(-)-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

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 ca)-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 cc (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. These findings could be of relevance in the dietary management of obesity and metabolic syndrome.c)) 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. These findings could be of relevance in the dietary management of obesity and metabolic syndrome.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. These findings could be of relevance in the dietary management of obesity and metabolic syndrome.a-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. These findings could be of relevance in the dietary management of obesity and metabolic syndrome.a-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. These findings could be of relevance in the dietary management of obesity and metabolic syndrome.a-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. These findings could be of relevance in the dietary management of obesity and metabolic syndrome.a-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. These findings could be of relevance in the dietary management of obesity and metabolic syndrome.a-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. These findings could be of relevance in the dietary management of obesity and metabolic syndrome.a, 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. These findings could be of relevance in the dietary management of obesity and metabolic syndrome.a-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.