Published online Sep 28, 2019. doi: 10.3748/wjg.v25.i36.5451
Peer-review started: June 20, 2019
First decision: July 22, 2019
Revised: July 26, 2019
Accepted: August 24, 2019
Article in press: August 24, 2019
Published online: September 28, 2019
Non-alcoholic fatty liver disease (NAFLD) is increasingly threatening people's health. Zinc-α2-glycoprotein 1 (AZGP1) was originally considered as a potential tumor marker, but subsequent studies have shown that it is also expressed in the liver, heart, lungs, and prostate. AZGP1 plays an important role in metabolism-related diseases, but the specific pathogenesis and therapeutic effects of AZGP1 in NAFLD remain uncertain.
Our findings will provide a basis for the application of AZGP1 in the therapy of NAFLD.
To examine the expression of AZGP1 in NAFLD patients, CCl4-treated mice fed a high fat diet (HFD), and human LO2 cells, and explore biological functions and potential mechanisms of AZGP1 in NAFLD.
We detected the expression of AZGP1 in the liver tissues of NAFLD patients and CCl4-treated mice fed an HFD and human LO2 cells by qPCR and Western blot. The effects of AZGP1 on hepatocytes in vitro and in vivo were then assessed by overexpression and knockdown of AZGP1 in human LO2 cells and in an NAFLD mouse model. In further molecular mechanism research, LO2 cells were treated with sh-AZGP1 or combination of sh-AZGP1 and sh-TNF-α, OV-AZGP1 or combination of OV-AZGP1, and OV-TNF-α to investigate the specific effects of AZGP1 in vitro.
In the current study, we found that AZGP1 was significantly decreased in liver tissues from both humans and mice. Loss of AZGP1 activated inflammation, enhanced steatogenesis, increased lipid transport and accumulation, decreased fatty acid β-oxidation, promoted proliferation, and inhibited apoptosis in human LO2 cells. Over-expression of AZGP1 played an opposite role. In addition, AZGP1 attenuated NAFLD by blocking TNF-α-mediated inflammation and intracellular lipid deposition, promoting proliferation, and inhibiting apoptosis in LO2 cells. Finally, treatment with OV-AZGP1 plasmid in NAFLD mice significantly ameliorated liver damage and eliminated liver fat.
AZGP1 is down-regulated in NAFLD, which could inhibit inflammation, accelerate lipolysis, accelerate proliferation, and reduce apoptosis via suppressing TNF-α. AZGP1 exerts a protective role against NAFLD.
This study provides new insight into the role of AZGP1 in relieving NAFLD by down-relating TNF-α. AZGP1 might be a potential therapeutic approach to prevent and treat NAFLD.