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An Approach to Improve Intestinal Absorption of Poorly Absorbed Water-Insoluble Components via Niemann Pick C1-Like 1

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Title: An Approach to Improve Intestinal Absorption of Poorly Absorbed Water-Insoluble Components via Niemann Pick C1-Like 1
Authors: Takekawa, Yuto Browse this author
Sato, Yuki Browse this author →KAKEN DB
Yamaki, Yoshiaki Browse this author
Imai, Mei Browse this author
Noto, Kazuma Browse this author
Sumi, Masato Browse this author →KAKEN DB
Takekuma, Yoh Browse this author →KAKEN DB
Iseki, Ken Browse this author →KAKEN DB
Sugawara, Mitsuru Browse this author →KAKEN DB
Keywords: Niemann Pick C1-Like 1
absorption
cholesterol
emulsion
coenzyme Q10
Issue Date: Mar-2016
Publisher: The Pharmaceutical Society of Japan
Journal Title: Biological & pharmaceutical bulletin
Volume: 39
Issue: 3
Start Page: 301
End Page: 307
Publisher DOI: 10.1248/bpb.b15-00359
PMID: 26934923
Abstract: Dietary and biliary cholesterol absorption contributes to the maintenance of tight control of cholesterol homeostasis. Cholesterol is present as mixed micelles formed by bile salts and phospholipids in the intestinal lumen. Recently, Niemann Pick Cl-Like 1 (NPC1L1) transporter was identified as being critical for cholesterol absorption. However, the uptake mechanism of an enveloped substrate of NPC1L1 in whole lipid emulsion particles remains unclear. In this study, we investigated the uptake mechanism of a substrate of NPC1L1 in lipid emulsion particles. We also investigated whether these particles containing cholesterol can improve the intestinal absorption of other lipophilic components via NPC1L1. The uptake of lysophosphatidylcholine (LPC)-4,4-difluoro-5-(4-phenyl-1,3-butadienyl)-4-bora-3a,4a-diaza-s-indacene-3-propionic acid saccinimidyl ester (BODIPY), a fluorescently labeled phospholipid, in lipid emulsion particles containing cholesterol (1 mu m) was significantly increased compared to that without cholesterol in Caco-2 cells. On the other hand, its increased uptake was significantly inhibited by ezetimibe, a selective inhibitor of NPC1L1. These results suggested that not only cholesterol but also some components in lipid emulsion particles are taken up into enterocytes via NPC1L1. We also examined an approach to improve intestinal absorption of a poorly absorbed water-insoluble component, coenzyme Q10 (CoQ10), by this mechanism. The uptake of CoQ10 in lipid emulsion particles containing cholesterol was significantly increased compared to that without cholesterol. Its increased uptake was significantly inhibited by ezetimibe. Though it is still not clear whether CoQ10 is a substrate of NPC1L1, there is a potential for improvement of the absorption of poorly absorbed components by lipid emulsion particles containing cholesterol.
Type: article
URI: http://hdl.handle.net/2115/61283
Appears in Collections:薬学研究院 (Faculty of Pharmaceutical Sciences) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)

Submitter: 菅原 満

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