High-fat-fed obese glutathione peroxidase 1-deficient mice exhibit defective insulin secretion but protection from hepatic steatosis and liver damage

Abstract

Aims: Reactive oxygen species (ROS) such as H2O2 can promote signaling through the inactivation of protein tyrosine phosphatases (PTPs). However, in obesity, the generation of ROS exceeds the antioxidant reserve and can contribute to the promotion of insulin resistance. Glutathione peroxidase 1 (Gpx1) is an antioxidant enzyme that eliminates H2O 2. Here, we have used Gpx1-/- mice to assess the impact of oxidative stress on glucose homeostasis in the context of obesity. Results: Gpx1-/- mice fed an obesogenic high-fat diet for 12 weeks exhibited systemic oxidative stress and hyperglycemia, but had unaltered whole-body insulin sensitivity, improved hepatic insulin signaling, and decreased whol..