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Characterization of the molecular mechanisms by which TSC1 deletion in adipocytes increases oxidative metabolism and UCP1 content in white adipose tissue

Grant number: 17/17403-1
Support type:Scholarships in Brazil - Scientific Initiation
Effective date (Start): January 01, 2018
Effective date (End): June 30, 2020
Field of knowledge:Biological Sciences - Physiology - Physiology of Organs and Systems
Principal Investigator:William Tadeu Lara Festuccia
Grantee:Thayna dos Santos Vieira
Home 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

The exponential increase in obesity worldwide is an alarming problem as it increases the chances of developing other diseases associated with excessive adipose mass, such as Type II diabetes and insulin resistance. Currently in Brazil, about half of the population is overweight, progressing to a possible obesity. Therefore, a deeper understanding of the molecular mechanisms that determine adiposity is of major importance to develop new more effective strategies to treat obesity. In this sense, recent studies from our laboratory have shown that constitutive activation of mTOR complex 1 (mechanistic target of rapamycin, mTORC1) induced by the deletion of Tsc1 exclusively in adipocytes increases mitochondrial content and oxidative metabolism (oxygen consumption and fatty acid oxidation) in both visceral and subcutaneous fat, as well as, uncoupling protein 1 content in visceral fat. Herein, we will investigate how constitutive activation of mTORC1 promotes those phenotype. For this, we will test 2 hypotheses: 1) that the increase in mitochondrial content and oxidative metabolism induced by Tsc1 deletion result from the increased rates of protein synthesis in adipocytes induced by constitutive mTORC1 activation; 2) that the increased in visceral fat UCP1 content is mediated by an increase in transcriptional activities of PPAR±, PPARg, ER± or ERR±. (AU)