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Publication : Macrophage-derived human resistin exacerbates adipose tissue inflammation and insulin resistance in mice.

First Author  Qatanani M Year  2009
Journal  J Clin Invest Volume  119
Issue  3 Pages  531-9
PubMed ID  19188682 Mgi Jnum  J:171262
Mgi Id  MGI:4949119 Doi  10.1172/JCI37273
Citation  Qatanani M, et al. (2009) Macrophage-derived human resistin exacerbates adipose tissue inflammation and insulin resistance in mice. J Clin Invest 119(3):531-9
abstractText  Resistin is an adipokine that contributes to insulin resistance in mice. In humans, however, studies investigating the link between resistin and metabolic disease are conflicting. Further complicating the matter, human resistin is produced mainly by macrophages rather than adipocytes. To address this important issue, we generated mice that lack adipocyte-derived mouse resistin but produce human resistin in a pattern similar to that found in humans, i.e., in macrophages (humanized resistin mice). When placed on a high-fat diet, the humanized resistin mice rapidly developed accelerated white adipose tissue (WAT) inflammation, leading to increased lipolysis and increased serum free fatty acids. Over time, these mice accumulated lipids, including diacylglycerols, in muscle. We found that this resulted in increased Pkcq pathway activity, leading to increased serine phosphorylation of Irs-1 and insulin resistance. Thus, although the site of resistin production differs between species, human resistin exacerbates WAT inflammation and contributes to insulin resistance.
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