Quercetin is equally or more effective than resveratrol in attenuating tumor necrosis factor-[alpha]--mediated inflammation and insulin resistance in primary human adipocytes

Background: Quercetin and trans-resveratrol (trans-RSV) are plant polyphenols reported to reduce inflammation or insulin resistance associated with obesity. Recently, we showed that grape powder extract, which contains quercetin and trans-RSV, attenuates markers of inflammation in human adipocytes and macrophages and insulin resistance in human adipocytes. However, we do not know how quercetin and trans-RSV individually affected these outcomes. Objective: The aim of this study was to examine the extent to which quercetin and trans-RSV prevented inflammation or insulin resistance in primary cultures of human adipocytes treated with tumor necrosis factor-[alpha] (TNF-[alpha]--an inflammatory cytokine elevated in the plasma and adipose tissue of obese, diabetic individuals. Design: Cultures of human adipocytes were pretreated with quercetin and trans-RSV followed by treatment with TNF-[alpha]. Subsequently, gene and protein markers of inflammation and insulin resistance were measured. Results: Quercetin, and to a lesser extent trans-RSV, attenuated the TNF-[alpha]--induced expression of inflammatory genes such as interleukin (IL)-6, IL-1[beta], IL-8, and monocyte chemoattractant protein-1 (MCP-1) and the secretion of IL-6, IL-8, and MCP-1. Quercetin attenuated TNF-[alpha]--mediated phosphorylation of extracellular signal--related kinase and c-Jun-N[H.sub.2] terminal kinase, whereas trans-RSV attenuated only c-Jun-N[H.sub.2] terminal kinase phosphorylation. Quercetin and trans-RSV attenuated TNF-[alpha]--mediated phosphorylation of c-Jun and degradation of inhibitory [kappa]B protein. Quercetin, but not trans-RSV, decreased TNF-[alpha]--induced nuclear factor-[kappa]B transcriptional activity. Quercetin and trans-RSV attenuated the TNF-[alpha]--mediated suppression of peroxisome proliferator--activated receptor [gamma] (PPART) and PPAR[gamma] target genes and of PPAR[gamma] protein concentrations and transcriptional activity. Quercetin prevented the TNF-[alpha]--mediated serine phosphorylation of insulin receptor substrate-1 and protein tyrosine phosphatase-lB gene expression and the suppression of insulin-stimulated glucose uptake, whereas trans-RSV prevented only the TNF-[alpha]--mediated serine phosphorylation of insulin receptor substrate-1. Conclusion: These data suggest that quercetin is equally or more effective than trans-RSV in attenuating TNF-[alpha]--mediated inflammation and insulin resistance in primary human adipocytes. Am J Clin Nutr 2010;92:1511-21. doi: 10.3945/ajcn.2010.29807.