AMP-activated protein kinase regulates lipid metabolism and the fibrotic phenotype of hepatic stellate cells through inhibition of autophagy

作者：Chen, Ming; Liu, Jiaxing; Yang, Lili^*; Ling, Wenhua^*

来源：FEBS Open Bio, 2017, 7(6): 811-820.

DOI：10.1002/2211-5463.12221

• AMP-activated protein kinase
• autophagy
• hepatic stellate cell
• microtubule-associated protein light chain 3

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 beta (TGF-beta) 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-beta. Pretreatment with the autophagy inducer rapamycin reversed the effects of AMPK, further confirming that AICAR inhibited TGF-beta-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-beta-induced autophagy flux.

• 出版日期2017-6
• 单位中山大学