The hop chalcone xanthohumol beneficially affects hepatocellular lipid metabolism

Since ancient times, hop (Humulus lupulus L.) has been used in folkloric medicine. Xanthohumol (XN) is the main flavonoid found in hop inflorescences, and dietary intake is up to 100mg/day, largely depending on beer consumption. Furthermore, XN-containing dietary supplements are marketed, and we recently demonstrated that XN exhibits anti-fibrogenic effects on hepatic stellate cells and anti-tumorigenic effects on HCC cells, respectively. Little is known about the effects of XN on (hepatic) metabolisms. The aim of this study was to analyze the effects of XN on hepatocellular lipid metabolism. Methods and Results: Incubation with free fatty acids (FFA) led to a dose-dependent increase of lipid accumulation in primary human hepatocytes (PHH) as assessed by analysis of cellular triglyceride (TG) and FFA levels and as visualized by oil-red-O staining. This induced lipid accumulation as well as basal lipid levels were dose-dependently inhibited by pretreatment of PHH with XN (5, 10 and 15µM). At the concentrations used viability and mitochondrial activity were not impaired. The expression of fatty acid synthase, the key enzyme of lipogenesis as well as diglyceride acyltransferase, the enzyme responsible for the last step in TG synthesis, were impaired by XN. Moreover, XN affected palmitoyl-CoA oxidase and carnitine palmitoyltransferase 1 expression, indicative of impaired beta-oxidation. Conclusion: Together these data indicate the potential of XN to beneficially affect pathophysiological key mechanisms of nonalcoholic fatty liver disease (NAFLD). Thus, based on the known safety profile of hop extracts and XN, respectively, this hop constituent may safe as a potential new agent to prevent NAFLD development and progression.