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Study of the impact of Concurrent Exercise training over the acquired lipodystrophy syndrome in mice and humans

Grant number: 17/09917-5
Support type:Scholarships in Brazil - Post-Doctorate
Effective date (Start): November 01, 2017
Effective date (End): March 31, 2018
Field of knowledge:Biological Sciences - Physiology - Physiology of Organs and Systems
Principal Investigator:Marcelo Alves da Silva Mori
Grantee:Rafael Evangelista Pedro
Home Institution: Instituto de Biologia (IB). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil

Abstract

The use of antiretroviral therapy (ART) reduces mortality due to aids-related diseases; however, it is associated with early development of cardiometabolic disorders not related to the infection in people living with HIV/aids (PLWHA). The metabolic and morphological changes in adipose tissue due to ART [i.e. HIV-associated lipodystrophy syndrome (HALS)] play a pivotal role in the etiology of these complications. We have shown that Dicer deletion in adipocytes generates mice with morphological and metabolic characteristics (e.g. decrease in subcutaneous adipose tissue mass, whitening of brown adipose tissue, inflammation, insulin resistance, dyslipidemia, etc) which are similar to HALS. In addition, we showed that PLWHA have decreased expression of Dicer in adipose tissue. This reduction is associated with a reduction in many microRNAs (miRNAs), both in the adipose tissue and in the circulation, which may be the trigger for at least some of the clinical manifestations of PLWHA. On the other hand, physical training has been used as a safe and effective strategy to mitigate the deleterious effects of ART, although its effects on adipose tissue have not been investigated yet. We found that physical training leads to an increase in Dicer and miRNA expression in adipose tissue of mice. Therefore, our aims are: a) to determine the role of ART in adipose tissue Dicer and miRNA expression and their relationship with changes in the inflammatory and metabolic profile of the organism; b) to verify if these changes are associated with brown and beige adipose tissue development, and c) to verify if physical training is able to increase Dicer and miRNA expression in adipose tissue, consequently improving the metabolic status of lipodystrophic mice and PLWHA.