Hepatocyte-specific expression of human carboxylesterase 2 attenuates non-alcoholic steatohepatitis in mice.

Title

Hepatocyte-specific expression of human carboxylesterase 2 attenuates non-alcoholic steatohepatitis in mice.

Creator

Xu Y; Pan X; Hu S; Zhu Y; Cassim BF; Li Y; Yin L; Zhang Y

Publisher

American Journal of Physiology-Gastrointestinal and Liver Physiology

Date

2020
2020-12-16

Description

Human carboxylesterase 2 (CES2) has triacylglycerol hydrolase (TGH) activities and plays an important role in lipolysis. In this study, we aim to determine the role of human CES2 in the progression or reversal of steatohepatitis in diet-induced or genetically obese mice. High-fat/high-cholesterol/high-fructose (HFCF) diet-fed C57BL/6 mice or db/db mice were i.v. injected with an adeno-associated virus expressing human CES2 under the control of an albumin promoter. Human CES2 protected against HFCF diet-induced non-alcoholic fatty liver disease (NAFLD) in C57BL/6J mice and reversed steatohepatitis in db/db mice. Human CES2 also improved glucose tolerance and insulin sensitivity. Mechanistically, human CES2 reduced hepatic triglyceride and free fatty acid levels by inducing lipolysis and fatty acid oxidation and inhibiting lipogenesis via suppression of sterol regulatory element-binding protein 1. Furthermore, human CES2 overexpression improved mitochondrial respiration and glycolytic function, and inhibited gluconeogenesis, lipid peroxidation, apoptosis and inflammation. Our data suggest that hepatocyte-specific expression of human CES2 prevents and reverses steatohepatitis. Targeting hepatic CES2 may be an attractive strategy for treatment of NAFLD.

Subject

CES2; Fatty acid oxidation; Lipolysis; Lipotoxicity; Steatohepatitis

Rights

Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).

Format

journalArticle

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ISSN

1522-1547 0193-1857

NEOMED College

NEOMED College of Medicine

NEOMED Department

Department of Integrative Medical Sciences
NEOMED Postdoc Publications

Update Year & Number

January 2021 List

Citation

Xu Y; Pan X; Hu S; Zhu Y; Cassim BF; Li Y; Yin L; Zhang Y, “Hepatocyte-specific expression of human carboxylesterase 2 attenuates non-alcoholic steatohepatitis in mice.,” NEOMED Bibliography Database, accessed May 22, 2022, https://neomed.omeka.net/items/show/11508.

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