Transport via Niemann-Pick C1 Like 1 contributes to the intestinal absorption of ubiquinone

• Nashimoto, Shunsuke

• Takekawa, Yuto

• Takekuma, Yoh

• Sugawara, Mitsuru

• Sato, Yuki

Abstract

Ubiquinone, which is a component in the electron-transport systems of mitochondria, is essential for various activities related to energy metabolism, but the detailed absorption mechanism of ubiquinone is not clear. On the other hand, Niemann-Pick C1 Like 1 (NPC1L1) is involved in the intestinal absorption of fat-soluble components such as cholesterol. In this study, we investigated whether the intestinal absorption of ubiquinone was transported by NPC1L1 as is cholesterol. In this study, coenzyme q10 (CoQ10) and coenzyme q9 (CoQ9) were used as models of ubiquinone. The transport activity of ubiquinone was increased significantly in NPC1L1-overexpressed Madin-Darby canine kidney (MDCK) cells compared with that in pMAM2-BSD vector-transfected MDCK cells and the uptake of ubiquinone was decreased in the presence of ezetimibe, an inhibitor of NPC1L1. These results indicate that NPC1L1 mediates the transport of ubiquinone. Furthermore, to clarify the effect of NPC1L1 on the intestinal absorption of CoQ10, emulsified CoQ10 was orally administered to Wistar rats, and the plasma concentration was measured. The plasma concentration of CoQ10 was significantly decreased by coadministration of ezetimibe and CoQ10 compared to that with administration of only CoQ10. This result indicates that the intestinal absorption of CoQ10 is mediated by NPC1L1. (C) 2020 The Japanese Society for the Study of Xenobiotics. Published by Elsevier Ltd. All rights reserved.

Journal

• Drug metabolism and pharmacokinetics

  Drug metabolism and pharmacokinetics 35 (6), 527-533, 2020-12

  Japanese Society for the Study of Xenobiotics（日本薬物動態学会）JSSX

Keywords

• Coenzyme Q10 (PubChem CID: 5281915)
• Coenzyme Q9 (PubChem CID: 5280473)
• Niemann-pick C1 like 1
• Ezetimibe
• Intestinal absorption
• Mixed micelle

Details

• CRID: 1050009295015128832
• NII Article ID: 120007181817
• DOI: 10.1016/j.dmpk.2020.08.002
• HANDLE: 2115/83758
• ISSN: 13474367
• Web Site: https://api.elsevier.com/content/article/PII:S1347436720304067?httpAccept=text/xml
• Web Site: https://api.elsevier.com/content/article/PII:S1347436720304067?httpAccept=text/plain
• Web Site: https://search.jamas.or.jp/link/ui/2021296794
• Text Lang: en
• Article Type: journal article
• Data Source:
  • IRDB
  • Crossref
  • CiNii Articles
  • KAKEN