In:
Liver International, Wiley, Vol. 33, No. 7 ( 2013-08), p. 1056-1061
Kurzfassung:
Non‐alcoholic steatohepatitis ( NASH ) is characterized by steatosis and inflammation. The transition from steatosis towards NASH represents a key step in pathogenesis, as it will set the stage for further severe liver damage. Under normal conditions, lipoproteins that are endocytosed by K upffer cells ( KC s) are easily transferred from the lysosomes into the cytoplasm. Oxidized LDL (ox LDL ) that is taken up by the macrophages in vitro is trapped within the lysosomes, while acetylated LDL (ac LDL ) is leading to normal lysosomal hydrolysis, resulting in cytoplasmic storage. We have recently demonstrated that hepatic inflammation is correlated with lysosomal trapping of lipids. So far, a link between lysosomal trapping of ox LDL and inflammation was not established. We hypothesized that lysosomal trapping of ox LDL in KC s will lead to hepatic inflammation. Methods Ldlr −/− mice were injected with LDL , ac LDL and ox LDL and sacrificed after 2, 6 and 24 h. Results Electron microscopy of KC s demonstrated that after ox LDL injection, small lipid inclusions were present inside the lysosomes after all time points and were mostly pronounced after 6 and 24 h. In contrast, no lipid inclusions were present inside KC s after LDL or ac LDL injection. Hepatic expression of several inflammatory genes and scavenger receptors was higher after ox LDL injections compared with LDL or ac LDL . Conclusions These data suggest that trapping of ox LDL inside lysosomes of KC s in vivo is causally linked to increased hepatic inflammatory gene expression. Our novel observations provide new bases for prevention and treatment of NASH .
Materialart:
Online-Ressource
ISSN:
1478-3223
,
1478-3231
DOI:
10.1111/liv.2013.33.issue-7
Sprache:
Englisch
Verlag:
Wiley
Publikationsdatum:
2013
ZDB Id:
2124684-1
