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Evaluation of the involvement of TRIL in inflammation and apoptosis of POMC neurons in the hypothalamus of obese mice

Grant number: 16/01245-5
Support type:Scholarships in Brazil - Doctorate
Effective date (Start): December 01, 2017
Status:Discontinued
Field of knowledge:Biological Sciences - Physiology
Principal Investigator:Licio Augusto Velloso
Grantee:Alexandre Moura Assis
Home Institution: Faculdade de Ciências Médicas (FCM). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil
Associated research grant:13/07607-8 - OCRC - Obesity and Comorbidities Research Center, AP.CEPID
Associated scholarship(s):19/12969-2 - Interactions of leptin and PPAR delta in the control of POMC-expressing neurons, BE.EP.DR

Abstract

Obesity represents an important health issue in the world and studies have identified defects in the hypothalamic control of food intake as an important component of the pathogenesis of this disease. The hypothalamus is capable of integrating peripheral and central signals that control caloric intake and energy expenditure. An important part of this control is exerted by a network of neurons controlled primarily by first order neurons of the arcuate nucleus that provide orexigenic (AgRP/NPY) and anorexigenc (POMC/CART) signals. The chronic consumption of dietary fats can trigger an inflammatory response in hypothalamus eventually resulting in the apoptosis of POMC neurons. Toll-Like Receptor 4 (TLR4) has emerged as an important component of this inflammatory process as it responds to saturated fatty acids present in the circulation. Studies have shown that TLR4 signal transduction in Central Nervous System (CNS) requires an accessory protein named TLR4-interactor with Leucine-rich repeats (TRIL). Recently, TRIL was appointed as a novel component of the TLR4 complex and it's ablation in CNS abolishes the immune response in this tissue. Interestingly, different subpopulations of hypothalamic neurons express different levels of TRIL; thus, POMC neurons express high levels, whereas AgRP neurons express low levels of this protein. Here, we hypothesized that TRIL could be responsible for the high predisposition of POMC neurons to diet-induced apoptosis. The objective of the present study is to evaluate the involvement of TRIL in fatty acid-induced POMC apoptosis. We believe the results of this study may contribute for the advance in the understanding of the pathophysiology of obesity and may identify a new potential target for the treatment of this disease. (AU)

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