Involvement of the transcriptional corepressor NCoR in the development of high fat diet induced hepatic inflammation and insulin resistance

• Grant number: 14/04215-4
• Support Opportunities: Scholarships abroad - Research Internship - Doctorate
• Start date: August 01, 2014
• End date: July 31, 2015
• Field of knowledge: Biological Sciences - Physiology - General Physiology
• Principal Investigator: William Tadeu Lara Festuccia
• Grantee: Vivian Almeida Paschoal
• Supervisor: Jerrold M. Olefsky
• Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Institution abroad: University of California, San Diego (UC San Diego), United States
• Associated to the scholarship: 11/10783-7 - mTOR complex 1 involvement in the control of macrophage function in the chronic inflammatory response associated with obesity and insulin resistance, BP.DR

Abstract

Obesity and insulin resistance are associated with a higher incidence of many chronic metabolic diseases such as fatty liver, cirrhosis and hepatocellular carcinoma. Several studies indicate that the intake of a high-fat diet induces excessive accumulation of lipids in the liver, generating a local inflammatory process characterized by increased expression of pro-inflammatory mediators, activation of Kupffer cells and leukocyte recruitment, such factors that are implicated in the development of hepatic insulin resistance. NCoR is a nuclear corepressor that modulates the transcriptional activity of several nuclear receptors such as PPARgamma, PPARalpha, NFkB among others, which is directly involved in the regulation of the expression of several inflammatory genes. Thus, the main goal of this research proposal is to investigate the involvement of NCoR in the development of hepatic steatosis, inflammation and insulin resistance induced by high fat diet intake. To this end, mice with NCoR deficiency specifically in hepatocytes or macrophages fed with a balanced or high fat diet will be evaluated for glucose production (gluconeogenesis and glycogenolysis), lipid content and metabolism and inflammation (recruitment and phenotype of liver resident macrophages and content of inflammatory mediators). (AU)