could regulate hepatic metabolism.

Research objectives

This study aimed to detect MANF expression in both in vivo and in vitro NAFLD models and explore the role of MANF in hepatic lipid metabolism.

Research methods

HepG2 cells treated with free fatty acids and ob/ob mice were used as NAFLD models. Liver tissues collected from WT and ob/ob mice were used to detect MANF expression. Cells were treated with free fatty acids for different durations. Moreover, we established overexpression and knockdown cell models with lentiviruses to interfere with MANF expression levels in order to observe whether MANF influences hepatic steatosis.

Research results

Hepatic MANF expression was obviously decreased in ob/ob mice compared with wild type mice. The MANF level was elevated temporarily and gradually decreased in HepG2 cells as the duration of treatment with high free fatty acids increased. MANF deficiency accelerated lipogenesis and aggravated HepG2 cell steatosis, while MANF overexpression inhibited lipogenesis and rescued HepG2 cells from free fatty acids-induced steatosis.

Research conclusions

MANF alleviated lipid deposition and suppressed lipogenes, showing a potential protective role in NAFLD.

Research perspectives

MANF may be a potential therapeutic target in hepatic steatosis processes.