(-)-EPICATECHIN PREVENTS THE ACTIVATION OF PROINFLAMMATORY SIGNALlNG CASCADES IN ADIPOCYTES.

PATRICIA OTEIZA; MARCELA VÁZQUEZ; ROBERTO MIATELLO; CESAR G. FRAGA

Barcelona

Congreso; 5th International Conference on Polyphenols and Health; 2011

ICPH 2011

Obesity and metabolic syndrome are associated with an inflammatory scenario. Inthe adipose tissue, oxidative stress, activation 01 proinflammatory signaling cascadesand increased adipocytokine production contribute to the pathophysiology 01 thos~conditions. Food extracts with a high content 01 (-)-epicatechin (EC) have beenlound to exert anti-inflammatory actions in adipocytes. This work investigated thecapacity 01 EC to prevent tumor necrosis alpha (TNFalpha)-induced activation 01pro-inflammatory signaling cascades (NF-kB, mitogen activated kinases (MAPKs)ERK1/2, JNK, and p38) and PPARy in adipocytes. 3T3 cells were dilferentiated intoadipocytes and incubated with TNFalpha. NF-kB-, AP-l- and peroxisome proliferator activated receptor gamma (PPARy)-DNA binding was measured by EMSA, and MAPKsphosphorylation by Western blot. Results showed that TNFalpha triggered a time dependent activation of MAPKs, and downstream, of transcription factor AP-l. ECdecreased the phosphorylation levels 01 JNK, ERK1/2, and p-38 in adose (0.5-5~ M)-dependent manner. These elfects were associated with an inhibition of AP-lactivation. TNFalpha also activated the NF-kB signaling cascade, leading to increasedIKK and IkB alpha phosphorylation, p50 nuclear transport, and nuclear NF-kB-DNAbinding. EC inhibited all these increases in the NF-kB activation cascade, with an IC5001 1 ~M. EC attenuated the TNF alpha-mediated suppression of PPARy. In conclusion,EC at concentrations altainable upon consumption 01 flavanol-containing foods, canprevent TNFalpha-mediated triggering ofsignaling cascad es involved in inflammationand insulin resistance. This could be of relevance in the dietary management of thechronic inflammation and insulin resistance associated with obesity and metabolicsyndrome.