Involvement of autophagy in the metabolic and inflammatory changes induced by mTORC1 inactivation in adipocytes

• Grant number: 16/05406-3
• Support Opportunities: Scholarships in Brazil - Master
• Start date: July 01, 2016
• End date: September 30, 2017
• Field of knowledge: Biological Sciences - Physiology
• Principal Investigator: William Tadeu Lara Festuccia
• Grantee: Milene Ortiz Silva
• Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Associated research grant: 15/19530-5 - Involvement of the nutrient sensor mTOR in the development of obesity associated chronic metabolic diseases, AP.TEM

Abstract

In this proposal, we will test the hypothesis that autophagy is an important mediator of the metabolic, morphologic and inflammatory changes in adipose tissue found upon obesity (mTORC1 gain of function) or inactivation of mTORC1 (loss of function) in adipocytes. For this, we will conduct two different protocols: (1) C57BL6J fed with a chow or high fat diet will be treated or not with autophagy inhibitor chloroquine for 8 weeks with the goal of assessing the interaction between mTORC1 and autophagy in the context of obesity. (2) Mice wild type (WT) or with Raptor knockout in adipocytes (Raptor KO) will be fed a high fat diet and treated or not with chloroquine in order to evaluate the contribution of autophagy in the phenotypes induced mTORC1 deficiency. We will evaluate weight gain, food intake, energy expenditure, body fat, adipocytes diameter and number, insulin and glucose tolerance, uptake and metabolism of glucose and fatty acids mitochondrial content and function, intracellular insulin and inflammatory singling, leukocytes recruitment and phenotype and adipose tissue and liver inflammation. Multifactorial ANOVA will be used to analyze the results (GraphPad Prism 6.0). Data will be expressed as mean +/- SEM, significance level of p <0.05.