Quercetin attenuates inflammation in human macrophages and adipocytes exposed to macrophage-conditioned media

Background: Obesity is linked to chronic inflammation in white adipose tissue, which is exacerbated by infiltrating macrophages (MFs). We recently demonstrated that an extract from grape powder (GPE), which is abundant in quercetin (QUE), reduced inflammation in human MFs and prevented MF-mediated inflammation and insulin resistance in human adipocytes. However, we did not know how QUE individually affected these outcomes. Objective and design: We examined the extent to which QUE prevents inflammation in human MFs (that is, differentiated U937 cell line) and cross-talk with human adipocytes (that is, primary cultures of newly differentiated human adipocytes). Methods and results: Treatment of MFs with QUE attenuated the basal expression of inflammatory genes, such as tumor necrosis factor-a, interleukin (IL)-6, IL-8, IL-1 beta and interferon-g inducible protein-10, and cyclooxygenase-2, a marker of prostaglandin production. QUE also attenuated the abundance of phosphorylated c-Jun N-terminal kinase (JNK) and c-Jun, and I kappa B alpha degradation in MFs. Furthermore, conditioned media (CM) obtained from MFs treated with QUE decreased the capacity of this CM to inflame adipocytes and cause insulin resistance as evidenced by decreased: (1) inflammatory gene expression, (2) phosphorylation of JNK and c-Jun, (3) serine residue 307 phosphorylation of insulin receptor substrate (IRS)-1, 4) protein tyrosine phosphatase-1B gene expression and 5) suppression of insulin-stimulated glucose uptake. Conclusion: Taken together, these data suggest that QUE is one of the bioactive components of GPE that prevents inflammation in MFs and MF-mediated insulin resistance in adipocytes. International Journal of Obesity (2011) 35, 1165-1172; doi:10.1038/ijo.2010.272; published online 11 January 2011