Effect of Compounds Affecting ABCA1 Expression and CETP Activity on the HDL Pathway Involved in Intestinal Absorption of Lutein and Zeaxanthin

Abstract

The antioxidant xanthophylls lutein and zeaxanthin are absorbed from the diet in a process involving lipoprotein formation. Selective mechanisms exist for their intestinal uptake and tissue-selective distribution, but these are poorly understood. We investigated the role of high-density lipoprotein (HDL), apolipoprotein (apo) A1 and ATP-binding cassette transporter (ABC) A1 in intestinal uptake of lutein in a human polarized intestinal cell culture and a hamster model. Animals received dietary lutein and zeaxanthin and either a liver X receptor (LXR) agonist or statin, which up- or down-regulate intestinal ABCA1 expression, respectively. The role of HDL was studied following treatment with the cholesteryl ester transfer protein (CETP) modulator dalcetrapib or the CETP inhibitor anacetrapib. In vitro, intestinal ABCA1 at the basolateral surface of enterocytes transferred lutein and zeaxanthin to apoA1, not to mature HDL. In hamsters, plasma lutein and zeaxanthin levels were markedly increased with the LXR agonist and decreased with simvastatin. Dalcetrapib, but not anacetrapib, increased plasma and liver lutein and zeaxanthin levels. ABCA1 expression and apoA1 acceptor activity are important initial steps in intestinal uptake and maintenance of lutein and zeaxanthin levels by an HDL-dependent pathway. Their absorption may be improved by physiological and pharmacological interventions affecting HDL metabolism.

Determinants of HDL Cholesterol Efflux Capacity after Virgin Olive Oil Ingestion: Interrelationships with Fluidity of HDL Monolayer

“…The ABCA‐1/ApoA‐I complex absorbs antioxidants ( i.e lutein, zeaxanthin, etc.) which are LDL‐protecting molecules, thus contributing to the formation of nascent HDL . ABCA1/ApoA‐I activity is fundamental for the formation of the nascent HDL (pre‐β1 fractions), which are also efficient acceptors of cell cholesterol via ABCG1 .…”

“…which are LDL-protecting molecules, thus contributing to the formation of nascent HDL. [34] ABCA1/ApoA-I activity is fundamental for the formation of the nascent HDL (pre-β1 fractions), which are also efficient acceptors of cell cholesterol via ABCG1. [4] In agreement with our past findings, HDL oxidation decreases HDL fluidity and concomitantly CEC.…”

Statin-Induced Decrease in ATP-Binding Cassette Transporter A1 Expression via microRNA33 Induction may Counteract Cholesterol Efflux to High-Density Lipoprotein

“…It should be noted that these experiments were performed in the absence of concomitant statin treatment. Recently, we reported [27] that dalcetrapib treatment of hamsters increased the intestinal absorption of the antioxidants lutein and zeaxanthin via an HDL pathway, which is ABCA1 and ApoA1 dependent. Simvastatin treatment decreased the expression of intestinal ABCA1, decreased lutein and zeaxanthin concentrations in plasma and liver, and abrogated the effect of dalcetrapib on lutein and zeaxanthin absorption.…”

Potential Signal Transduction Regulation by HDL of the β2-Adrenergic Receptor Pathway. Implications in Selected Pathological Situations

“…We recently demonstrated that dalcetrapib (but not anacetrapib) treatment increased in vivo the intestinal uptake of two antioxidants of dietary origin-lutein and zeaxanthin (87). This process, which is like cholesterol and phospholipid efflux-an ABCA1/ApoA1 driven process-support the hypothesis that the HDL raised by dalcetrapib is functional.…”