In:
Scientific Reports, Springer Science and Business Media LLC, Vol. 7, No. 1 ( 2017-10-02)
Abstract:
Despite the consistent rise of non-alcoholic steatohepatitis (NASH) worldwide, the mechanisms that govern the inflammatory aspect of this disease remain unknown. Previous research showed an association between hepatic inflammation and lysosomal lipid accumulation in blood-derived hepatic macrophages. Additionally, in vitro findings indicated that lipids, specifically derived from the oxidized low-density lipoprotein (oxLDL) particle, are resistant to removal from lysosomes. On this basis, we investigated whether lysosomal lipid accumulation in blood-derived hepatic macrophages is causally linked to hepatic inflammation and assessed to what extent increasing anti-oxLDL IgM autoantibodies can affect this mechanism. By creating a proof-of-concept mouse model, we demonstrate a causal role for lysosomal lipids in blood-derived hepatic macrophages in mediating hepatic inflammation and initiation of fibrosis. Furthermore, our findings show that increasing anti-oxLDL IgM autoantibody levels reduces inflammation. Hence, therapies aimed at improving lipid-induced lysosomal dysfunction and blocking oxLDL-formation deserve further investigation in the context of NASH.
Type of Medium:
Online Resource
ISSN:
2045-2322
DOI:
10.1038/s41598-017-13058-z
Language:
English
Publisher:
Springer Science and Business Media LLC
Publication Date:
2017
detail.hit.zdb_id:
2615211-3