CONICET | Buscador de Institutos y Recursos Humanos

Obesity and metabolic syndrome are associated with an inflammatory scenario. In the adipose tissue, oxidative stress, activation of proinflammatory signaling cascades, and increased adipocytokine production contribute to the pathophysiology of those conditions. Food extracts with a high content of (-)-epicatechin (EC) have been found to exert anti-inflammatory actions in adipocytes. To investigate the capacity of EC to prevent tumor necrosis alpha (TNFá)-induced activation of pro-inflammatory signaling cascades (NF-êB, mitogen activated kinases (MAPKs) ERK1/2, JNK, and p38) and PPARã in adipocytes. 3T3 cells were differentiated into adipocytes and incubated with TNFá. NF-êB-, AP-1- and peroxisome proliferatoractivated receptor ã (PPARã)-DNA binding was measured by EMSA, and MAPKs phosphorylation by Western blot. The results obtained in differentiated adipocytes show that TNFá triggered a time-dependent activation of MAPKs and downstream, of the transcription factor AP-1. EC decreased the phosphorylation levels of JNK, ERK1/2, and p-38 in a dose (0.5-5 µM)-dependent manner. These effects were associated with an inhibition of AP-1 activation. TNFá also activated the NF-êB signaling cascade, leading to increased IKK and IêBá phosphorylation, p50 nuclear transport, and nuclear NF-êB-DNA binding. EC inhibited all these increases in the NF-êB activation cascade, with an IC50 of 1 µM. EC attenuated the TNFá-mediated suppression of PPARã. In conclusion, EC at concentrations attainable upon consumption of flavanol-containing foods, can prevent TNFá-mediated triggering of signaling cascades involved in inflammation and insulin resistance. This could be of relevance in the dietary management of the chronic inflammation and insulin resistance associated with obesity and metabolic syndrome.