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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 type:Scholarships in Brazil - Doctorate (Direct)
Effective date (Start): January 01, 2017
Effective date (End): November 30, 2020
Field of knowledge:Biological Sciences - Physiology - Physiology of Organs and Systems
Principal researcher:William Tadeu Lara Festuccia
Grantee:Érique de Castro
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


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)

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Scientific publications (5)
(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, . (15/19530-5, 16/23169-9, 16/07062-0)
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, . (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)
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, . (17/17582-3, 16/23169-9, 15/13508-8, 19/17660-0, 17/17403-1, 13/07937-8, 19/04271-5, 18/11156-5, 15/19530-5, 19/01763-4, 15/22983-1, 17/12260-8, 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, . (16/23169-9, 15/13508-8, 15/19530-5, 16/07062-0, 17/12260-8)
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, . (16/23169-9, 17/17582-3, 15/13508-8, 18/11156-5, 15/19530-5, 15/22983-1, 16/07062-0, 17/12260-8, 17/23040-9)

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