(-)-Epicatechin prevents TNFα-induced activation of signaling cascades involved in inflammation and insulin sensitivity in 3T3-L1 adipocytes

Obesity is major public health concern worldwide and obese individuals exhibit a higher risk of chronic diseases such as type 2 diabetes. Inflammation plays a significant role in metabolic regulation and mounting evidence highlight the contribution of adipose tissue to systemic inflammatory state. Food extracts with a high content of (-)-epicatechin have been found to exert systemic anti-inflammatory actions, however the anti-inflammatory actions of (-)-epicatechin on adipose tissue remain to be determined. The aim of this study was to investigate the capacity of (-)-epicatechin to prevent tumor necrosis alpha (TNF alpha)-induced activation of cell signals involved in inflammation and insulin resistance (NF-kappa B, mitogen-activated protein kinases (MAPKs), AP-1, and peroxisome proliferator activated receptor gamma (PPAR gamma)) in differentiated white adipocytes (3T3-L1). TNF alpha triggered the activation of transcription factors NF-kappa B and AP-1, and MAPKs ERK1/2, JNK, and p38. (-)-Epicatechin caused a dose (0.5-10 mu M)-dependent decrease in TNF alpha-mediated JNK, ERK1/2, and p-38 phosphorylation, and nuclear AP-1-DNA binding. (-)-Epicatechin also inhibited TNF alpha-triggered activation of the NF-kappa B signaling cascade, preventing TNF alpha-mediated p65 nuclear transport and nuclear NF-kappa B-DNA binding. (-)-Epicatechin also attenuated the TNF alpha-mediated downregulation of PPAR gamma expression and decreased nuclear DNA binding. Accordingly, (-)-epicatechin inhibited TNF alpha-mediated altered transcription of genes (MCP-1, interleukin-6, TNF alpha, resistin, and protein-tyrosine phosphatase 1B) involved in inflammation and insulin signaling. In conclusion, (-)-epicatechin can attenuate TNF alpha-mediated triggering of signaling cascades involved in inflammation and insulin resistance. These findings could be of relevance in the dietary management of obesity and metabolic syndrome. (C) 2012 Elsevier Inc. All rights reserved.