There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.
Abstract
Baicalein has been proved as a promising compound for non-alcoholic fatty liver disease
(NAFLD); however, the molecular mechanisms underlying the progression of NAFLD and
its intervention by baicalein remain largely obscure. Male C57BL/6J fed high-fat diet
(HFD) and HepG2 cells stimulated with free fatty acid were treated with baicalein
and various pharmacological reagents to explore the effect of signaling pathways involved
in lysosomal acidification. Baicalein intake declined ALT and AST activities by 25.1%
and 18.7%, respectively, compared with the HFD group. Moreover, baicalein markedly
ameliorated the HFD-trigged lysosomal membrane permeabilization evidenced by declined
cathepsin B release. Subsequent disorders, including cathepsin D maturation and mitochondrion
membrane potential were also partially normalized by baicalein administration to HFD-fed
mice. Meanwhile, an increase in V-ATPase V1 subunits expression in lysosomes, V-ATPase
activity and the colocalization of cytosol V-ATPase V1 subunits and lysosomes was
observed in baicalein-supplement mice. Bafilomycin A1 stimulation resulting in elevated
lysosomal pH and triacylglycerol accumulation partially abolished the effect of baicalein.
Furthermore, incubation with mTOR inhibitor rapamycin restored lysosomal pH and decreased
cellular triacylglycerol content. Collectively, these findings demonstrate that hepatic
lysosomal acidification is the main target of baicalein against NAFLD via maintaining
lysosomal V-ATPase assembly through mTOR pathway.