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ID 27774
本文ファイル
著者
Nabeshima, Yoshitaka
キーワード
Lipid metabolism
Renin-angiotensin system
Non-alcoholic fatty liver disease
Non-alcoholic steatohepatitis
Peroxisome proliferator-activated receptor alpha
NDC
医学
抄録(英)
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.
掲載誌名
Journal of Hepatology
50巻
6号
開始ページ
1226
終了ページ
1235
出版年月日
2009
出版者
Elsevier Science Bv
ISSN
0168-8278
NCID
出版者DOI
言語
英語
NII資源タイプ
学術雑誌論文
広大資料タイプ
学術雑誌論文
DCMIタイプ
text
フォーマット
application/pdf
著者版フラグ
author
権利情報
Copyright (c) 2009 European Association for the Study of the Liver Published by Elsevier Ireland Ltd.
関連情報URL
部局名
医歯薬学総合研究科