Hepatocytes derived increased SAA1 promotes intrahepatic platelet aggregation and aggravates liver inflammation in NAFLD.

Abstract

Non-alcoholic fatty liver disease (NAFLD) is the pathological manifestation of metabolic syndrome in liver. Its pathological changes may evolve from the initial simple steatosis to non-alcoholic steatohepatitis, liver fibrosis and even liver cancer. Numerous studies have proved that platelets play a vital role in liver disease and homeostasis. Particularly, anti-platelet therapy can reduce intrahepatic platelet aggregation and improve the inflammation of fatty liver. Previous study has also confirmed that SAA is a gene closely related to high-fat diet (HFD) induced obesity, and SAA1 can promote liver insulin resistance induced by Palmitate or HFD. Here, we found that SAA1 treated platelets presented increased sensitivity of platelet aggregation, enhanced activation and increased adhesion ability, and such function was partly dependent on Toll-Like Receptor (TLR) 2 signaling. In addition, blocking SAA1 expression in vivo not only inhibited platelet aggregation in the liver tissues of NAFLD mice, but also alleviated the inflammation of fatty liver. In conclusion, our findings identify that HFD-induced hepatic overexpressed SAA1 aggravates fatty liver inflammation by promoting intrahepatic platelet aggregation, these results also imply that SAA1 may serve as a potential target for ameliorating NAFLD.

• Authors: Daoyuan Li, Ping Xie, Su Zhao, Jing Zhao, Yucheng Yao, Yan Zhao, Guangbing Ren, Xingde Liu
• Journal: Biochemical and biophysical research communications (Biochem Biophys Res Commun) Vol. 555 Pg. 54-60 (05 28 2021) ISSN: 1090-2104 [Electronic] United States
• PMID: 33813276 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2021 Elsevier Inc. All rights reserved.

Chemical References

• Saa2 protein, mouse
• Serum Amyloid A Protein
• Tlr2 protein, mouse
• Toll-Like Receptor 2

Topics

• Animals
• Cell Adhesion (drug effects)
• Diet, High-Fat (adverse effects)
• Female
• Hepatitis (etiology)
• Hepatocytes (metabolism, pathology)
• Humans
• Mice, Inbred BALB C
• Non-alcoholic Fatty Liver Disease (metabolism, physiopathology)
• Platelet Aggregation (drug effects)
• Serum Amyloid A Protein (genetics, metabolism, pharmacology)
• Toll-Like Receptor 2 (metabolism)
• Mice