Niemann-Pick C1-Like 1 Mediates α-Tocopherol Transport

Narushima, Kazuya; Takada, Tappei; Yamanashi, Yoshihide; Suzuki, Hiroshi

doi:10.1124/mol.107.043034

Cited by 134 publications

(120 citation statements)

References 27 publications

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“…Elle est incorporee dans les micelles mixtes issues de la digestion des lipides et est absorbee dans le duodenum. Les transporteurs scavenger receptor type B1 (SR-B1) (Reboul et al, 2006) et Niemann-Pick C1-like 1 (NPC1L1) (Narushima et al, 2008) sont impliques dans cette absorption. Il est admis que la vitamine E est incorporee sous forme libre dans les chylomicrons.…”

Section: Absorption Et Metabolisation De La Vitamine Eunclassified

Vitamine E et physiologie du tissu adipeux

Landrier

2011

OCL

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Section: Absorption Et Metabolisation De La Vitamine Eunclassified

Vitamine E et physiologie du tissu adipeux

Landrier

2011

OCL

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“…These results suggest that CoQ10 may be a substrate of NPC1L1 as is the case for vitamin E. Although NPC1L1 is known to be a sterol transporter in the intestine, NPC1L1-overexpression appears to facilitate the accumulation of α-tocopherol, which does not have a sterol structure, in an ezetimibe-sensitive manner. 5,14) Abuasal et al reported that the intestinal absorption of γ-tocotrienol is partly mediated by NPC1L1. 23) We also reported that NPC1L1 is partly involved in the absorption of lutein, a dihydroxycarotenoid.…”

Section: Effect Of Cholesterol In Lipid Emulsion Particles On the Uptmentioning

confidence: 99%

“…However, not only cholesterol but also other lipophilic molecules such as vitamin E and lutein have been recently reported to be solubilized in lipid emulsion particles and then partly absorbed in the intestine via NPC1L1. 5,6) NPC1L1 has been predicted to incorporate cholesterol and other parts of lipophilic molecules from mixed micelles into enterocytes via clathrin-mediated endocytosis. 7,8) As just described, the intestinal uptake mechanism of substrates of NPC1L1 has been gradually demonstrated.…”

mentioning

confidence: 99%

An Approach to Improve Intestinal Absorption of Poorly Absorbed Water-Insoluble Components <i>via</i> Niemann–Pick C1-Like 1

Takekawa

Sato

Yamaki

et al. 2016

Biological & Pharmaceutical Bulletin

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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 C1-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 µM) 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.Key words Niemann-Pick C1-Like 1; absorption; cholesterol; emulsion; coenzyme Q10Intestinal absorption is an important process in the maintenance of homeostasis in the body. Cholesterol homeostasis is a highly regulated balance of de novo synthesis, dietary cholesterol absorption, and biliary clearance and excretion. Although the cholesterol uptake mechanism in the intestinal lumen is not fully understood, the identification of ezetimibe as a selective inhibitor of intestinal cholesterol absorption suggested that these processes are mediated by a specific transport system rather than by passive diffusion.1) In 2004, Altmann et al. identified Niemann-Pick C1-Like 1 (NPC1L1) as an apically localized sterol transporter in the small intestine.2) NPC1L1 is highly expressed in the small intestine, particularly in the upper intestine.2,3) NPC1L1 protein has 13 predicted transmembrane domains and extensive N-linked glycosylation sites located within the extracellular loops and it contains a sterol sensing domain (SSD).4) It has predicted that the substrates of NPC1L1 have sterol domains and have been mainly thought to transport the substance involving the sterol structure.Cholesterol is pre...

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“…The intestinal cellular uptake of vitamin E from mixed micelles follows in principle two different pathways across enterocytes, as has been shown in vitro and in vivo: (1) passive diffusion; and (2) receptor-mediated transport. Receptors facilitating α-TOH transport across the enterocyte membrane, similar to the intestinal uptake of cholesterol [54] , are the class B type 1 scavenger receptor class B type 1 (SR-B1) [55] and the Niemann-Pick C1-like protein 1 (NPC1L1), an apical membrane receptor of the small intestine [56] . The ATP-binding cassette (ABC) transporters ABCG5/ABCG8, at the luminal site, and ABCA1, at the apical site, are responsible for steroid efflux into the intestinal lumen and transport into the lymph system, respectively [57,58] .…”

Section: Intestinal Absorptionmentioning

confidence: 99%

Complexity of vitamin E metabolism

Schmölz¹,

Birringer²,

Lorkowski³

et al. 2016

WJBC

183

138

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Bioavailability of vitamin E is influenced by several factors, most are highlighted in this review. While gender, age and genetic constitution influence vitamin E bioavailability but cannot be modified, life-style and intake of vitamin E can be. Numerous factors must be taken into account however, i.e. , when vitamin E is orally administrated, the food matrix may contain competing nutrients. The complex metabolic processes comprise intestinal absorption, vascular transport, hepatic sorting by intracellular binding proteins, such as the significant α-tocopherol-transfer protein, and hepatic metabolism. The coordinated changes involved in the hepatic metabolism of vitamin E provide an effective physiological pathway to protect tissues against the excessive accumulation of, in particular, non-α-tocopherol forms. Metabolism of vitamin E begins with one cycle of CYP4F2/CYP3A4-dependent ω-hydroxylation followed by five cycles of subsequent β-oxidation, and forms the water-soluble end-product carboxyethylhydroxychroman. All known hepatic metabolites can be conjugated and are excreted, depending on the length of their sidechain, either via urine or feces. The physiological handling of vitamin E underlies kinetics which vary between the different vitamin E forms. Here, saturation of the side-chain and also substitution of the chromanol ring system are important. Most of the metabolic reactions and processes that are involved with vitamin E are also shared by other fat soluble vitamins. Influencing interactions with other nutrients such as vitamin K or pharmaceuticals are also covered by this review. All these processes modulate the formation of vitamin E metabolites and their concentrations in tissues and body fluids. Differences in metabolism might be responsible for the discrepancies that have been observed in studies performed in vivo and in vitro using vitamin E as a REVIEW

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Niemann-Pick C1-Like 1 Mediates α-Tocopherol Transport

Cited by 134 publications

References 27 publications

Vitamine E et physiologie du tissu adipeux

Vitamine E et physiologie du tissu adipeux

An Approach to Improve Intestinal Absorption of Poorly Absorbed Water-Insoluble Components <i>via</i> Niemann–Pick C1-Like 1

Complexity of vitamin E metabolism

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