Involvement of mTORC1 and 2 and PPARgamma in the regulation of leukocyte profile, recruitment and activation of brown adipose tissue and beige adipocytes induced by cold exposure

• Grant number: 16/23169-9
• Support Opportunities: Scholarships in Brazil - Doctorate (Direct)
• Start date: January 01, 2017
• End date: November 30, 2020
• Field of knowledge: Biological Sciences - Physiology - Physiology of Organs and Systems
• Principal Investigator: William Tadeu Lara Festuccia
• Grantee: Érique de Castro
• 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

The identification of good amounts of brown adipose tissue in humans along with beige adipocytes with the ability to express UCP-1 under demand, renewed the interest of studying nonshivering thermogenesis as a strategy to increase energy expenditure and counteract obesity. For this, it is important to develop strategies to recruit brown and beige adipocytes (increase cell number and thermogenic capacity), as well as, switch on and off thermogenesis under desired conditions. Therefore in the current proposal we will test the hypotheses that mTORC 1 and 2 and PPARgamma are important regulators of the leukocyte infiltration, metabolic changes, mitochondrial biogenesis in brown and white adipose tissue induced by cold exposure. For this, mice with gain and loss of function of mTORC1 and 2 and PPARgamma will be evaluated for leukocyte profile, recruitment (hyperplasia and hypertrophy, UCP-1 and mitochondrial content), thermogenic activity (heat production and oxygen consumption) and metabolism (glucose, fatty acids and amino acids) in brown and beige adipocytes after different periods of cold exposure. The involvement of specific leukocytes in the recruitment and activation of brown and beige adipocytes will be also investigated. (AU)

Scientific publications

(8)

(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)

CASTRO, ERIQUE; SILVA, TIAGO E. OLIVEIRA; FESTUCCIA, WILLIAM T.. Critical review of beige adipocyte thermogenic activation and contribution to whole-body energy expenditure. HORMONE MOLECULAR BIOLOGY AND CLINICAL INVESTIGATION, v. 31, n. 2, SI, AUG 2017. (16/23169-9, 16/07062-0, 15/19530-5)

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)

CHAVES-FILHO, ADRIANO B.; PEIXOTO, ALBERT S.; CASTRO, ERIQUE; OLIVEIRA, TIAGO E.; PERANDINI, LUIZ A.; MOREIRA, RAFAEL J.; DA SILVA, RAILMARA P.; DA SILVA, BEATRIZ P.; MORETTI, EDUARDO H.; STEINER, ALEXANDRE A.; et al. Futile cycle of beta-oxidation and de novo lipogenesis are associated with essential fatty acids depletion in lipoatrophy. BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR AND CELL BIOLOGY OF LIPIDS, v. 1868, n. 3, p. 14-pg., 2022-12-20. (16/23169-9, 17/23040-9, 20/04159-8, 18/03418-0, 20/09399-7, 20/12969-0, 19/26473-9, 13/07937-8, 15/19530-5, 18/11156-5, 19/17660-0)

CASTRO, ERIQUE; SILVA, TIAGO E. OLIVEIRA; FESTUCCIA, WILLIAM T.. Critical review of beige adipocyte thermogenic activation and contribution to whole-body energy expenditure. HORMONE MOLECULAR BIOLOGY AND CLINICAL INVESTIGATION, v. 31, n. 2, p. 9-pg., 2017-08-01. (15/19530-5, 16/23169-9, 16/07062-0)

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)

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)

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)

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)

Academic Publications

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

CASTRO, Érique de. mTORC2 in adipocytes is essential to increase cold-induced thermogenic capacity and improve insulin sensitivity induced by cold and high-fat diet rich in omega 3 fatty acids.. 2021. Doctoral Thesis - Universidade de São Paulo (USP). Instituto de Ciências Biomédicas (ICB/SDI) São Paulo.