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

Title

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

Creator

Xu Y;Pan X; Shuwei H;Zhu Y; Bawa FC;Li Y; Yin L; Zhang Y

Publisher

American Journal Of Physiology: Gastrointestinal & Liver Physiology

Date

2021
2021-02-01

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 intravenously injected with an adeno-associated virus expressing human CES2 under the control of an albumin promoter. Human CES2 protected against HFCF diet-induced nonalcoholic 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 (T) and free fatty acid (FFA) 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.

Rights

Copyright © 2021 the American Physiological Society

Format

Journal Article

NEOMED College

NEOMED College of Medicine

NEOMED Department

Department of Integrative Medical Sciences

Update Year & Number

Jan to Aug list 2021

Citation

Xu Y;Pan X; Shuwei H;Zhu Y; Bawa FC;Li Y; Yin L; Zhang Y, “Hepatocyte-specific expression of human carboxylesterase 2 attenuates nonalcoholic steatohepatitis in mice.,” NEOMED Bibliography Database, accessed June 29, 2022, https://neomed.omeka.net/items/show/11855.

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