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

Increasing evidence indicates that several mechanisms, associated or not with antioxidant actions, are involved in the effects of flavonoids on health. Flavonoid-rich beverages, foods, and extracts, as well as pure flavonoids are studied for the prevention and/or amelioration of metabolic syndrome (MS) and MS-associated diseases. We summarize evidence linking flavonoid consumption with the risk factors defining MS: obesity, hypertriglyceridemia, hypercholesterolemia, hypertension, and insulin resistance. Nevertheless, a number of molecular mechanisms have been identified; the effects of flavonoids modifying major endpoints of MS are still inconclusive. These difficulties are explained by the complex relationships among the risk factors defining MS, the multiple biological targets controlling these risk factors, and the high number of flavonoids (including their metabolites) present in the diet and potentially responsible for the in vivo effects. Consequently, extensive basic and clinical research is warranted to assess the final relevance of flavonoids for MS.

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