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.
Identifier
Rights
Copyright © 2021 the American Physiological Society
Format
Journal Article
URL Address
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 April 24, 2024, https://neomed.omeka.net/items/show/11855.