Measurement of different hepatic lipid species of liver-specific estrogen receptor alpha knockout mice

• Grant number: 22/07508-9
• Support Opportunities: Scholarships abroad - Research Internship - Master's degree
• Start date: October 31, 2022
• End date: February 28, 2023
• Field of knowledge: Biological Sciences - Physiology - General Physiology
• Principal Investigator: João Paulo Gabriel Camporez
• Grantee: Felipe Garcia da Silva Sucupira
• Supervisor: Gerald Shulman
• Host Institution: Faculdade de Medicina de Ribeirão Preto (FMRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
• Institution abroad: Yale School of Medicine (YSM), United States
• Associated to the scholarship: 21/02638-9 - Impact of estrogen receptor alpha on non-alcoholic fatty liver disease and liver energy metabolism, BP.MS

Abstract

Lifestyle and increased consumption of a high-fat diet largely contribute 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 lipid accumulation, mitochondrial dysfunction, as well as inflammation and endoplasmic reticulum stress. One of the consequences of this high-fat lifestyle and diet is Non-Alcoholic Fatty Liver Disease (NAFLD), which affects about 30% of adults and up to 10% of children in developed countries. In recent decades, data from clinical and experimental studies have shown that estradiol makes an essential contribution to glycemic homeostasis. In fact, reduced estrogen concentration during menopause is associated with increased visceral fat and, in turn, metabolic diseases such as insulin resistance, T2DM, and cardiovascular disease. Since the liver is a central organ in the development of DM2, the general objective of this project is to study the impact of the absence of estrogen receptor alpha (ER±) on hepatic lipid metabolism and on the transformation of fatty acids from the diet into triacylglycerols and their impact on insulin resistance, using animals with ER± deletion specifically in the liver (Cre-Lox system). (AU)