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Effect of anti-inflammatory cholinergic pathway in the metabolic changes following high fat diets

Grant number: 18/15981-0
Support type:Scholarships in Brazil - Master
Effective date (Start): September 01, 2018
Effective date (End): September 30, 2020
Field of knowledge:Biological Sciences - Immunology - Cellular Immunology
Principal Investigator:Denise Morais da Fonseca
Grantee:Luísa Menezes Silva
Home 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, the world has experienced an epidemic of metabolic diseases affecting people at different ages in distinct areas of the globe. Obesity, diabetes, cardiovascular and metabolic disorders are in general characterized as complex diseases because they have multifactorial etiologies that includes a combination of genetic and environmental factors. The immune system actively participates in the pathogenesis of such diseases. In particular, the mucosal-associated immune communicates and controls homeostasis in the different compartments of adipose tissue (Koren, Spor et al., 2011, Tremaroli and Backhed 2012). In this context, an intestinal microbiota plays an active role both in digestion and in the absorption of nutrients, as well as in the local and systemic regulation of the immune system. It has been described that the breakdown of the balance microbiota-diet-host can trigger the development of chronic inflammatory and metabolic diseases (Turnbaugh and Gordon 2009, Turnbaugh, Hamady et al., 2009). At barrier tissues, sites of constant microbial exposure, tissue-specific immunity requires defined structural components that have immunologic and neuroendocrine detectors providing signal for the spatial segregation from the microbiota and infectious agents. This process ensures the maintenance of organ function and enables the balance between tolerance to environmental antigens and regulated protective immunity. Among the different mechanisms studied, emphasis was placed on the neuroimmunological pathways in the maintenance of the immunological and tissue homeostasis. The control of inflammation through the cholinergic anti-inflammatory arc-reflex of the nervous system is one of the neuroimmune mechanisms more studied at the control of immune responses. The cholinergic anti-inflammatory pathway is a physiological mechanism mediated by the vagus nerve by which the central nervous system controls the immune system and may still be a possible strategy for the treatment of inflammatory and infectious diseases (Tracey 2002, Andersson and Tracey 2012). Several studies have reported the existence of an interaction effect between microbiota-immune and nervous system on the susceptibility of a metabolic disease, the so-called brain-gut axis (Schele, Grahnemo et al., 2013, De Vadder, Kovatcheva-Datchary et al., 2014). However, little is known about the influence of the different types of sympathetic and parasympathetic innervation on the immunological and metabolic homeostasis of the visceral adipose tissue. Our preliminary results point out for increased weight gain in mice that were vagotomized and fed with high fat and ketogenic diets when compared to control groups. Therefore, in this project we will study the parasympathetic control of inflammation in adipose tissue in the context of development of metabolic diseases.