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  3. CXC ligand 5 is an adipose-tissue derived factor that links obesity to insulin resistance

CXC ligand 5 is an adipose-tissue derived factor that links obesity to insulin resistance

  • Cell Metab. 2009 Apr;9(4):339-49. doi: 10.1016/j.cmet.2009.03.002.
Carine Chavey 1,  Gwendal Lazennec,  Sylviane Lagarrigue,  Cyrielle Clapé,  Irena Iankova,  Jacques Teyssier,  Jean-Sébastien Annicotte,  Julien Schmidt,  Chikage Mataki,  Hiroyasu Yamamoto,  Rosario Sanches,  Anna Guma,  Vladimir Stich,  Michaela Vitkova,  Bénédicte Jardin-Watelet,  Eric Renard,  Robert Strieter,  Antoinette Tuthill,  Gôkhan S Hotamisligil,  Antonio Vidal-Puig,  Antonio Zorzano,  Dominique Langin,  Lluis Fajas
Affiliations

Affiliation

  • 1 INSERM U834, U896, U834, CRLC Val d'Aurelle, Univ Montpellier 1, F-34295, France.
PMID: 19356715 DOI: 10.1016/j.cmet.2009.03.002
Abstract

We show here high levels of expression and secretion of the chemokine CXC ligand 5 (CXCL5) in the macrophage fraction of white adipose tissue (WAT). Moreover, we find that CXCL5 is dramatically increased in serum of human obese compared to lean subjects. Conversely, CXCL5 concentration is decreased in obese subjects after a weight reduction program, or in obese non-insulin-resistant, compared to insulin-resistant, subjects. Most importantly we demonstrate that treatment with recombinant CXCL5 blocks insulin-stimulated glucose uptake in muscle in mice. CXCL5 blocks Insulin signaling by activating the JAK2/STAT5/SOCS2 pathway. Finally, by treating obese, insulin-resistant mice with either anti-CXCL5 neutralizing Antibodies or antagonists of CXCR2, which is the CXCL5 receptor, we demonstrate that CXCL5 mediates Insulin resistance. Furthermore CXCR2-/- mice are protected against obesity-induced Insulin resistance. Taken together, these results show that secretion of CXCL5 by WAT resident macrophages represents a link between obesity, inflammation, and Insulin resistance.

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