Constitutive adipocyte mTORC1 activation enhances mitochondrial activity and reduces visceral adiposity in mice

Juliana Magdalon, Patricia Chimin, Thiago Belchior, Rodrigo X. Neves, Marcel A. Vieira-Lara, Maynara L. Andrade, Talita S. Farias, Andressa Bolsoni-Lopes, Vivian A. Paschoal, Alex S. Yamashita, Alicia J. Kowaltowski, William T. Festuccia

Research output: Contribution to journalArticlepeer-review

Abstract

Mechanistic target of rapamycin complex 1 (mTORC1) loss of function reduces adiposity whereas partial mTORC1 inhibition enhances fat deposition. Herein we evaluated how constitutive mTORC1 activation in adipocytes modulates adiposity in vivo. Mice with constitutive mTORC1 activation in adipocytes induced by tuberous sclerosis complex (Tsc)1 deletion and littermate controls were evaluated for body mass, energy expenditure, glucose and fatty acid metabolism, mitochondrial function, mRNA and protein contents. Adipocyte-specific Tsc1 deletion reduced visceral, but not subcutaneous, fat mass, as well as adipocyte number and diameter, phenotypes that were associated with increased lipolysis, UCP-1 content (browning) and mRNA levels of pro-browning transcriptional factors C/EBPβ and ERRα. Adipocyte Tsc1 deletion enhanced mitochondrial oxidative activity, fatty acid oxidation and the expression of PGC-1α and PPARα in both visceral and subcutaneous fat. In brown adipocytes, however, Tsc1 deletion did not affect UCP-1 content and basal respiration. Adipocyte Tsc1 deletion also reduced visceral adiposity and enhanced glucose tolerance, liver and muscle insulin signaling and adiponectin secretion in mice fed with purified low- or high-fat diet. In conclusion, adipocyte-specific Tsc1 deletion enhances mitochondrial activity, induces browning and reduces visceral adiposity in mice.

Original languageEnglish (US)
Pages (from-to)430-438
Number of pages9
JournalBiochimica et Biophysica Acta - Molecular and Cell Biology of Lipids
Volume1861
Issue number5
DOIs
StatePublished - May 2016
Externally publishedYes

Keywords

  • Adiposity
  • Browning
  • Fatty acid oxidation
  • Mitochondria
  • UCP-1
  • mTOR

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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