The Arachidonic Acid Metabolome Serves as a Conserved Regulator of Cholesterol Metabolism

DOI HANDLE HANDLE HANDLE Web Site ほか2件をすべて表示 一部だけ表示 参考文献43件 オープンアクセス

書誌事項

公開日
2014-11
資源種別
journal article
権利情報
  • https://www.elsevier.com/tdm/userlicense/1.0/
  • http://creativecommons.org/licenses/by/3.0/
DOI
  • 10.1016/j.cmet.2014.09.004
公開者
Elsevier BV

この論文をさがす

説明

Cholesterol metabolism is closely interrelated with cardiovascular disease in humans. Dietary supplementation with omega-6 polyunsaturated fatty acids including arachidonic acid (AA) was shown to favorably affect plasma LDL-C and HDL-C. However, the underlying mechanisms are poorly understood. By combining data from a GWAS screening in100,000 individuals of European ancestry, mediator lipidomics, and functional validation studies in mice, we identify the AA metabolome as an important regulator of cholesterol homeostasis. Pharmacological modulation of AA metabolism by aspirin induced hepatic generation of leukotrienes (LTs) and lipoxins (LXs), thereby increasing hepatic expression of the bile salt export pump Abcb11. Induction of Abcb11 translated in enhanced reverse cholesterol transport, one key function of HDL. Further characterization of the bioactive AA-derivatives identified LX mimetics to lower plasma LDL-C. Our results define the AA metabolomeasconserved regulator of cholesterol metabolism, and identify AA derivatives as promising therapeutics to treat cardiovascular disease in humans.

収録刊行物

参考文献 (43)*注記

もっと見る

関連プロジェクト

もっと見る

キーワード

問題の指摘

ページトップへ