Epidemiological studies have shown that coffee consumption may be associated with a lower risk of developing several chronic disorders. To elucidate the molecular mechanism of the effects of coffee, we analyzed molecular response upon exposure to coffee extract using cellular and animal models of these diseases. As obesity is recognized as a major risk factor for these chronic diseases, we investigated the effect of coffee on adipogenesis using mouse preadipocyte 3T3-L1 cells. We found that coffee induced proteasomal degradation of IRS-1, leading to reduction of PPARγ expression, a master transcription factor for adipogenesis. Reduction in weight as well as in IRS-1 expression was detected in the fat tissues of the high fat-diet-fed mice when reared with 60% coffee for 7 weeks. As for Alzheimer's disease, we analyzed the effect of coffee on amyloid β (Aβ) production in human neuronal SH-SY5Y cells. We found a 20% reduction in Aβ production when treated with 2.5% coffee for 2 d. This reduction was due to proteasomal degradation of BACE1 (β-secretase), which was activated by protein kinase A. In addition, coffee ameliorates LPS-induced inflammatory responses in RAW264.7 macrophages by reducing NFκB activity and Nrf2 activation. Roasted coffee prevents selenite-induced cataractogenesis by ameliorating antioxidant loss. Pyrocatechol, a component of roasted coffee, also reduced Aβ production and exhibits anti-inflammatory effects by a similar mechanism as coffee. Our results suggest that roasting coffee beans to generate pyrocatechol is necessary for the preventive effects of coffee intake on the chronic diseases.
Keywords: Alzheimer's disease; cataract; coffee; inflammation; obesity; pyrocatechol.