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
Zinc-α2-glycoprotein 1 (AZGP1) plays important roles in metabolism-related diseases. The underlying molecular mechanisms and therapeutic effects of AZGP1 remain unknown in non-alcoholic fatty liver disease (NAFLD).
To explore the effects and potential mechanism of AZGP1 on NAFLD in vivo and in vitro.
The expression of AZGP1 and its effects on hepatocytes were examined in NAFLD patients, CCl4-treated mice fed a high fat diet (HFD), and human LO2 cells.
AZGP1 levels were significantly decreased in liver tissues of NAFLD patients and mice. AZGP1 knockdown was found to activate inflammation; enhance steatogenesis, including promoting lipogenesis [sterol regulatory element-binding protein (SREBP)-1c, liver X receptor (LXR), fatty acid synthase (FAS), acetyl-CoA carboxylase (ACC), and stearoyl CoA desaturase 1 (SCD)-1], increasing lipid transport and accumulation [fatty acid transport protein (FATP), carnitine palmitoyl transferase (CPT)-1A, and adiponectin], and reducing fatty acid β-oxidation [farnesoid X receptor (FXR) and peroxisome proliferator-activated receptor (PPAR)-α]; accelerate proliferation; and reverse apoptosis in LO2 cells. AZGP1 overexpression (OV-AZGP1) had the opposite effects. Furthermore, AZGP1 alleviated 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 dramatically improved liver injury and eliminated liver fat in NAFLD mice.
AZGP1 attenuates NAFLD with regard to ameliorating inflammation, accelerating lipolysis, promoting proliferation, and reducing apoptosis by negatively regulating TNF-α. AZGP1 is suggested to be a novel promising therapeutic target for NAFLD.
Core tip: The expression of zinc-α2-glycoprotein 1 (AZGP1) was significantly down-regulated in liver tissues of non-alcoholic fatty liver disease (NAFLD) patients and mice. In LO2 cells, AZGP1 had the effects of alleviating NAFLD by means of blocking tumour necrosis factor-α signalling mediated inflammation and intracellular lipid deposition, promoting proliferation, and inhibiting apoptosis. AZGP1 treatment could attenuate NAFLD to some extent in mice. Therefore, AZGP1 is suggested to be a novel promising therapeutic target for NAFLD.