| Literature DB >> 19356715 |
Carine Chavey1, 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.
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.Entities:
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Year: 2009 PMID： 19356715 PMCID： PMC2804846 DOI： 10.1016/j.cmet.2009.03.002
Source DB: PubMed Journal: Cell Metab ISSN： 1550-4131 Impact factor: 27.287