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,3
* Department of International Health, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD 21205 and
Phytonutrients Laboratory and
** Nutrient Requirements and Functions Laboratory, U.S. Department of Agriculture-Agricultural Research Service, Beltsville, MD 20705
3To whom correspondence should be addressed. E-mail: duringa{at}ba.ars.usda.gov.
Data suggest that intestinal carotenoid absorption is a facilitated process. The present study was conducted to determine whether carotenoids and cholesterol share common pathways (transporters) for their intestinal absorption. Differentiated Caco-2 cells on membranes were incubated (16 h) with a carotenoid (1 µmol/L) with or without ezetimibe (EZ; Zetia®, an inhibitor of cholesterol transport), and with or without antibodies against the receptors, cluster determinant 36 (CD36) and scavenger receptor class B, type I (SR-BI). Carotenoid transport in Caco-2 cells (cellular uptake + secretion) was decreased by EZ (10 mg/L) as follows: ß-carotene 
-carotene (50% inhibition) >> ß-cryptoxanthin lycopene (20%) >> lutein:zeaxanthin (1:1) (7%). EZ reduced cholesterol transport by 31%, but not retinol transport. ß-Carotene transport was also inhibited by anti-SR-BI, but not by anti-CD36. The inhibitory effects of EZ and anti-SR-BI on ß-carotene transport were additive, indicating that they may have different targets. Finally, differentiated Caco-2 cells treated with EZ showed a significant decrease in mRNA expression for the surface receptors SR-BI, Niemann-Pick type C1 Like 1 protein (NPC1L1), and ATP-binding cassette transporter, subfamily A (ABCA1) and for the nuclear receptors retinoid acid receptor (RAR)
, sterol-regulatory element binding proteins (SREBP)-1 and -2, and liver X receptor (LXR)ß as assessed by real-time PCR analysis. The data indicate that 1) EZ is an inhibitor of carotenoid transport, an effect that decreases with increasing polarity of the carotenoid molecule, 2) SR-BI is involved in carotenoid transport, and 3) EZ may act, not only by interacting physically with cholesterol transporters as previously suggested, but also by downregulating expression of these proteins. The cellular uptake and efflux of carotenoids, like that of cholesterol, likely involve more than one transporter.
KEY WORDS: • carotenoids • intestinal absorption • ezetimibe • facilitated transport • Caco-2 cells
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