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 Opportunities: Scholarships in Brazil - Doctorate
• Start date: December 01, 2017
• End date: April 30, 2021
• Field of knowledge: Biological Sciences - Physiology - Physiology of Organs and Systems
• Principal Investigator: Licio Augusto Velloso
• Grantee: Alexandre Moura Assis
• Host 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)

Scientific publications

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

MOURA-ASSIS, ALEXANDRE; JUNIOR, JOSE; GASPAR, JOANA M.; VELLOSO, LICIO; NOGUEIRA, PEDRO AUGUSTO S.. The Knockdown of TRIL in POMC-Expressing Neurons Reduces Body Adiposity and Ameliorates Leptin Responsiveness. Diabetes, v. 69, p. 2-pg., 2020-06-01. (16/01245-5)

MOURA-ASSIS, A.; DE LIMA JUNIOR, J.; GASPAR, J.; GASPAR, R.; ROPELLE, E. R.; VELLOSO, L. A.. The role of TLR4 interactor with leucine-rich repeats (TRIL) in hypothalamic inflammation. Diabetologia, v. 61, p. 2-pg., 2018-10-01. (16/01245-5)

Academic Publications

(References retrieved automatically from State of São Paulo Research Institutions)

ASSIS, Alexandre Moura. Mechanisms of POMC-expressing neurons dysfunction in the hypothalamus of obese mice. 2021. Doctoral Thesis - Universidade Estadual de Campinas (UNICAMP). Faculdade de Ciências Médicas Campinas, SP.