Development and characterization of a new model of Non-Alcoholic Steatohepatitis in mice

• Grant number: 22/05445-0
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: December 01, 2022
• End date: November 30, 2023
• Field of knowledge: Biological Sciences - Physiology - Physiology of Organs and Systems
• Principal Investigator: João Paulo Gabriel Camporez
• Grantee: Carolina Coelho Barretto Dias
• Host Institution: Faculdade de Medicina de Ribeirão Preto (FMRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil

Abstract

Lifestyle and increased consumption of high-fat diets contribute greatly to the development of obesity, insulin resistance, type 2 diabetes (DM2) and cardiovascular disease. Several mechanisms are currently considered to cause insulin resistance, such as abnormal lipid metabolism and ectopic accumulation, mitochondrial dysfunction, inflammation and endoplasmic reticulum stress. One consequence of Western lifestyle and high fat diet is Non-Alcoholic Fatty Liver Disease (NAFLD), which affects about 30% of adults and up to 10% of children in developed countries. The progression of NAFLD is its evolution to nonalcoholic steatohepatitis (NASH), which is characterized by macro and / or microvesicular steatosis, mixed lobular inflammatory infiltrate and heptocellular ballooning in the area of the centrolobular vein (zone III), Mallory fibrosis and corpuscles. Since the liver is an organ that regulates the carbohydrates and lipids metabolism, and the dysregulation in this metabolism can lead to hepatic steatosis and progress to inflammatory processes, several studies have proposed different models of nonalcoholic steatohepatitis to understand the mechanisms of this disease and develop future therapeutic targets. Therefore, the aim of this project is to propose a new model of NASH, which is developed in a shorter time, approximately in four weeks, in C57BL/6 mice fed a high-fat diet and treated with carbon tetrachloride (CCl4).