title: Ces3/TGH Deficiency Attenuates Steatohepatitis.
abstract: Nonalcoholic fatty liver disease (NAFLD) is the most common form of chronic liver disease in developed countries. NAFLD describes a wide range of liver pathologies from simple steatosis to nonalcoholic steatohepatitis (NASH) and cirrhosis. NASH is distinguished from simple steatosis by inflammation, cell death and fibrosis. In this study we found that mice lacking triacylglycerol hydrolase (TGH, also known as carboxylesterase 3 or carboxylesterase 1d) are protected from high-fat diet (HFD) - induced hepatic steatosis via decreased lipogenesis, increased fatty acid oxidation and improved hepatic insulin sensitivity. To examine the effect of the loss of TGH function on the more severe NAFLD form NASH, we ablated Tgh expression in two independent NASH mouse models, Pemt(-/-) mice fed HFD and Ldlr(-/-) mice fed high-fat, high-cholesterol Western-type diet (WTD). TGH deficiency reduced liver inflammation, oxidative stress and fibrosis in Pemt(-/-) mice. TGH deficiency also decreased NASH in Ldlr(-/-) mice. Collectively, these findings indicate that TGH deficiency attenuated both simple hepatic steatosis and irreversible NASH.
authors.affiliation: Group on Molecular and Cell Biology of Lipids, University of Alberta, Edmonton, Alberta, Canada.|Department of Pediatrics, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, Alberta, Canada.
authors.forename: Jihong
authors.initials: J
authors.lastname: Lian
authors.affiliation: Group on Molecular and Cell Biology of Lipids, University of Alberta, Edmonton, Alberta, Canada.|Department of Pediatrics, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, Alberta, Canada.
authors.forename: Enhui
authors.initials: E
authors.lastname: Wei
authors.affiliation: Department of Biochemistry, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, Alberta, Canada.
authors.forename: Jody
authors.initials: J
authors.lastname: Groenendyk
authors.affiliation: Department of Medicine, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, Alberta, Canada.
authors.forename: Subhash K
authors.initials: SK
authors.lastname: Das
authors.affiliation: Group on Molecular and Cell Biology of Lipids, University of Alberta, Edmonton, Alberta, Canada.|Department of Biochemistry, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, Alberta, Canada.
authors.forename: Martin
authors.initials: M
authors.lastname: Hermansson
authors.affiliation: Group on Molecular and Cell Biology of Lipids, University of Alberta, Edmonton, Alberta, Canada.|Department of Pediatrics, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, Alberta, Canada.
authors.forename: Lena
authors.initials: L
authors.lastname: Li
authors.affiliation: Group on Molecular and Cell Biology of Lipids, University of Alberta, Edmonton, Alberta, Canada.|Department of Pediatrics, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, Alberta, Canada.
authors.forename: Russell
authors.initials: R
authors.lastname: Watts
authors.affiliation: Department of Pathology, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, Alberta, Canada.
authors.forename: Aducio
authors.initials: A
authors.lastname: Thiesen
authors.affiliation: Department of Medicine, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, Alberta, Canada.
authors.forename: Gavin Y
authors.initials: GY
authors.lastname: Oudit
authors.affiliation: Department of Biochemistry, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, Alberta, Canada.
authors.forename: Marek
authors.initials: M
authors.lastname: Michalak
authors.affiliation: Group on Molecular and Cell Biology of Lipids, University of Alberta, Edmonton, Alberta, Canada.|Department of Pediatrics, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, Alberta, Canada.|Department of Cell Biology, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, Alberta, Canada.
authors.forename: Richard
authors.initials: R
authors.lastname: Lehner