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Alterations in adipogenesis and apoptosis in different adipose territories induced by the chronic iatrogenic hypercortisolism

Grant number: 19/19669-4
Support type:Scholarships in Brazil - Post-Doctorate
Effective date (Start): October 01, 2019
Effective date (End): September 30, 2021
Field of knowledge:Biological Sciences - Physiology - Physiology of Organs and Systems
Principal Investigator:Fabio Bessa Lima
Grantee:Rafael Barrera Salgueiro
Home Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil
Associated research grant:16/25129-4 - Iatrogenic Chronic Hypercortisolism and its implications to the adipose tissue plasticity an analysis of the dynamics of adipose tissue distribution in an experimental model of Cushing's Syndrome, AP.TEM

Abstract

Cushing's syndrome is a disease characterized by excessive (endogenous or iatrogenic) exposure to glucocorticoids, resulting in corticotropic axis dysfunction. Within this metabolic syndrome there are classic components: body fat redistribution with increased central adiposity and limb reduction, insulin resistance, dyslipidemia, muscle atrophy, osteopenia, abdominal striae, exacerbated protein catabolism. Recently in our laboratory we were able to reproduce this clinical picture using a prolonged (4 weeks) glucocorticoid infusion model using a minipump in rats. With this study, we intend to evaluate the mechanisms that interfere with the body fat distribution pattern of these animals, in particular, how glucocorticoids modify cell turnover (adipogenesis and apoptosis). The analysis will involve in vivo and in vitro experiments, and molecular studies (protein and gene expression evaluation). We consider that Cushing's iatrogenic induction model is an interesting approach for understanding how changes in the dynamics of adipose tissue plasticity are processed and by which basic mechanisms this regulation occurs. We believe that the knowledge that will emerge from these studies may contribute to the development of therapeutic strategies for the treatment of tissue-impacting diseases such as obesity and lipodystrophies.