Abstract
Hepatic stellate cells (HSCs) are the principal hepatic cell type responsible for liver fibrosis. Although AMP-activated protein kinase (AMPK) is known to regulate the activation of HSCs, little is known about its underlying molecular mechanisms. In the present study, we demonstrate that AMPK activation by 5-aminoimidazole-4-carboxamide-1-4-ribofuranoside (AICAR) restricts the fibrotic potential elicited by transforming growth factor β (TGF-β) in LX-2 cells through modulation of autophagy. AICAR treatment activated the mechanistic target of rapamycin/Akt pathway and thus inhibited autophagy flux and lipid droplet degradation in lysosomes induced by TGF-β. Pretreatment with the autophagy inducer rapamycin reversed the effects of AMPK, further confirming that AICAR inhibited TGF-β-induced HSC activation via the regulation of autophagy flux. Our study indicates that AICAR exerts its anti-fibrotic and anti-lipid depletion effect, at least in part, by inhibiting TGF-β-induced autophagy flux.