mTOR complex 1 attenuates the proinflammatory macrophage response, and adipose tissue inflammation associated with obesity.

Author(s)

Vivian Almeida Paschoal

• Document type: Doctoral Thesis
• Press: São Paulo.
• Institution: Universidade de São Paulo (USP). Instituto de Ciências Biomédicas (ICB/SDI)
• Defense date: 2015-11-04

Examining board members

William Tadeu Lara Festuccia; Ronaldo de Carvalho Araújo; Niels Olsen Saraiva Câmara; Ana Campa; José Cesar Rosa Neto

• Advisor: William Tadeu Lara Festuccia

Abstract

Pharmacological mTOR inhibition with rapamycin exacerbates the glucose intolerance associated with obesity, such an effect that may be associated to the development of inflammatory process in adipose tissue. Rapamycin treatment exacerbates the glucose intolerance and adipose tissue inflammation induced by high fat diet feeding. In vitro, inhibition of mTOR complexes 1 and 2 with rapamycin and torin induced spontaneous macrophage polarization into a pro-inflammatory M1 phenotype and increased M0 macrophage phagocytosis. Mice with constitutive activation of mTOR complex 1 in myeloid cells were protected from body weight gain, fat accretion, glucose and insulin tolerance induced by the intake of high fat diet and displayed a significant increase in macrophage polarization to a M2 phenotype. Altogether, our findings indicate that the activity of mTOR complex 1 attenuates the development of adipose tissue inflammation induced by high fat feeding, through a mechanism that involves a higher polarization of macrophages to anti-inflammatory M2 phenotype. (AU)

• FAPESP's process: 11/10783-7 - mTOR complex 1 involvement in the control of macrophage function in the chronic inflammatory response associated with obesity and insulin resistance
• Grantee: Vivian Almeida Paschoal
• Support Opportunities: Scholarships in Brazil - Doctorate