Characterization of adipose tissue inflammation in LDL receptor knockout mice

• Grant number: 11/23118-1
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Effective date (Start): February 01, 2012
• Effective date (End): April 30, 2013
• Field of knowledge: Biological Sciences - Physiology - Physiology of Organs and Systems
• Principal Investigator: Thais Martins de Lima Salgado
• Grantee: Iryna Hirata Prist
• Host Institution: Faculdade de Medicina (FM). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

Obesity and atherosclerosis are diseases found in several patients simultaneously. The literature suggests that in addition to dyslipidemia, chronic inflammation observed in obesity is related to the activation of macrophages in the vessels and the development of atherosclerosis. However no studies investigating whether the metabolic changes (storage and hydrolysis of triacylglycerol and cholesterol) from adipose tissue during development of obesity are a cause or consequence of the inflammation observed in this tissue, which contributes to the inflammation observed in obese individuals. In this project we propose to characterize inflammation and metabolic changes in adipose tissue of mice deficient for the LDL receptor, a model that develops atherosclerosis when subjected to a diet rich in saturated fat and cholesterol. Although the vessel inflammation in this model is well characterized, only the work of Subramanian and colleagues (2008) showed that the adipose tissue of these animals is inflamed. However, inflammation of adipose tissue was analyzed by quantifying the tissue macrophages, and after a very long period of diet (24 weeks). Our hypothesis is that the hypercholesterolemic diet causes early changes in the ability of adipose tissue to store triacylglycerol and cholesterol, leading to the recruitment of macrophages into the tissue. These cells in turn are activated, increasing the secretion of cytokines and pro-inflammatory proteins by fat tissue, stimulating lipolysis and increasing plasma concentrations of lipids. Thus, changes in adipose tissue contribute to the development of atherosclerotic plaques in animals, making it a potential therapeutic target for treating atherosclerosis.(AU)