Viburnum opulus L. fruit phenolic compounds protect against FFA-induced steatosis of HepG2 cells via AMPK pathway

Abstract Recent studies indicated phenolic compounds as the substances effectively improving hepatic lipid homeostasis, insulin signaling and mitochondrial functions via decrease of fatty acid uptake and lipogenesis inhibition. The aim of the study was to investigate the Viburnum opulus L. fruits as a dietary source of bioactive phenolic compounds with protective activity against steatosis of HepG2 cells induced by oleic and palmitic acids. Enhanced lipid accumulation (even by 88% after oleic acid treatment) and mitochondrial dysfunctions caused by free fatty acids (FFA) overload were decreased up to 45% by V. opulus preparations compared to cells treated with FFA. Among studied preparations the purified juice had the most significant effect on activation of AMP-activated protein kinase (AMPK). As direct inducers of AMPK were identified liver kinase B1 (LKB1) and allosteric changes caused by decrease of ATP:AMP ratio. Observed signal transduction decreased level of lipogenic proteins - sterol regulatory element-binding protein-1c (SREBP-1c), acetyl-CoA carboxylase (ACC) and fatty acid synthase (FAS). The observed biological activities of V. opulus fruit made this source of phenolic compounds more attractive in terms of health-promoting properties, especially in the context of hepatic lipotoxicity prevention.