Curcumin and resveratrol inhibit Nuclear Factor-kappaB-mediated cytokine expression in adipocytes
Adipocytes express inflammatory mediators that contribute to the low-level, chronic inflammation found in obese subjects and have been linked to the onset of cardiovascular disorders and insulin resistance associated with type 2 diabetes mellitus. A reduction in inflammatory gene expression in adipocytes would be expected to reverse this low-level, inflammatory state and improve cardiovascular function and insulin sensitivity.
The natural products, curcumin and resveratrol, are established anti-inflammatory compounds that mediate their effects by inhibiting activation of NF-kappaB signaling. In the present study, we examined if these natural products can inhibit NF-kappaB activation in adipocytes and in doing so reduce cytokine expression.
Methods: Cytokine (TNF-alpha, IL-1beta, IL-6) and COX-2 gene expression in 3T3-L1-derived adipocytes was measured by quantitative real-time PCR (qRT-PCR) with or without TNFalpha-stimulation.
Cytokine protein and prostaglandin E2 (PGE2) expression were measured by ELISA. Effects of curcumin and resveratrol were evaluated by treating TNFalpha-stimulated adipocytes with each compound and 1) assessing the activation state of the NF-kappaB signaling pathway and 2) measuring inflammatory gene expression by qRT-PCR and ELISA.
Results: Both preadipocytes and differentiated adipocytes express the genes for TNF-alpha, IL-6, and COX-2, key mediators of the inflammatory response.
Preadipocytes were also found to express IL-1beta; however, IL-1beta expression was absent in differentiated adipocytes. TNF-alpha treatment activated NF-kappaB signaling in differentiated adipocytes by inducing IkappaB degradation and NF-kappaB translocation to the nucleus, and as a result increased IL-6 (6-fold) and COX-2 (2.5-fold) mRNA levels.
TNF-alpha also activated IL-1beta gene expression in differentiated adipocytes, but had no effect on endogenous TNF-alpha mRNA levels. No detectable TNF-alpha or IL-1beta was secreted by adipocytes.
Curcumin and resveratrol treatment inhibited NF-kappaB activation and resulted in a reduction of TNF-alpha, IL-1beta, IL-6, and COX-2 gene expression (IC50 ~2uM) and a reduction of secreted IL-6 and PGE2 (IC50 ~20uM).
Conclusions: Curcumin and resveratrol are able to inhibit TNFalpha-activated NF-kappaB signaling in adipocytes and as a result significantly reduce cytokine expression. These data suggest that curcumin and resveratrol may provide a novel and safe approach to reduce or inhibit the chronic inflammatory properties of adipose tissue.
Author: Amanda M Gonzales and Robert A Orlando
Credits/Source: Nutrition &Metabolism 2008, 5:17
Published on: 2008-06-13
Copyright by the authors listed above - made available via BioMedCentral (Open Access). Please
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