Scholarship 19/14026-8 - Tecido adiposo, Microbioma gastrointestinal - BV FAPESP
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Contribution of short chain fatty acids to the development of non-classical metabolic syndrome after acute intestinal infection

Grant number: 19/14026-8
Support Opportunities:Scholarships in Brazil - Master
Start date: August 01, 2019
End date: April 30, 2021
Field of knowledge:Biological Sciences - Immunology - Cellular Immunology
Principal Investigator:Denise Morais da Fonseca
Grantee:Bárbara Cristina Pizzolante
Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil
Associated research grant:15/25364-0 - Impact of infection-induced immunological scarring on the long-term host metabolic homeostasis, AP.JP

Abstract

In the past few years, metabolic disorders, such as obesity, diabetes, cardiovascular diseases and metabolic syndromes, have been included in the categories of complex diseases trigged by several endogenous and exogenous stressors. Indeed, it has been shown that there is an important crosstalk between the immune system and gut microorganisms during the development of obesity and metabolic syndromes. Chronic inflammation in the adipose tissue is a common finding and it had been associated with the pathogenesis of those diseases. However, the role of the microbiota and the functional impact of infections in such diseases are not fully understood. This is largely due to the complexity of the microbiota components and the bidirectional involvement of different host physiological systems in the maintenance of intestinal homeostasis, such as the immune and the neuroendocrine systems. Such a scenario is even more complex in individuals who are constantly exposed to gastrointestinal infections. The microbiota also plays a key role in the production of metabolites that are absorbed by the body, including short chain fatty acids (SCFA). SCFAs directly influence the immune system and may have pro- and anti-inflammatory effects. Recently, we have shown that a single episode of acute gastrointestinal infection with Yersinia pseudotuberculosis can lead to the development of immunological scaring causing irreversible long-term consequences to tissue specific immunity. Notably, this immunological scar is characterized by the disruption of gut-immune system dialog, loss of compartmentalization of the microbiota and remodeling of the mesentery, including adipose tissue and associated lymphoid tissue. In parallel we have shown that previously infected mice develop a non-classical type of metabolic syndrome, characterized by a significant improvement in the carbohydrate metabolism associated with a complete shut down in the capacity of those animals for using lipids as an energy source. Improvement in carbohydrate metabolism is associated with increased expression of UCP1 and beigeing in white adipose tissue, which acquires characteristics of brown adipose tissue. This phenotype can be partially transferred by transplantation of white adipose tissue. The hypothesis of this project is that the chronic inflammation of adipose tissue that develops after infection is associated with the development of this non-classical metabolic syndrome. We still believe that there are mechanisms of direct communication and immunological signaling between the intestine and the different deposits of adipose tissue. To better study the pathogenesis of this metabolic disorder, the main objective of this project is to study the mechanisms involved in the maintenance of chronic inflammation of adipose tissue after acute intestinal infection with emphasis on the production of SCFA by the host, since the intestinal microbiota permanently altered. (AU)

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Academic Publications
(References retrieved automatically from State of São Paulo Research Institutions)
PIZZOLANTE, Bárbara Cristina. Mechanisms involved in chronic inflammation of adipose tissue after acute intestinal infection: contribution of the Th2 response and short-chain fatty acids. 2021. Master's Dissertation - Universidade de São Paulo (USP). Instituto de Ciências Biomédicas (ICB/SDI) São Paulo.