AMP ‐activated protein kinase regulates lipid metabolism and the fibrotic phenotype of hepatic stellate cells through inhibition of autophagy
Year: 2017
Type: article
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.
Source: FEBS Open Bio
Authors: Ming Chen, Jiaxing Liu, Lili Yang, Wenhua Ling
Institutions: Sun Yat-sen University, Key Laboratory of Guangdong Province
Language: English
Subfield: Hepatology
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $2,210
OpenAlex ID: W2604648317