title: Fractalkine (CX3CL1) is involved in the early activation of hypothalamic inflammation in experimental obesity.
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.
authors.affiliation: Laboratory of Cell Signaling, University of Campinas, Campinas, Brazil.
authors.forename: Joseane
authors.initials: J
authors.lastname: Morari
authors.affiliation: Department of Pharmacology, University of Campinas, Campinas, Brazil.
authors.forename: Gabriel F
authors.initials: GF
authors.lastname: Anhe
authors.affiliation: Laboratory of Cell Signaling, University of Campinas, Campinas, Brazil.
authors.forename: Lucas F
authors.initials: LF
authors.lastname: Nascimento
authors.affiliation: Laboratory of Cell Signaling, University of Campinas, Campinas, Brazil.
authors.forename: Rodrigo F
authors.initials: RF
authors.lastname: de Moura
authors.affiliation: Laboratory of Cell Signaling, University of Campinas, Campinas, Brazil.
authors.forename: Daniela
authors.initials: D
authors.lastname: Razolli
authors.affiliation: Laboratory of Cell Signaling, University of Campinas, Campinas, Brazil.
authors.forename: Carina
authors.initials: C
authors.lastname: Solon
authors.affiliation: Laboratory of Experimental Endocrinology, University of Campinas, Campinas, Brazil.
authors.forename: Dioze
authors.initials: D
authors.lastname: Guadagnini
authors.affiliation: Laboratory of Cell Signaling, University of Campinas, Campinas, Brazil.
authors.forename: Gabriela
authors.initials: G
authors.lastname: Souza
authors.affiliation: Department of Medical Genetics, University of Campinas, Campinas, Brazil.
authors.forename: Alexandre H
authors.initials: AH
authors.lastname: Mattos
authors.affiliation: Department of Radiology, University of Campinas, Campinas, Brazil.
authors.forename: Natalia
authors.initials: N
authors.lastname: Tobar
authors.affiliation: Department of Radiology, University of Campinas, Campinas, Brazil.
authors.forename: Celso D
authors.initials: CD
authors.lastname: Ramos
authors.affiliation: Department of Medical Genetics, University of Campinas, Campinas, Brazil.
authors.forename: Vinicius D
authors.initials: VD
authors.lastname: Pascoal
authors.affiliation: Laboratory of Experimental Endocrinology, University of Campinas, Campinas, Brazil.
authors.forename: Mario J
authors.initials: MJ
authors.lastname: Saad
authors.affiliation: Department of Medical Genetics, University of Campinas, Campinas, Brazil.
authors.forename: Iscia
authors.initials: I
authors.lastname: Lopes-Cendes
authors.affiliation: Laboratory of Cell Signaling, University of Campinas, Campinas, Brazil.
authors.forename: Juliana C
authors.initials: JC
authors.lastname: Moraes
authors.affiliation: Laboratory of Cell Signaling, University of Campinas, Campinas, Brazil lavelloso.unicamp@gmail.com.
authors.forename: Licio A
authors.initials: LA
authors.lastname: Velloso
mesh_terms: D000818:Animals; D054428:Chemokine CX3CL1 / Q000235:genetics / Q000378:metabolism*; D059305:Diet, High-Fat / Q000009:adverse effects; D005434:Flow Cytometry; D007031:Hypothalamus / Q000276:immunology / Q000378:metabolism*; D015151:Immunoblotting; D007249:Inflammation / Q000209:etiology / Q000276:immunology / Q000378:metabolism*; D008297:Male; D051379:Mice; D009765:Obesity / Q000209:etiology / Q000276:immunology / Q000378:metabolism*; D060888:Real-Time Polymerase Chain Reaction; D015398:Signal Transduction; D051197:Toll-Like Receptor 4 / Q000378:metabolism
chemical_list: D054428:Chemokine CX3CL1; D051197:Toll-Like Receptor 4