Adipocyte-derived factors potentiate nutrient-induced production of plasminogen activator inhibitor-1 by macrophages

Preeti Kishore, Weijie Li, Julia Tonelli, Do Eun Lee, Sudha Koppaka, Kehao Zhang, Ying Lin, Sylvia Kehlenbrink, Philipp E. Scherer, Meredith Hawkins

Research output: Contribution to journalArticle

42 Scopus citations

Abstract

Macrophages are more abundant in adipose tissue from obese individuals than from those of normal weight and may contribute to the metabolic consequences of obesity by producing various circulating factors. One of these factors is plasminogen activator inhibitor-1 (PAI-1), which contributes to both atherosclerosis and insulin resistance. Because nutritional factors appear to regulate PAI-1 expression, we hypothesized that exposure to fatty acids and adipocyte secretory products could stimulate production of PAI-1 by adipose macrophages. Increased free fatty acid (FFA) concentrations in blood for 5 hours in nondiabetic, overweight subjects markedly suppressed insulin-stimulated glucose uptake and raised circulating PAI-1 concentrations, with a concomitant increase in the expression of the PAI-1 gene in adipose tissue. FFAs also rapidly increased PAI-1 gene expression in adipose macrophages and PAI-1 protein immunofluorescence surrounding these cells. By contrast, PAI-1 expression in circulating monocytes was very low and was not affected by raising the concentration of FFAs. Medium from cultured adipocytes stimulated PAI-1 expression in cultured macrophages and potentiated the increase in PAI-1 messenger RNA expression in response to FFAs. Together, our data suggest that adipocyte-derived factors prime adipose macrophages so that they respond to nutritional signals (FFAs) by releasing a key inflammatory adipokine, PAI-1.

Original languageEnglish (US)
Pages (from-to)20ra15
JournalScience Translational Medicine
Volume2
Issue number20
DOIs
StatePublished - Jun 7 2010

ASJC Scopus subject areas

  • Medicine(all)

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