Involvement of adipocytes mTOR complexes 1 and 2 in the morphological, metabolic and secretory changes induced by pharmacological PPARgamma activation

• Grant number: 15/13508-8
• Support Opportunities: Scholarships in Brazil - Doctorate
• Start date: July 01, 2016
• End date: June 30, 2019
• Field of knowledge: Biological Sciences - Physiology - Physiology of Organs and Systems
• Principal Investigator: William Tadeu Lara Festuccia
• Grantee: Maynara Lucca Andrade
• 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
• Associated scholarship(s): 17/21150-1 - Genomic and Epigenomic analysis of insulin action, BE.EP.DR

Abstract

Thiazolidinediones (TZDs), synthetic ligands for the nuclear receptor PPAR³, have been largely used in the treatment of metabolic diseases such as insulin resistance, dyslipidemias and metabolic syndrome. These drugs were shown to improve glucose homeostasis by promoting fat redistribution from visceral to subcutaneous depots, adiponectin secretion and by reducing lipemia, lipotoxicity, and adipose tissue inflammation. We have recently found that rats treated with rosiglitazone (one kind of TZD) feature an increased activity of mTOR complexes 1 and 2 in adipocytes, such complexes that were shown to play key roles in regulation of lipid metabolism and adiposity. Therefore, this study aims to elucidate the involvement of adipocyte mTOR complexes 1 and 2 in the morphological, secretory and metabolic changes in white and brown adipose tissue induced by pharmacological PPAR³ activation. More specifically, it will be investigated: 1) the involvement of mTOR complexes 1 and 2 in fat redistribution from visceral to subcutaneous depots and increase of brown adipose tissue mass induced by pharmacological PPAR³ activation; 2) the involvement of mTOR complexes 1 and 2 in mitochondrial biogenesis and increase of UCP1 content in white and brown adipose tissue induced by pharmacological PPAR³ activation; 3) the involvement of mTOR complexes 1 and 2 in endocrine function alterations induced by pharmacological PPAR³ activation.

Scientific publications

(6)

(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)

ANDRADE, MAYNARA L.; GILIO, GUSTAVO R.; PERANDINI, LUIZ A.; PEIXOTO, ALBERT S.; MORENO, MAYARA F.; CASTRO, ERIQUE; OLIVEIRA, TIAGO E.; VIEIRA, THAYNA S.; ORTIZ-SILVA, MILENE; THOMAZELLI, CAROLINE A.; et al. PAR gamma-induced upregulation of subcutaneous fat adiponectin secretion, glyceroneogenesis and BCAA oxidation requires mTORC1 activit. BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR AND CELL BIOLOGY OF LIPIDS, v. 1866, n. 8, AUG 2021. (15/19530-5, 17/17582-3, 13/07937-8, 19/01763-4, 17/12260-8, 15/22983-1, 16/23169-9, 19/04271-5, 15/13508-8, 18/11156-5, 19/17660-0, 17/23040-9, 17/17403-1)

BLANCHARD, PIERRE-GILLES; MOREIRA, RAFAEL J.; CASTRO, ERIQUE; CARON, ALEXANDRE; COTE, MARIE; ANDRADE, MAYNARA L.; OLIVEIRA, TIAGO E.; ORTIZ-SILVA, MILENE; PEIXOTO, ALBERT S.; DIAS, FRANCE ANNE; et al. PPAR gamma is a major regulator of branched-chain amino acid blood levels and catabolism in white and brown adipose tissues. METABOLISM-CLINICAL AND EXPERIMENTAL, v. 89, p. 27-38, DEC 2018. (15/19530-5, 16/07062-0, 17/12260-8, 16/23169-9, 15/13508-8)

OLIVEIRA, TIAGO E.; CASTRO, ERIQUE; BELCHIOR, THIAGO; ANDRADE, MAYNARA L.; CHAVES-FILHO, ADRIANO B.; PEIXOTO, ALBERT S.; MORENO, MAYARA F.; ORTIZ-SILVA, MILENE; MOREIRA, RAFAEL J.; INAGUE, ALEX; et al. Fish Oil Protects Wild Type and Uncoupling Protein 1-Deficient Mice from Obesity and Glucose Intolerance by Increasing Energy Expenditure. MOLECULAR NUTRITION & FOOD RESEARCH, v. 63, n. 7, APR 2019. (15/19530-5, 17/17582-3, 16/07062-0, 17/12260-8, 15/22983-1, 16/23169-9, 15/13508-8, 18/11156-5, 17/23040-9)

CHIMIN, PATRICIA; ANDRADE, MAYNARA L.; BELCHIOR, THIAGO; PASCHOAL, VIVIAN A.; MAGDALON, JULIANA; YAMASHITA, ALEX S.; CASTRO, ERIQUE; CASTOLDI, ANGELA; CHAVES-FILHO, ADRIANO B.; YOSHINAGA, MARCOS Y.; et al. Adipocyte mTORC1 deficiency promotes adipose tissue inflammation and NLRP3 inflammasome activation via oxidative stress and de novo ceramide synthesis. Journal of Lipid Research, v. 58, n. 9, p. 1797-1807, SEP 2017. (12/25317-4, 15/19530-5, 12/02270-2, 15/13508-8, 09/15354-7)

ANDRADE, MAYNARA L.; GILIO, GUSTAVO R.; PERANDINI, LUIZ A.; PEIXOTO, ALBERT S.; MORENO, MAYARA F.; CASTRO, ERIQUE; OLIVEIRA, TIAGO E.; VIEIRA, THAYNA S.; ORTIZ-SILVA, MILENE; THOMAZELLI, CAROLINE A.; et al. PPAR gamma-induced upregulation of subcutaneous fat adiponectin secretion, glyceroneogenesis and BCAA oxidation requires mTORC1 activity. BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR AND CELL BIOLOGY OF LIPIDS, v. 1866, n. 8, p. 11-pg., 2021-05-19. (19/17660-0, 16/23169-9, 17/23040-9, 15/22983-1, 17/17403-1, 19/04271-5, 13/07937-8, 17/17582-3, 15/19530-5, 17/12260-8, 18/11156-5, 15/13508-8, 19/01763-4)

CASTRO, ERIQUE; VIEIRA, THAYNA S.; OLIVEIRA, TIAGO E.; ORTIZ-SILVA, MILENE; ANDRADE, MAYNARA L.; TOMAZELLI, CAROLINE A.; PEIXOTO, ALBERT S.; SOBRINHO, CLEYTON R.; MORENO, MAYARA F.; GILIO, GUSTAVO R.; et al. Adipocyte-specific mTORC2 deficiency impairs BAT and iWAT thermogenic capacity without affecting glucose uptake and energy expenditure in cold-acclimated mice. AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM, v. 321, n. 5, p. E592-E605, NOV 2021. (16/23169-9, 19/25943-1, 17/23040-9, 15/13508-8, 17/17582-3, 18/03418-0, 17/17403-1, 17/12260-8, 19/01763-4, 19/17660-0, 15/19530-5, 20/09399-7, 19/04271-5, 12/25317-4)

Academic Publications

(References retrieved automatically from State of São Paulo Research Institutions)

ANDRADE, Maynara Lucca. mTORC1 is an important mediator of the increase in serum adiponectin and BCAA metabolism in adipose tissue induced by rosiglitazone.. 2019. Doctoral Thesis - Universidade de São Paulo (USP). Instituto de Ciências Biomédicas (ICB/SDI) São Paulo.