Basic Study
Copyright ©The Author(s) 2019. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Dec 7, 2019; 25(45): 6607-6618
Published online Dec 7, 2019. doi: 10.3748/wjg.v25.i45.6607
LB100 ameliorates nonalcoholic fatty liver disease via the AMPK/Sirt1 pathway
Xue-Yang Chen, Chang-Zhou Cai, Meng-Li Yu, Ze-Min Feng, Yu-Wei Zhang, Pei-Hao Liu, Hang Zeng, Chao-Hui Yu
Xue-Yang Chen, Chang-Zhou Cai, Meng-Li Yu, Ze-Min Feng, Yu-Wei Zhang, Pei-Hao Liu, Hang Zeng, Chao-Hui Yu, Department of Gastroenterology, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou 310003, Zhejiang Province, China.
Chao-Hui Yu, Clinical Research Center for Hepatobiliary and Pancreatic Diseases of Zhejiang Province, Hangzhou 310003, Zhejiang Province, China
Author contributions: Chen XY and Cai CZ designed and performed the study, conducted the statistical analysis and wrote the paper; Yu ML, Feng ZM, Zhang YW, Liu PH and Zeng H performed the study and provided guidance during revision; Yu CH supervised the study and provided consultation during the entire study.
Institutional animal care and use committee statement: All experiments were conducted with approval of the First Affiliated Hospital of Zhejiang University Institutional Animal Care and Use Committee.
Conflict-of-interest statement: Authors have no conflicts of interest to disclose.
Data sharing statement: No additional data are available.
ARRIVE guidelines statement: Authors have read the ARRIVE guidelines and prepared and revised the manuscript according to the ARRIVE guidelines.
Open-Access: This 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 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:
Corresponding author: Chao-Hui Yu, MD, PhD, Chief Doctor, Professor, Department of Gastroenterology, The First Affiliated Hospital, College of Medicine, Zhejiang University, 79 Qingchun Road, Hangzhou 310003, Zhejiang Province, China.
Telephone: +86-571-87236739 Fax: +86-571-87236739
Received: October 16, 2019
Peer-review started: October 16, 2019
First decision: November 4, 2019
Revised: November 10, 2019
Accepted: November 23, 2019
Article in press: November 24, 2019
Published online: December 7, 2019

It is well known that nonalcoholic fatty liver disease (NAFLD) is associated with insulin resistance (IR). LB100, a serine/threonine protein phosphatase 2A (PP2A) inhibitor, is closely related to IR. However, there is little data regarding its direct influence on NAFLD.


To elucidate the effect and underlying mechanism of LB100 in NAFLD.


After 10 wk of high fat diet (HFD) feeding, male C57BL/6 mice were injected intraperitoneally with vehicle or LB100 for an additional 6 wk (three times a week). The L02 cell line was treated with LB100 and free fatty acids (FFAs) for 24 h. Hematoxylin and eosin and oil red O staining were performed for histological examination. Western blot analysis was used to detect the protein expression of Sirtuin 1 (Sirt1), total and phosphorylated AMP-activated protein kinase α (AMPKα), and the proteins involved in lipogenesis and fatty acid oxidation. The mRNA levels were determined by qPCR. Pharmacological inhibition of AMPK was performed to further examine the exact mechanism of LB100 in NAFLD.


LB100 significantly ameliorated HFD-induced obesity, hepatic lipid accumulation and hepatic injury in mice. In addition, LB100 significantly downregulated the protein levels of acetyl-CoA carboxylase, sterol regulatory element-binding protein 1 and its lipogenesis target genes, including stearoyl-CoA desaturase-1 and fatty acid synthase, and upregulated the levels of proteins involved in fatty acid β-oxidation, such as peroxisome proliferator-activated receptor α (PPARα), peroxisome proliferator-activated receptor gamma coactivator-1α (PGC-1α), carnitine palmitoyltransferase 1α, acyl-CoA oxidase 1 and uncoupling protein 2, as well as the upstream mediators Sirt1 and AMPKα in the livers of HFD-fed mice. In vitro, LB100 alleviated FFA-induced lipid accumulation in L02 cells through the AMPK/Sirt1 signaling pathway. Further studies showed that the curative effect of LB100 on lipid accumulation was abolished by inhibiting AMPKα in L02 cells.


PP2A inhibition by LB100 significantly ameliorates hepatic steatosis by regulating hepatic lipogenesis and fatty acid oxidation via the AMPK/Sirt1 pathway. LB100 may be a potential therapeutic agent for NAFLD.

Keywords: LB100, Nonalcoholic fatty liver disease, Serine/threonine-protein phosphatase 2A, Lipid metabolism, AMP-activated protein kinase α, Sirtuin 1

Core tip: Nonalcoholic fatty liver disease (NAFLD) is one of the most common chronic liver diseases worldwide, which greatly increases the medical and economic burden. We aimed to investigate the effect and underlying mechanism of LB100 in lipid accumulation during NAFLD development in mice fed a high fat diet and L02 cells treated with free fatty acids. Our study provided, for the first time, in vivo and in vitro evidence that LB100 can effectively inhibit hepatic lipogenesis via the AMPK/Sirt1 pathway and could be a therapeutic strategy for NAFLD.