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3 Institut National de la Recherche Agronomique, UMR1260 Nutriments Lipidiques et Prévention des Maladies Métaboliques, F–13385 Marseille, France; 4 Institut National de la Santé et de la Recherche Médicale, U476, F–13385 Marseille, France; 5 Université Aix-Marseille 1, Univ Aix-Marseille 2, Faculté de Médecine, Institut de Physiopathologie Humaine de Marseille-Institut Fédératif de Recherche 125, F–13385 Marseille, France; 6 INSERM, U563 Centre de Physiopathologie de Toulouse Purpan, Département Lipoprotéines et Médiateurs Lipidiques, IFR30 and Université Paul Sabatier, F–31024 Toulouse, France; and 7 Friedrich Schiller University Jena, Institute of Nutrition, 07743 Jena, Germany
* To whom correspondence should be addressed. E-mail: patrick.borel{at}univmed.fr.
Cholesterol membrane transporters [scavenger receptor class B type I (SR-BI) and (cluster determinant 36) are involved in intestinal uptake of lutein and β-carotene, 2 of the 3 main carotenoids of the human diet. The aim of this work was therefore to determine whether SR-BI and NPC1L1 (Niemann-Pick C1-like 1), another cholesterol transporter, are implicated in absorption of lycopene, the 3rd main carotenoid of the human diet. Anti-human SR-BI antibody and block lipid transport 1 (BLT1) (a chemical inhibitor of lipid transport by SR-BI) impaired up to 60% (all-E) and (5Z)-lycopene uptake (P < 0.05) by Caco-2 cell monolayers, which were used as a model of human intestinal epithelium. The involvement of SR-BI in lycopene absorption in vivo was then verified by comparing plasma lycopene concentrations in wild-type and SR-BI transgenic mice that were fed a diet enriched with 0.25 g/kg (all-E)-lycopene for 1 mo. Plasma lycopene concentrations were
10-fold higher (P < 0.001) in mice overexpressing SR-BI in the intestine than in wild-type mice, confirming the involvement of SR-BI in lycopene absorption. Further experiments showed that (all-E)-lycopene did not affect SR-BI mRNA levels in Caco-2 cells or mouse intestine. In contrast to SR-BI, neither anti-human NPC1L1 antibody nor ezetimibe, used as inhibitors of lycopene uptake via NPC1L1, significantly impaired (all-E) or (5Z)-lycopene uptake by Caco-2 monolayers. Thus, the present data show that lycopene absorption is, at least in part, mediated by SR-BI but not by NPC1L1.
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