Background: Upon excessive expansion, adipose tissue is infiltrated by macrophages and shows increased production of inflammatory cytokines. This chronic low grade inflammation of adipose tissue is involved in the pathogenesis of insulin resistance. A supplementation with resveratrol can reverse the metabolic disturbances of human obesity, in part by mimicking the effects of caloric restriction.
Objective and Hypotheses: We hypothesized that the beneficial effects of resveratrol might be mediated by an anti-inflammatory effect on adipose tissue.
Method: To mimic adipose tissue inflammation we incubated SGBS adipocytes with THP-1 macrophage conditioned medium (MacCM). Cultures were treated with 100 μM resveratrol or vehicle (DMSO). Interleukin-6 and 8 (IL6, IL8) and monocyte chemo-atractant protein 1 (MCP1) production was studied by qPCR and ELISA.
Results: Treatment of adipocytes with 10% MacCM resulted in upregulation of IL6 mRNA by ~50-fold, IL8 by ~500-fold and MCP-1 by ~25-fold after 48 h. Co-treatment with resveratrol completely abolished this effect of MaCM. Comparable results were found on the protein level. To elicudate the molecular pathway involved, we took advantage of small molecule inhibitors. Inhibition of NFkB with SC-514 (100 μM) prevented the MacCM-induced upregulation of IL6, IL8 and MCP1 production. Interestingly, inhibition of PI3K with Ly294002 (20 μM) did not interfere with IL6 and IL8, but downregulated mRNA expression of MCP1. However, we detected significantly lower amounts of IL6, IL8 and MCP1 secreted to the media supernatants upon inhibition of PI3K.
Conclusion: We show that resveratrol inhibits the inflammation-induced cytokine production in human adipocytes, mediating its anti-inflammatory effect by inhibting NFkB activity and the PI3K/Akt pathway. Taken together, our results demonstrate that resveratrol has health beneficial effects on human adipocytes. Preventing proinflammatory conditions in adipose tissue might be a useful strategy to prevent the development of insulin resistance in the obese state.
20 - 22 Sep 2014
European Society for Paediatric Endocrinology