Please use this identifier to cite or link to this item: http://repositorio.ufla.br/jspui/handle/1/45959
Title: Fractalkine (CX3CL1) Is Involved in the Early Activation of Hypothalamic Inflammation in Experimental Obesity
Keywords: Obesity
Hypothalamic inflammation
Glucose intolerance
Obesidade
Inflamação hipotalâmica
Intolerância à glicose
Issue Date: Nov-2014
Publisher: American Diabetes Association
Citation: MORARI, J. et al. Fractalkine (CX3CL1) Is Involved in the Early Activation of Hypothalamic Inflammation in Experimental Obesity. Diabetes, [S. l.], v. 63, p. 3770-3784, Nov. 2014.
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.
URI: https://diabetes.diabetesjournals.org/content/63/11/3770
http://repositorio.ufla.br/jspui/handle/1/45959
Appears in Collections:DME - Artigos publicados em periódicos

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