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Type: Artigo de periódico
Title: Fractalkine (cx3cl1) Is Involved In The Early Activation Of Hypothalamic Inflammation In Experimental Obesity.
Author: Morari, Joseane
Anhe, Gabriel F
Nascimento, Lucas F
de Moura, Rodrigo F
Razolli, Daniela
Solon, Carina
Guadagnini, Dioze
Souza, Gabriela
Mattos, Alexandre H
Tobar, Natalia
Ramos, Celso D
Pascoal, Vinicius D
Saad, Mario J
Lopes-Cendes, Iscia
Moraes, Juliana C
Velloso, Licio A
Abstract: Hypothalamic inflammation is a common feature of experimental obesity. Dietary fats are important triggers of this process, inducing the activation of toll-like receptor-4 (TLR4) signaling and endoplasmic reticulum stress. Microglia cells, which are the cellular components of the innate immune system in the brain, are expected to play a role in the early activation of diet-induced hypothalamic inflammation. Here, we use bone marrow transplants to generate mice chimeras that express a functional TLR4 in the entire body except in bone marrow-derived cells or only in bone marrow-derived cells. We show that a functional TLR4 in bone marrow-derived cells is required for the complete expression of the diet-induced obese phenotype and for the perpetuation of inflammation in the hypothalamus. In an obesity-prone mouse strain, the chemokine CX3CL1 (fractalkine) is rapidly induced in the neurons of the hypothalamus after the introduction of a high-fat diet. The inhibition of hypothalamic fractalkine reduces diet-induced hypothalamic inflammation and the recruitment of bone marrow-derived monocytic cells to the hypothalamus; in addition, this inhibition reduces obesity and protects against diet-induced glucose intolerance. Thus, fractalkine is an important player in the early induction of diet-induced hypothalamic inflammation, and its inhibition impairs the induction of the obese and glucose intolerance phenotypes.
Subject: Animals
Chemokine Cx3cl1
Diet, High-fat
Flow Cytometry
Real-time Polymerase Chain Reaction
Signal Transduction
Toll-like Receptor 4
Citation: Diabetes. v. 63, n. 11, p. 3770-84, 2014-Nov.
Rights: fechado
Identifier DOI: 10.2337/db13-1495
Date Issue: 2014
Appears in Collections:Unicamp - Artigos e Outros Documentos

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