Spleen influence over the macrophage infiltration and insulin resistance in diet-induced obesity

• Grant number: 11/23940-3
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• Start date: June 01, 2012
• End date: April 30, 2013
• Field of knowledge: Health Sciences - Medicine - Medical Clinics
• Principal Investigator: Mario Jose Abdalla Saad
• Grantee: Bruno de Melo Carvalho
• Host Institution: Faculdade de Ciências Médicas (FCM). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil

Abstract

Over the last decades, obesity acquired epidemics proportions over the world, mainly in developed countries, but also in under development nations like Brazil. This disease is characterized by an chronic subclinical inflammation with elevated circulating levels of proinflammatory cytokines, such as TNF-alpha and IL-6. Other marked feature of obesity is the insulin target tissues immune cells infiltration, specially liver and adipose tissue, mainly represented by macrophages, which works towards inflammation expansion and maintenance and insulin resistance induction. Recent studies show that the spleen monocytes are stimulated to migrate and differentiate in macrophages on inflammatory sites by angiotensin II dependent mechanisms. Additionally, preliminary results indicate that novel proteins could be involved on cell infiltration and insulin resistance induction, and that the spleen is a major source of these elements. This way, we have as objectives: To investigate the effect of splenectomy on 1, 2 or 3 angiotensin converting enzyme (ACE) copies on diet induced insulin resistance and lipolysis induced monocyte migration, and also, to characterize their splenic monocytes and macrophages, as well as, obese mice splenic cells; To investigate splenectomized obese mice serum proteins expression compared to its control and lean counterparts, and the spleen protein expression profile in lean and obese mice by proteomics approaches; To investigate the activity of GMF-gamma protein on obesity induced insulin resistance and lipolysis induced monocyte migration, as well as this protein inhibition in both conditions.