Epigallocatechin gallate (EGCG) is a major polyphenol in green tea which has beneficial effects in prevention of cardiovascular disease. Autophagy is a cellular process that protects cells from stressful conditions. To determine whether beneficial effect of EGCG is mediated by a mechanism involving autophagy, the role of EGCG-stimulated autophagy in the context of ectopic lipid accumulation were investigated. Treatment with EGCG increased formation of LC3-II and autophagosomes in primary bovine aortic endothelial cells (BAEC). Activation of CaMKKβ was required for EGGC-induced LC3-II formation, as evidenced by the fact that EGCG-induced LC3-II formation was significantly impaired by knock-down of CaMKKβ. This effect is most likely due to cytosolic Ca++ load. To determine whether EGCG affects palmitate-induced lipid accumulation, the effects of EGCG on autophagic flux and co-localization of lipid droplets and autophagolysosomes were examined. EGCG normalized the palimitate-induced impairment of autophagic flux. Accumulation of lipid droplets by palmitate was markedly reduced by EGCG. Blocking autophagosomal degradation opposed the effect of EGCG in ectopic lipid accumulation, suggesting the action of EGCG is through autophagosomal degradation. The mechanism for this could be due to the increased co-localization of lipid droplets and autophagolysosome. Co-localization of lipid droplets with LC3 and lysosome was dramatically increased when the cells were treated with EGCG and palmitate compared to the cells treated with palmitate alone. Collectively, the findings suggest that EGCG regulates ectopic lipid accumulation through a facilitated autophagic flux, and further implicate that EGCG may be a potential therapeutic reagent to prevent cardiovascular complications.
Kim HS, Montana V, Jang HJ, Parpura V, Kim JA. Epigallocatechin-gallate (EGCG) stimulates autophagy in vascular endothelial cells: A potential role for reducing lipid accumulation. J Biol Chem. 2013 June University of Alabama at Birmingham, United States;