ANALYSIS OF CHOLESTEROL MASS AND THEIR EXCRETION PRODUCTS IN MICE LDLR-DEFICIENT, APOE-DEFICIENT AND WILD (CONTROLS) FEED WITH FREE CHOLESTEROL DIET

• Grant number: 15/17566-2
• Support Opportunities: Regular Research Grants
• Duration: March 01, 2016 - August 31, 2018
• Field of knowledge: Health Sciences - Medicine - Medical Clinics
• Principal Investigator: Valéria Sutti Nunes
• Grantee: Valéria Sutti Nunes
• Host Institution: Faculdade de Medicina (FM). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Associated researchers: Eder Carlos Rocha Quintão ; Patricia Miralda Cazita ; Sergio Catanozi

Abstract

Familial hypercholesterolemia (FH) is an autosomal dominant genetic disorder characterized by very elevated LDL-c (low density lipoprotein cholesterol) plasma concentration and by increased risk of premature coronary artery disease which is caused by defects of the LDL receptor in hepatocytes and in cells such as fibroblasts that prevent the removal of LDL from the circulation. LDL particles remaining longer time in the circulation are more prone to oxidation and other chemical transformations bringing on increased uptake of modified LDL by macrophages, triggering atherosclerosis. There are no evidences for cholesterol synthesis being altered in FH cases as compares to normocholesterolemic individuals. In the population at large hypercholesterolemia has in part been related to dietary cholesterol absorption, but FH might be ascribed to changes in body cholesterol production or excretion. Genetic apoE-deficient and LDLR-deficient mice are well established models in the study hypercholesterolemia and atherosclerosis, as these mice develop spontaneous hypercholesterolemia and atherosclerosis in the chow diet. The objective of this study is to measure the cholesterol mass in all tissues and fecal and urinary excretion of neutral and acidic sterols in LDLR-deficient mice, in apoE-deficient and in wild type (controls) submitted to a cholesterol-free diet. In these models, fecal steroids excreted and the cholesterol body content represent the body cholesterol production. Analyses of the cholesterol content and its excreted metabolites will disclose if the cholesterol production differs in these mice models. (AU)