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Because PPAR alpha is a central regulator of triglyceride homeostasis and mediates hepatocarcinogenesis in rodents, we determined whether PPAR alpha contributes to HCV core protein-induced diseases. We generated PPAR alpha-homozygous, -heterozygous, and -null mice with liver-specific transgenic expression of the core protein gene (Ppara(+/+):HCVcpTg, Ppara(-/-):HCVcpTg, and Ppara(-/-):HCVcpTg mice. Severe steatosis was unexpectedly observed only in Ppara+/+:HCVcpTg mice, which resulted from enhanced fatty acid uptake and decreased mitochondrial beta-oxidation due to breakdown of mitochondrial outer membranes. Interestingly, HCC developed in approximately 35% of 24-month-old Pparat(+/+): HCVcpTg mice, but tumors were not observed in the other genotypes. These phenomena were found to be closely associated with sustained PPAR alpha activation. In Ppara(+/-):HCVcpTg mice, PPAR alpha activation and the related changes did not occur despite the presence of a functional Ppara allele. However, long-term treatment of these mice with clofibrate, a PPAR alpha activator, induced HCC with mitochondrial abnormalities and hepatic steatosis. 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  1. 050 医学部, 大学院医学系研究科
  2. 0501 学術論文

PPAR alpha activation is essential for HCV core protein-induced hepatic steatosis and hepatocellular carcinoma in mice

http://hdl.handle.net/10091/1161
http://hdl.handle.net/10091/1161
bed9b14f-0b32-4123-8a31-09f1b2fd8295
名前 / ファイル ライセンス アクション
33594RG-RV2[1].pdf 33594RG-RV2[1].pdf (220.9 kB)
Item type 学術雑誌論文 / Journal Article(1)
公開日 2008-09-18
タイトル
言語 en
タイトル PPAR alpha activation is essential for HCV core protein-induced hepatic steatosis and hepatocellular carcinoma in mice
言語
言語 eng
資源タイプ
資源 http://purl.org/coar/resource_type/c_6501
タイプ journal article
著者 Tanaka, N

× Tanaka, N

WEKO 8313

en Tanaka, N

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Moriya, K

× Moriya, K

WEKO 8314

en Moriya, K

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Kiyosawa, K

× Kiyosawa, K

WEKO 8315

en Kiyosawa, K

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Koike, K

× Koike, K

WEKO 8316

en Koike, K

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Gonzalez, FJ

× Gonzalez, FJ

WEKO 8317

en Gonzalez, FJ

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Aoyama, T

× Aoyama, T

WEKO 8318

en Aoyama, T

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出版者
出版者 AMER SOC CLINICAL INVESTIGATION INC
引用
内容記述タイプ Other
内容記述 JOURNAL OF CLINICAL INVESTIGATION. 118(2):683-694(2008)
書誌情報 JOURNAL OF CLINICAL INVESTIGATION

巻 118, 号 2, p. 683-694, 発行日 2008-02
資源タイプ(コンテンツの種類)
内容記述タイプ Other
内容記述 Article
ISSN
収録物識別子タイプ PISSN
収録物識別子 0021-9738
書誌レコードID
収録物識別子タイプ NCID
収録物識別子 AA00695520
DOI
識別子タイプ DOI
関連識別子 https://doi.org/10.1172/JCI33594
関連名称 10.1172/JCI33594
出版タイプ
出版タイプ AM
出版タイプResource http://purl.org/coar/version/c_ab4af688f83e57aa
WoS
表示名 Web of Science
URL http://gateway.isiknowledge.com/gateway/Gateway.cgi?&GWVersion=2&SrcAuth=ShinshuUniv&SrcApp=ShinshuUniv&DestLinkType=FullRecord&DestApp=WOS&KeyUT=000252777400035
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