Green Tea Prevents NAFLD by Modulation of miR-34a and miR-194 Expression in a High-Fat Diet Mouse Model

Figure 6

The proposed mechanism by which green tea acts against NAFLD. The reduction of hepatic lipid accumulation mediated by green tea during NAFLD occurs by a positive and negative regulation of FA oxidation and cholesterol synthesis, respectively. The decrease in miR-34a expression leads to the increase of its targets SIRT1 and PPAR-α, key genes for β-oxidation. High plasma levels of plasma adiponectin combined with the increase of its AdipoR1 and AdipoR2 receptors in the liver contribute to the activation of the AMPK pathway through the increase of PKAβ and AMPKα. Both AMPK and SIRT1 are PGC1α activators. Increasing PGC1α together with increased RXRβ results in increased PPAR-α and δ expression leading to the increase of UCP2 and ACSL3 that coordinate FA catabolism. To increase FA availability during this catabolism, an induction of FoxO1 is medicated by SIRT1/AMPK that results in the increase of ATGL, promoting a higher rate of lipolysis. To avoid ectopic fat accumulation, there is also a lower expression of CD36, avoiding the FA uptake from diet or adipose tissue. The decrease in the inflammatory axis TRL4/TRAF6/NFkB results in the decrease of TNF-α, a negative regulator of miR-194. Thus, hepatic and plasma TNF-α decrease mediates the increase of miR-194 which inhibits ApoA5 expression decreasing the lipid droplet formation, in addition to inhibiting HMGCS. Low expression of miR-34a increases Insig2 expression promoting the degradation of HMGCR. The decrease in HMGCS and HMGCR results in lower cholesterol biosynthesis and accumulation in the liver.