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ID 27774
file
creator
Nabeshima, Yoshitaka
subject
Lipid metabolism
Renin-angiotensin system
Non-alcoholic fatty liver disease
Non-alcoholic steatohepatitis
Peroxisome proliferator-activated receptor alpha
NDC
Medical sciences
abstract
Background/Aims: A distinct subgroup of angiotensin II type I receptor (AT1R) blockers (ARBs) have been reported to suppress the development of hepatic steatosis. These effects were generally explained by selective peroxisome proliferator-activated receptor (PPAR) gamma modulating properties of ARBs, independent of their AT1R blocking actions. Here, we provide genetic evidence of the direct role for AT1R in hepatic steatosis. Methods: The effect of AT1R deletion on steatohepatitis was investigated in AT1a(-/-) mice. Furthermore, the influence of AT1R inhibition by telmisartan as well as gene silencing of AT1R by siRNA was assessed in an in vitro experiment using HepG2 cells. Results: Compared to wild-type (WT), A T1a(-/-) mice fed methionine-choline deficient (MCD) diet resulted in negligible lipid accumulation in the liver with marked induction of PPAR alpha mRNA. In vitro experiments also demonstrated reduced cellular lipid accumulation by telmisartan and AT1R knockdown following exposure of long chain fatty acids. This is pre-sumably explained by the observation that the expression of PPAR alpha and its target genes were significantly up-regulated in specific siRNA treated HepG2 cells. Conclusions: Our data indicate, in addition to pharmacological effect of ARBs on PPAR gamma activation, a key biological role for AT1R in the regulation of hepatic lipid metabolism.
journal title
Journal of Hepatology
volume
Volume 50
issue
Issue 6
start page
1226
end page
1235
date of issued
2009
publisher
Elsevier Science Bv
issn
0168-8278
ncid
publisher doi
language
eng
nii type
Journal Article
HU type
Journal Articles
DCMI type
text
format
application/pdf
text version
author
rights
Copyright (c) 2009 European Association for the Study of the Liver Published by Elsevier Ireland Ltd.
relation url
department
Graduate School of Biomedical Science