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

VAZQUEZ-PRIETO, MARCELA; BETTAIEB, AHMED; HAJ, FAWAZ; C. G. FRAGA; P. I. OTEIZA

ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS

ELSEVIER SCIENCE INC

Lugar: Amsterdam; Año: 2012 vol. 527 p. 113 - 118

0003-9861

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 (TNFa)-induced activation of cell signals involved in inflammation and insulin resistance (NF-jB, mitogen-activated protein kinases (MAPKs), AP-1, and peroxisome proliferator activated receptor c (PPARc)) in differentiated white adipocytes (3T3-L1). TNFa triggered the activation of transcription factors NF-jB and AP-1, and MAPKs ERK1/2, JNK, and p38. (_)-Epicatechin caused a dose (0.5–10 lM)- dependent decrease in TNFa-mediated JNK, ERK1/2, and p-38 phosphorylation, and nuclear AP-1-DNA binding. (_)-Epicatechin also inhibited TNFa-triggered activation of the NF-jB signaling cascade, preventing TNFa-mediated p65 nuclear transport and nuclear NF-jB-DNA binding. (_)-Epicatechin also attenuated the TNFa-mediated downregulation of PPARc expression and decreased nuclear DNA binding. Accordingly, (_)-epicatechin inhibited TNFa-mediated altered transcription of genes (MCP-1, interleukin-6, TNFa, resistin, and protein-tyrosine phosphatase 1B) involved in inflammation and insulin signaling. In conclusion, (_)-epicatechin can attenuate TNFa-mediated triggering of signaling cascades involved in inflammation and insulin resistance.