CXC Ligand 5 Is an Adipose-Tissue Derived Factor that Links Obesity to Insulin Resistance
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Author
Chavey, Carine
Lazennec, Gwendal
Lagarrigue, Sylviane
Clapé, Cyrielle
Iankova, Irena
Teyssier, Jacques
Annicotte, Jean-Sébastien
Schmidt, Julien
Mataki, Chikage
Yamamoto, Hiroyasu
Sanches, Rosario
Guma, Anna
Stich, Vladimir
Vitkova, Michaela
Jardin-Watelet, Bénédicte
Renard, Eric
Strieter, Robert
Tuthill, Antoinette
Vidal-Puig, Antonio
Zorzano, Antonio
Langin, Dominique
Fajas, Lluis
Published Version
https://doi.org/10.1016/j.cmet.2009.03.002Metadata
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Chavey, Carine, Gwendal Lazennec, Sylviane Lagarrigue, Cyrielle Clapé, Irena Iankova, Jacques Teyssier, Jean-Sébastien Annicotte, et al. 2009. “CXC Ligand 5 Is an Adipose-Tissue Derived Factor That Links Obesity to Insulin Resistance.” Cell Metabolism 9 (4): 339–49. https://doi.org/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.Terms of Use
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