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

Mohammed Qatanani, Nava R. Szwergold, David R. Greaves, Rexford S. Ahima, Mitchell A. Lazar

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish (US)
Pages (from-to)531-539
Number of pages9
JournalJournal of Clinical Investigation
Volume119
Issue number3
DOIs
StatePublished - Mar 2 2009

ASJC Scopus subject areas

  • Medicine(all)

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