April 2014
Volume 55, Issue 13
Free
ARVO Annual Meeting Abstract  |   April 2014
Role of plasma HDL remodeling and intestinal ABCA1 activity in the uptake of dietary lutein and zeaxanthin
Author Affiliations & Notes
  • Eric J Niesor
    F. Hoffmann-La Roche, Basel, Switzerland
  • Evelyne Chaput
    F. Hoffmann-La Roche, Basel, Switzerland
  • Footnotes
    Commercial Relationships Eric Niesor, F. Hoffmann-La Roche (E); Evelyne Chaput, F. Hoffmann-La Roche (E)
  • Footnotes
    Support None
Investigative Ophthalmology & Visual Science April 2014, Vol.55, 3479. doi:
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      Eric J Niesor, Evelyne Chaput; Role of plasma HDL remodeling and intestinal ABCA1 activity in the uptake of dietary lutein and zeaxanthin. Invest. Ophthalmol. Vis. Sci. 2014;55(13):3479.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose: The mechanism of intestinal uptake and delivery to peripheral tissues of lutein (L) and zeaxanthin (Z), two antioxidants of dietary origin, is poorly understood. The intestinal absorption of these carotenoids is thought to involve high-density lipoproteins (HDL) and the ATP-binding cassette transporter A1 (ABCA1). We examined the effect of compounds known to modify HDL metabolism on intestinal uptake of L and Z.

Methods: We first developed an animal model to study the intestinal uptake process by feeding hamsters increasing concentrations of a dietary supplement of L and Z given as 0.01 to 0.3% Floraglo® (n=10 per group). The selected 0.1% Floraglo®-supplemented diet was fed to animals treated for 14 days with/without the cholesteryl-ester transfer protein (CETP) modulator dalcetrapib, or inhibitor anacetrapib, as well as the ABCA1- inducer liver X receptor (LXR) agonist TO901317 as a 0.320%, 0.024% and 0.008% (w:w) food admixture, respectively (n=10 per group). Plasma and liver levels of L and Z were determined by high-performance liquid chromatography mass spectrometry.

Results: Supplementation of the diet with Floraglo® resulted in a dose-dependent elevation of plasma L and Z levels. L and Z concentrations in the liver were also dramatically raised, and tightly correlated with plasma levels. Treatment with dalcetrapib, which is known to increase HDL remodeling and pre-β-HDL formation, doubled plasma and liver L (+95% p<0.001 and +90%; p<0.001, respectively) and Z (+101%; p<0.001 and +109%; p< 0.001, respectively), without significantly increasing plasma HDL-cholesterol (HDL-C). Anacetrapib, which decreases CETP activity without allowing HDL remodelling, did not modify plasma and liver L and decreased plasma and liver Z (-32 and -31%; p<0.05, respectively) despite a 54% (p<0.001) increase in plasma HDL-C. Treatment with the LXR agonist TO901317 produced a marked increase in plasma L (+270%; p<0.001) and Z (+283%; p<0.001). However, liver concentrations of L and Z were marginally or not altered (+33%; p<0.0001, and +29%; ns, respectively) and occurred in the presence of expected hyperlipidemia.

Conclusions: Results suggest that HDL remodelling, allowing the formation of pre-β-HDL, and activity of intestinal ABCA1, are functionally important in the uptake of dietary L and Z. Plasma HDL-C levels do not reflect this process, especially following complete CETP inhibition.

Keywords: 412 age-related macular degeneration • 444 carotenoids/carotenoid binding proteins • 587 macular pigment  
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