A genetic dissection of intestinal fat-soluble vitamin and carotenoid absorption

M. Airanthi, K. Widjaja-Adhi, Glenn P. Lobo, Marcin Golczak, Johannes Von Lintig

Research output: Contribution to journalArticlepeer-review

Abstract

Carotenoids are currently investigated regarding their potential to lower the risk of chronic disease and to combat vitamin A deficiency. Surprisingly, responses to dietary supplementation with these compounds are quite variable between individuals. Genome-wide studies have associated common genetic polymorphisms in the BCO1 gene with this variability. The BCO1 gene encodes an enzyme that is expressed in the intestine and converts provitamin A carotenoids to vitamin A-aldehyde. However, it is not clear how this enzyme can impact the bioavailability and metabolismof other carotenoids such as xanthophyll.We here provide evidence that BCO1 is a key component of a regulatory network that controls the absorption of carotenoids and fatsoluble vitamins. In this process, conversion of β-carotene to vitamin A by BCO1 induces via retinoid signaling the expression of the intestinal homeobox transcription factor ISX. Subsequently, ISX binds to conserved DNA-binding motifs upstream of the BCO1 and SCARB1 genes. SCARB1 encodes a membrane protein that facilitates absorption of fat-soluble vitamins and carotenoids. In keeping with its role as a transcriptional repressor, SCARB1 protein levels are significantly increased in the intestine of ISX-deficient mice. This increase results in augmented absorption and tissue accumulation of xanthophyll carotenoids and tocopherols. Our study shows that fat-soluble vitamin and carotenoid absorption is controlled by a BCO1- dependent negative feedback regulation. Thus, our findings provide a molecular framework for the controversial relationship between genetics and fat-soluble vitamin status in the human population.

Original languageEnglish (US)
Pages (from-to)3206-3219
Number of pages14
JournalHuman molecular genetics
Volume24
Issue number11
DOIs
StatePublished - Dec 15 2014
Externally publishedYes

Bibliographical note

Publisher Copyright:
© The Author 2015.

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