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Constitutive adipocyte mTORC1 activation enhances mitochondrial oxidative capacity and reduces visceral adiposity in mice.

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Juliana Magdalon
Total Authors: 1
Document type: Doctoral Thesis
Press: São Paulo.
Institution: Universidade de São Paulo (USP). Instituto de Ciências Biomédicas (ICB/SDI)
Defense date:
Examining board members:
William Tadeu Lara Festuccia; Marcelo Augusto Christoffolete; Alícia Juliana Kowaltowski; Marcelo Alves da Silva Mori; Lício Augusto Velloso
Advisor: William Tadeu Lara Festuccia

The activity of mechanistic target of rapamycin complex 1 (mTORC1), an important regulator of adiposity and lipid metabolism, is increased in adipose tissue of obese mice. Complete mTORC1 inhibition reduces adiposity, whereas partial mTORC1 inhibition enhances diet-induced obesity. Therefore, we hypothesized that an optimal level of mTORC1 activity is required to increase adiposity, in such a manner that mTORC1 overactivation is as inhibitory to fat deposition as its complete inhibition. To test this hypothesis, we investigated the effects of constitutive mTORC1 activation, induced by Tsc1 deletion, specifically in adipocytes on adiposity in vivo. Tsc1 deletion reduced visceral, but not subcutaneous, fat mass, which was associated with increased lipolysis and browning. Moreover, it enhanced mitochondrial mass and oxidative activity in both visceral and subcutaneous fat. These data support our hypothesis that an optimal level of mTORC1 activation is necessary to increase adiposity. (AU)

FAPESP's process: 11/03972-8 - Modulation of transcriptional activity of nuclear receptors PPAR-gamma, GR and TR-alpha by mTORC1 during and after adipogenesis
Grantee:Juliana Magdalon
Support Opportunities: Scholarships in Brazil - Doctorate