Hepatocyte glutathione peroxidase-1 deficiency improves hepatic glucose metabolism and decreases steatohepatitis in mice

Abstract

Aims/hypothesis: In obesity oxidative stress is thought to contribute to the development of insulin resistance, non-alcoholic fatty liver disease and the progression to non-alcoholic steatohepatitis. Our aim was to examine the precise contributions of hepatocyte-derived H2O2 to liver pathophysiology. Methods: Glutathione peroxidase (GPX) 1 is an antioxidant enzyme that is abundant in the liver and converts H2O2 to water. We generated Gpx1lox/lox mice to conditionally delete Gpx1 in hepatocytes (Alb-Cre;Gpx1lox/lox) and characterised mice fed chow, high-fat or choline-deficient amino-acid-defined (CDAA) diets. Results: Chow-fed Alb-Cre;Gpx1lox/lox mice did not exhibit any alterations in body ..