Fractalkine (CX3CL1) is involved in the early activation of hypothalamic inflammation in experimental obesity

  1. Licio A. Velloso1
  1. 1Laboratory of Cell Signaling,
  2. 2Department of Pharmacology,
  3. 3Laboratory of Experimental Endocrinology,
  4. 4Department of Medical Genetics,
  5. 5Department of Radiology, University of Campinas, Brazil
  1. Corresponding Author: Licio A. Velloso, E-mail: lavelloso.unicamp{at}


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 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 following 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.

  • Received September 29, 2013.
  • Accepted May 28, 2014.

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