Niemann‐Pick C1‐like 1 Promotes Intestinal Absorption of Siphonaxanthin

Abstract

Siphonaxanthin is a carotenoid found in certain green algae, and its promising beneficial properties, such as its anti‐obesity effect, have recently been demonstrated. However, there is little information about the molecular mechanisms underlying intestinal absorption of siphonaxanthin. In this study, we aimed to elucidate how siphonaxanthin is transported across the intestinal epithelium using differentiated Caco‐2 cells (dCaco‐2 cells), recombinant proteins, and an animal model. Siphonaxanthin was taken up by dCaco‐2 cells, a model of intestinal epithelial cells, and its uptake linearly increased up to at least 6 h. Pharmacological inhibition of Nieman‐Pick C1‐like 1 (NPC1L1), but not that of scavenger receptor class B type 1 (SR‐B1), significantly suppressed siphonaxanthin uptake by dCaco‐2 cells. Results from an in vitro binding assay suggested that the N‐terminal domain of NPC1L1, which is an extracellular domain of NPC1L1, binds with siphonaxanthin. Moreover, pretreatment with ezetimibe, an inhibitor of NPC1L1, significantly decreased the plasma level of siphonaxanthin following oral administration in mice. Considered together, we concluded that NPC1L1 promotes siphonaxanthin transport across the intestinal epithelium.

Multivariate Analysis Reveals That Unsubstituted β-Ring and C8-Keto Structures Are Important Factors for Anti-Inflammatory Activity of Carotenoids

“…For the other carotenoids (echinenone, alloxanthin, siphonaxanthin, and fucoxanthin), there is no evidence that the plasma concentration can reach 1.0 µM. However, using mice and differentiated Caco-2 cells, a well-investigated model of human intestinal epithelium, we previously showed that siphonaxanthin can be absorbed from the intestine to the same extent as β-carotene and lutein [19]. Comparative studies on the intestinal absorption of carotenoids would also be important for further understanding of the anti-inflammatory activities of carotenoids.…”

“…Total lipids were extracted from the cells as described previously [19] and dissolved in 0.25 mL of methanol. After dilution with 0.75 mL of acetonitrile, 5 µL of each sample was analyzed using a Prominence HPLC system (Shimadzu, Kyoto, Japan) coupled to a QTRAP 5500 mass spectrometer (AB Sciex, Framingham, MA, USA).…”

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

“…There are no reports on the detailed transport route of emulsified ubiquinone. On the other hand, it was reported that other emulsified fat-soluble micronutrients such as vitamin K, α-tocopherol and siphonaxanthin are transported by NPC1L1 [22,23,27]. Therefore, it is possible that CoQ10 is also transported by NPC1L1.…”

Intestinal Absorption and Anti-Inflammatory Effects of Siphonein, a Siphonaxanthin Fatty Acid Ester from Green Algae

“…Hydrolyzed carotenoids (i.e., free carotenoids) are taken up by intestinal epithelial cells through both passive and facilitated diffusion pathways. Pharmacological inhibition studies suggest that scavenger receptor class B type 1 (SR-B1, encoded by SCARB1) and/or Nieman-Pick C1-like 1 (NPC1L1) are involved in facilitated diffusion of several carotenoids (8)(9)(10)(11)(12)(13). In addition, some genetic variants in SCARB1 and NPC1L1 have been reported to be associated with changes in serum concentrations of lutein and zeaxanthin, both of which are major dietary carotenoids and reported to be taken up partly through SR-B1-and NPC1L1-dependent pathways (14).…”

“…1). The biological activities of siphonaxanthin have been extensively investigated (15)(16)(17)(18)(19), and we have previously shown that its intestinal absorption is facilitated by NPC1L1 (13). However, the biological activities and intestinal absorption mechanism of siphonein, a medium-chain fatty acid ester of siphonaxanthin, remain largely unknown.…”