Effects of lipids on insulin signaling in hepatocytes: impacts on mitochondrial ROS and nitric oxide generation

• Grant number: 15/04232-9
• Support Opportunities: Scholarships abroad - Research Internship - Scientific Initiation
• Start date: July 06, 2015
• End date: November 05, 2015
• Field of knowledge: Biological Sciences - Biochemistry - Metabolism and Bioenergetics
• Principal Investigator: Alicia Juliana Kowaltowski
• Grantee: Pâmela Aiako Hypólito Brito Kakimoto
• Supervisor: André Marette
• Host Institution: Instituto de Química (IQ). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Institution abroad: Université Laval, Canada
• Associated to the scholarship: 13/03556-0 - Effect of high fat diet on hepatocytes: impacts on ROS generation, BP.IC

Abstract

The increase in intracellular oxidant production due to nutrient load obtained in the diet has been directly linked to the development of metabolic diseases such as nonalcoholic fatty liver disease (NAFLD) and type 2 diabetes. Mitochondria are important sources in the generation of oxidants; the energy imbalance generated by increased caloric intake without the consideration of physiological energy demand can lead to an accumulation of reduced intermediates and the generation of reactive oxygen species (ROS). Both ROS and reactive nitrogen species (RNS) may impair insulin signaling at the receptor level and downstream, leading to insulin resistance and the development of metabolic diseases. Besides the well-known markers of oxidative damage, many metabolic and signaling enzymes are susceptible to nitrosative modification, i.e cysteine S-nitrosylation and tyrosine nitration, as posttranslational modifications. Since there is strong evidence of redox participation in insulin resistance development, we wish to evaluate the effects of fatty acid overload in the insulin signaling of hepatocytes, correlating bioenergetic changes and redox signaling. (AU)