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VLCAD deficiency is associated with the accumulation of fat in multiple organs and tissues, which results in specific clinical features including cardiomyopathy, cardiomegaly, muscle weakness, and hepatic dysfunction in infants. We speculated that the abnormal fatty acid metabolism in VLCAD-deficient individuals might cause cell necrosis by fatty acid toxicity. The accumulation of fatty acids may activate peroxisome proliferator-activated receptor (PPAR), a master regulator of fatty acid metabolism and a potent nuclear receptor for free fatty acids. We examined six skin fibroblast lines, derived from VLCAD-deficient patients and identified fatty acid accumulation and PPAR alpha activation in these cell lines. We then found that the expression levels of three enzymes involved in fatty acid degradation, including long-chain acyl-CoA synthetase (LACS), were increased in a PPAR alpha-dependent manner. This increased expression of LACS might enhance the fatty acyl-CoA supply to fatty acid degradation and sulfatide synthesis pathways. In fact, the first and last reactions in the sulfatide synthesis pathway are regulated by PPAR alpha. Therefore, we also measured the expression levels of enzymes involved in sulfatide metabolism and the regulation of cellular sulfatide content. The levels of these enzymes and cellular sulfatide content both increased in a PPAR alpha-dependent manner. 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Activation of PPARα by Fatty Acid Accumulation Enhances Fatty Acid Degradation and Sulfatide Synthesis(脂肪酸蓄積によるPPARα活性化は脂肪酸分解とスルファチド合成を促進する)
http://hdl.handle.net/10091/00019726
f74d9983-8796-4a1d-b4b1-75a0ce777a9f
名前 / ファイル | ライセンス | アクション | |
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Item type | 学位論文 / Thesis or Dissertation(1) | |||||
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公開日 | 2017-06-06 | |||||
タイトル | ||||||
言語 | en | |||||
タイトル | Activation of PPARα by Fatty Acid Accumulation Enhances Fatty Acid Degradation and Sulfatide Synthesis(脂肪酸蓄積によるPPARα活性化は脂肪酸分解とスルファチド合成を促進する) | |||||
言語 | ||||||
言語 | eng | |||||
資源タイプ | ||||||
資源 | http://purl.org/coar/resource_type/c_db06 | |||||
タイプ | doctoral thesis | |||||
著者 |
封, 玉瑶
× 封, 玉瑶 |
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出版者 | ||||||
出版者 | 信州大学 | |||||
引用 | ||||||
内容記述タイプ | Other | |||||
内容記述 | 封 玉瑶. Activation of PPARα by Fatty Acid Accumulation Enhances Fatty Acid Degradation and Sulfatide Synthesis(脂肪酸蓄積によるPPARα活性化は脂肪酸分解とスルファチド合成を促進する). 信州大学, 2016, 博士論文. | |||||
書誌情報 |
発行日 2016-03-31 |
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学位授与番号 | ||||||
学位授与番号 | 13601甲第1064号 | |||||
学位授与年月日 | ||||||
学位授与年月日 | 2016-03-31 | |||||
学位名 | ||||||
学位名 | 博士(医学) | |||||
学位授与機関 | ||||||
学位授与機関名 | ||||||
学位授与機関名 | 信州大学(Shinshu university) | |||||
学位の区分 | ||||||
Doctoral | ||||||
学位の分野 | ||||||
医学 | ||||||
学位の報告番号 | ||||||
甲第1064号 | ||||||
内容記述 | ||||||
内容記述タイプ | Other | |||||
内容記述 | 雑誌に発表。TOHOKU JOURNAL OF EXPERIMENTAL MEDICINE. 240(2):113-122 (2016); doi:10.1620/tjem.240.113. | |||||
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 | Thesis | |||||
PubMed | ||||||
関連識別子 | ||||||
識別子タイプ | PMID | |||||
関連識別子 | http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?CMD=search&DB=pubmed&term=27644403 | |||||
関連名称 | ||||||
関連名称 | 27644403 | |||||
DOI | ||||||
関連識別子 | ||||||
識別子タイプ | DOI | |||||
関連識別子 | https://doi.org/10.1620/tjem.240.113 | |||||
関連名称 | ||||||
関連名称 | 10.1620/tjem.240.113 | |||||
権利 | ||||||
権利情報 | © 2016 Tohoku University Medical Press | |||||
出版タイプ | ||||||
出版タイプ | NA | |||||
出版タイプResource | http://purl.org/coar/version/c_be7fb7dd8ff6fe43 | |||||
WoS | ||||||
Web of Science | ||||||
URL | http://gateway.isiknowledge.com/gateway/Gateway.cgi?&GWVersion=2&SrcAuth=ShinshuUniv&SrcApp=ShinshuUniv&DestLinkType=FullRecord&DestApp=WOS&KeyUT=000386641700003 |