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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

Adipocyte-specific mTORC2 deficiency impairs BAT and iWAT thermogenic capacity without affecting glucose uptake and energy expenditure in cold-acclimated mice

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Castro, Erique [1] ; Vieira, Thayna S. [1] ; Oliveira, Tiago E. [1] ; Ortiz-Silva, Milene [1] ; Andrade, Maynara L. [1] ; Tomazelli, Caroline A. [1] ; Peixoto, Albert S. [1] ; Sobrinho, Cleyton R. [1] ; Moreno, Mayara F. [1] ; Gilio, Gustavo R. [1] ; Moreira, Rafael J. [1] ; Guimaraes, Raphael C. [1] ; Perandini, Luiz A. [1] ; Chimin, Patricia [2] ; Reckziegel, Patricia [3] ; Moretti, Eduardo H. [4] ; Steiner, Alexandre A. [4] ; Laplante, Mathieu [5, 6] ; Festuccia, William T. [1]
Total Authors: 19
Affiliation:
[1] Univ Sao Paulo, Inst Biomed Sci, Dept Physiol & Biophys, Sao Paulo - Brazil
[2] Univ Estadual Londrina, Phys Educ & Sports Ctr, Dept Phys Educ, Londrina, Parana - Brazil
[3] Univ Fed Sao Paulo UNIFESP, Dept Pharmacol, Escola Paulista Med, Sao Paulo - Brazil
[4] Univ Sao Paulo, Inst Biomed Sci, Dept Immunol, Sao Paulo - Brazil
[5] Univ Laval, Inst Univ Cardiol & Pneumol Quebec, Quebec City, PQ - Canada
[6] Univ Laval, Ctr Rech Canc Univ Laval, Quebec City, PQ - Canada
Total Affiliations: 6
Document type: Journal article
Source: AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM; v. 321, n. 5, p. E592-E605, NOV 2021.
Web of Science Citations: 0
Abstract

Deletion of mechanistic target of rapamycin complex 2 (mTORC2) essential component rapamycin insensitive companion of mTOR (Rictor) by a Cre recombinase under control of the broad, nonadipocyte-specific aP2/FABP4 promoter impairs thermoregulation and brown adipose tissue (BAT) glucose uptake on acute cold exposure. We investigated herein whether adipocyte-specific mTORC2 deficiency affects BAT and inguinal white adipose tissue (iWAT) signaling, metabolism, and thermogenesis in cold-acclimated mice. For this, 8-wk-old male mice bearing Rictor deletion and therefore mTORC2 deficiency in adipocytes (adiponectin-Cre) and littermates controls were either kept at thermoneutrality (30 +/- 1 degrees C) or cold-acclimated (10 +/- 1 degrees C) for 14 days and evaluated for BAT and iWAT signaling, metabolism, and thermogenesis. Cold acclimation inhibited mTORC2 in BAT and iWAT, but its residual activity is still required for the cold-induced increases in BAT adipocyte number, total UCP-1 content and mRNA levels of proliferation markers Ki67 and cyclin 1 D, and de novo lipogenesis enzymes ATP-citrate lyase and acetyl-Co A carboxylase. In iWAT, mTORC2 residual activity is partially required for the cold-induced increases in multilocular adipocytes, mitochondrial mass, and uncoupling protein 1 (UCP-1) content. Conversely, BAT mTORC1 activity and BAT and iWAT glucose uptake were upregulated by cold independently of mTORC2. Noteworthy, the impairment in BAT and iWAT total UCP-1 content and thermogenic capacity induced by adipocyte mTORC2 deficiency had no major impact on whole body energy expenditure in cold-acclimated mice due to a compensatory activation of muscle shivering. In conclusion, adipocyte mTORC2 deficiency impairs, through different mechanisms, BAT and iWAT total UCP-1 content and thermogenic capacity in cold-acclimated mice, without affecting glucose uptake and whole body energy expenditure. NEW \& NOTEWORTHY BAT and iWAT mTORC2 is inhibited by cold acclimation, but its residual activity is required for cold induced increases in total UCP-1 content and thermogenic capacity, but not glucose uptake and mTORC1 activity. The impaired BAT and iWAT total UCP-1 content and thermogenic capacity induced by adipocyte mTORC2 deficiency are compensated by activation of muscle shivering in cold-acclimated mice. (AU)

FAPESP's process: 16/23169-9 - 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
Grantee:Érique de Castro
Support type: Scholarships in Brazil - Doctorate (Direct)
FAPESP's process: 19/25943-1 - Intracellular peptides as modulators of thermogenesis-related metabolic pathways
Grantee:Patrícia Reckziegel
Support type: Research Grants - Young Investigators Grants
FAPESP's process: 17/23040-9 - Characterization of mTORC2 role in the hepatic steatosis, steatohepatitis and hepatocellular carcinoma progression induced by PTEN deletion in hepatocytes
Grantee:Álbert Souza Peixoto
Support type: Scholarships in Brazil - Doctorate
FAPESP's process: 15/13508-8 - Involvement of adipocytes mTOR complexes 1 and 2 in the morphological, metabolic and secretory changes induced by pharmacological PPARgamma activation
Grantee:Maynara Lucca Andrade
Support type: Scholarships in Brazil - Doctorate
FAPESP's process: 17/17582-3 - Characterization of the involvement of nutrient sensor mTORC1 in the hepatic steatosis, steatohepatitis, and hepatocarcinoma induced by PTEN deletion into hepatocytes
Grantee:Mayara Franzoi Moreno
Support type: Scholarships in Brazil - Post-Doctorate
FAPESP's process: 18/03418-0 - Hypothermia in Sepsis: causes and consequences
Grantee:Alexandre Alarcon Steiner
Support type: Research Projects - Thematic Grants
FAPESP's process: 17/17403-1 - Characterization of the molecular mechanisms by which TSC1 deletion in adipocytes increases oxidative metabolism and UCP1 content in white adipose tissue
Grantee:Thayna dos Santos Vieira
Support type: Scholarships in Brazil - Scientific Initiation
FAPESP's process: 17/12260-8 - Autophagy involvement in the metabolic and inflammatory alterations in adipose tissue associated with Obesity induced by high fat diet
Grantee:Milene Ortiz Silva
Support type: Scholarships in Brazil - Doctorate (Direct)
FAPESP's process: 19/01763-4 - Characterization of the molecular mechanisms determining the energy balance, glucose homeostasis and hepatomegaly in mice with severe lipodystrophy
Grantee:William Tadeu Lara Festuccia
Support type: Regular Research Grants
FAPESP's process: 19/17660-0 - Discovery of new transcription factors involved in the development of steatosis, steatopatite and hepatocarcinome
Grantee:Luiz Augusto Buoro Perandini
Support type: Scholarships in Brazil - Post-Doctorate
FAPESP's process: 15/19530-5 - Involvement of the nutrient sensor mTOR in the development of obesity associated chronic metabolic diseases
Grantee:William Tadeu Lara Festuccia
Support type: Research Projects - Thematic Grants
FAPESP's process: 20/09399-7 - Development of hypothermia in systemic inflammation: the brain hypoxia hypothesis
Grantee:Eduardo Hermogenes Moretti
Support type: Scholarships in Brazil - Post-Doctorate
FAPESP's process: 19/04271-5 - UCP1-independent mechanisms involved in the increased energy expenditure and protection against Obesity induced by fish oil in mice
Grantee:Tiago Eugênio Oliveira da Silva
Support type: Scholarships in Brazil - Doctorate
FAPESP's process: 12/25317-4 - Involvement of mTOR complex 1 and 2 in secretory control of lipid and protein inflammatory mediators by adipocytes in obesity and insulin resistance conditions.
Grantee:Patricia Chimin
Support type: Scholarships in Brazil - Post-Doctorate