Mechanisms of Cell Uptake and Transport of Xanthophylls in the Caco-2 Cell Model.

BACKGROUND/OBJECTIVES:Zeaxanthin and lutein, which are essential dietary xanthophylls existing abundantly in free and esterified forms, require efficient intestinal absorption due to their insufficient synthesis in humans. However, limited knowledge on intestinal uptake and transport of xanthophyll esters is available. METHODS:This study investigated the cellular uptake and transport mechanism of free and esterified xanthophylls using human Caco-2 cell monolayer, with lutein, zeaxanthin and their dipalmitates as representatives. RESULTS:The results showed that free xanthophylls were uptaken without cellular re-esterification. Esterified xanthophylls were predominantly uptaken in free forms, as evidenced by Caco-2 cells incubated with zeaxanthin and lutein dipalmitates containing 80.8% and 89.4% of zeaxanthin and lutein, along with minor amounts of monoesters and diesters, respectively. Subsequent basolateral detection of both free xanthophylls and monoesters also confirmed intact ester uptake. Additionally, time- and concentration-dependent uptake patterns were observed, with all xanthophylls showing moderate permeability. Mechanistically, SR-BI and NPC1L1 were involved in the uptake of both free and esterified xanthophylls. At the expression level, free and esterified xanthophylls differentially affected ABCG5, with significant upregulation observed only in response to free xanthophylls. Tight junction integrity remained unaffected, excluding paracellular transport. Uptake of free and esterified xanthophyll micelles also involved clathrin- and caveolae-dependent endocytosis, whereas macropinocytosis was excluded. CONCLUSIONS:These findings provide insight into the uptake behavior of free and esterified xanthophylls and the transporter- and endocytosis-related processes involved.