mTORC1 is a major regulator of adipose tissue BCAA metabolism and lipolysis in visceral, subcutaneous and brown adipose tissue of mice through a mechanism that involves PPARgamma activation

• Grant number: 20/10215-8
• Support Opportunities: Scholarships in Brazil - Master
• Start date: December 01, 2020
• End date: December 31, 2022
• Field of knowledge: Biological Sciences - Physiology - Physiology of Organs and Systems
• Principal Investigator: William Tadeu Lara Festuccia
• Grantee: Thayna dos Santos Vieira
• 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

Preliminary results obtained at undergraduated scientific training suggest that constitutive mTORC1 activation induced by Tsc1 deletion in adipocytes increases adipose tissue BCAA oxidation and lipolysis. Considering these findings, in this master proposal, we will test the hypothesis that mTORC1 is a major regulator of adipose tissue BCAAmetabolismo and lipolysis in visceral, subcutaneous and brown adipose tissue of mice through a mechanism that involves PPAR³ activation. To test this hypothesis, we will conduct 2 protocols. In the first, mice bearing Tsc1 deletion in adipocytes and littermatecontrols will be fed either a chow or a high-fat diet (60% of calories from fat) for 8 weeks and evaluated for body weight, food intake, glucose homoestasis (GTT and ITT), serum levels of insulin, glucose, BCAA, free fatty acids and glycerol, and visceral, subcutaneous and brown adipose tissue BCAA oxidation and incorporation into triacylglycerol, basal and stimulated lipolysis, and mRNA (qPCR) and/or protein (Western blotting) contents of proteins involvedin BCAA metabolism, lipolysis as well as PPARgamma1 e PPARgamma2. In the second protocol, mice bearing Tsc1 deletion in adipocytes and littermate controls fed with either a chow ou a highfat diet (60% of calories from fat) for 8 weeks will be treated daily for 14 days with intraperitoneal injections of either vehicle (PBS, 10% DMSO) or the PPARgamma antagonista BADGE (50 mg/ kg weight/ day; Sigma) and evaluated for the same variables listed inprotocol 1. (AU)

Scientific publications

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

PEIXOTO, ALBERT S.; MORENO, MAYARA F.; CASTRO, ERIQUE; PERANDINI, LUIZ A.; BELCHIOR, THIAGO; OLIVEIRA, TIAGO E.; VIEIRA, THAYNA S.; GILIO, GUSTAVO R.; TOMAZELLI, CAROLINE A.; LEONARDI, BIANCA F.; et al. Hepatocellular carcinoma induced by hepatocyte Pten deletion reduces BAT UCP-1 and thermogenic capacity in mice, despite increasing serum FGF-21 and iWAT browning. JOURNAL OF PHYSIOLOGY AND BIOCHEMISTRY, v. N/A, p. 13-pg., 2023-07-05. (17/12260-8, 21/14419-0, 19/17660-0, 20/10215-8, 15/19530-5, 20/04159-8, 19/04271-5, 18/03418-0, 22/02123-1, 17/17582-3, 17/23040-9, 19/01763-4, 15/22983-1, 20/09399-7)