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

Grant number: 15/04232-9
Support type:Scholarships abroad - Research Internship - Scientific Initiation
Effective date (Start): July 06, 2015
Effective date (End): November 05, 2015
Field of knowledge:Biological Sciences - Biochemistry
Principal Investigator:Alicia Juliana Kowaltowski
Grantee:Pâmela Aiako Hypólito Brito Kakimoto
Supervisor abroad: André Marette
Home Institution: Instituto de Química (IQ). Universidade de São Paulo (USP). São Paulo , SP, Brazil
Local de pesquisa : 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)