TY - JOUR
T1 - Macrophage-derived human resistin exacerbates adipose tissue inflammation and insulin resistance in mice
AU - Qatanani, Mohammed
AU - Szwergold, Nava R.
AU - Greaves, David R.
AU - Ahima, Rexford S.
AU - Lazar, Mitchell A.
PY - 2009/3/2
Y1 - 2009/3/2
N2 - 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.
AB - 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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U2 - 10.1172/JCI37273
DO - 10.1172/JCI37273
M3 - Article
C2 - 19188682
AN - SCOPUS:67649869416
SN - 0021-9738
VL - 119
SP - 531
EP - 539
JO - Journal of Clinical Investigation
JF - Journal of Clinical Investigation
IS - 3
ER -