Z Gastroenterol 2015; 53 - A3_33
DOI: 10.1055/s-0035-1568053

The platelet-derived chemokine CXCL4 exerts protective role in non-alcoholic steatohepatitis (NASH) in vivo

HK Drescher 1, C Berger 1, P Fischer 1, ML Berres 1, DC Kroy 1, KL Streetz 1, C Trautwein 1, H Sahin 1
  • 1University Hospital Aachen, Department of Medicine III, Aachen, Germany

Introduction: Non-alcoholic steatohepatitis (NASH) is the third most common reason for liver transplantations in developing countries and one of the fastest growing medical problems.

Aim: It is known that platelets are involved in non-alcoholic fatty liver disease. The significance of CXCL4, one of the most abundant chemokines in platelets, in NASH development and progression remains unclear. We therefore investigated the role of CXCL4, also known as platelet factor 4 (PF4), in a high fat (HF) induced NASH mouse model.

Methods: Constitutive CXCL4 knockout mice were fed HF-diet for 14 weeks.

Results: After 14 weeks of HF treatment CXCL4 deficient animals showed a significantly increased bodyweight and elevated leptin mRNA expression levels indicating the occurrence of the metabolic syndrome compared to WT controls. Consistent with this KO mice displayed massive fatty liver degeneration with more pronounced histomorphological changes and a significantly increased hepatic triglyceride and cholesterol content. The severe NASH progression was further reflected by higher serum transaminase levels and stronger hepatic infiltration of different types of immune cells. Especially t cells, neutrophils and inflammatory macrophages were increased in livers of mice lacking CXCL4 compared to controls. Similar results could be found when analysing the immune cell infiltration in epididymal white adipose tissue (eWAT). Namely higher numbers of different t cell populations and neutrophils in CXCL4 KO mice. Those inflammatory changes finally resulted in a worsened glucose tolerance as it occurs in human obesity and type 2 diabetes.

Conclusion: CXCL4 has a protective function in HF induced fatty liver disease since a deficiency for this chemokine resulted in faster and stronger development of diet induced NASH. Therefore PF4 provides a potential therapeutic agent for the intervention during steatohepatitis development and progression.

Corresponding author: Drescher, Hannah K

E-Mail: hdrescher@ukaachen.de