期刊
CELL METABOLISM
卷 9, 期 4, 页码 339-349出版社
CELL PRESS
DOI: 10.1016/j.cmet.2009.03.002
关键词
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资金
- INSERM U858
- INSERM U896
- INSERM, Region Languedoc Roussillon
- Fondation pour la Recherche Medicale (equipe FRM)
- European Commission HEPADIP project [LSHM-CT-2005-018734, ANR (PHYSIO 2006)]
- Agence National pour la Recherche
- National Institutes of Health USA [DK052539]
- Medical Research Council (MRC), UK
- MRC [G0400192, G0600717] Funding Source: UKRI
- Medical Research Council [G0600717, G0400192] Funding Source: researchfish
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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