A genetic dissection of intestinal fat-soluble vitamin and carotenoid absorption
Open accessAbstract
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 metabolism of 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 fat-soluble 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.
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Efficiency of carotenoid absorption is controlled by a negative feedback in which ISX suppresses intestinal expression of SCARB1 and BCO1 via retinoic acid signaling directly linked with vitamin A demand.
“Thus, efficiency of carotenoids absorption is controlled by a negative feedback, in which ISX suppresses the intestinal expression of SCARB1 and the vitamin A forming enzyme BCO1 via retinoic acid signaling directly linked with the vitamin A demand of the organism [33].”
From Molecular Basis for Vitamin A Uptake and Storage in Vertebrates (2016) · cites this paper as [33]
The Introduction and Discussion (pages unavailable in our copy) describe retinoic-acid induction of ISX, suppression of intestinal BCO1 and SCARB1, and negative-feedback control of carotenoid absorption. The paper does not establish that this signaling is directly linked to the organism’s vitamin A demand; that final qualification goes beyond the evidence shown. (LLM, conf=0.82)
Experimental — accuracy not yet measuredSCARB1 can serve as a transporter for vitamins, including tocopherols, and carotenoids such as β-carotene and xanthophylls.
“Additionally, SCARB1 can also serve as a transporter for vitamins, including tocopherols, and carotenoids such as β-carotene and xanthophylls [10,11].”
From Vitamin A Transporters in Visual Function: A Mini Review on Membrane Receptors for Dietary Vitamin A Uptake, Storage, and Transport to the Eye (2021) · cites this paper as [11]
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- Authors
- Widjaja-Adhi, M. A. K., Lobo, G. P., Golczak, M., & Von Lintig, J.
- Affiliations
- Case Western Reserve University (US)
- Venue
- Human Molecular Genetics
- Publisher
- Oxford University Press (OUP)
- Published
- 2015-02-20
- Volume
- 24
- Issue
- 11
- Pages
- 3206-3219
- ISSN
- 0964-6906 (ISSN-L)
- 1460-2083
- PMC
- PMC4424956
- OpenAlex
- W2146424120
- Semantic Scholar
- b64169928fb22784a352c60fb60f8eef036f2241
- Cited by
- 126
- References
- 61
- Citations by year
- 2026: 10 · 2025: 12 · 2024: 11 · 2023: 8 · 2022: 20 · 2021: 14 · 2020: 13 · 2019: 11 · 2018: 10 · 2017: 7 · 2016: 8 · 2015: 2
- FWCI
- 6.09
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Human Molecular Genetics (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Case Western Reserve University
- National Eye Institute (R01EY019641, R01EY020551, R01EY023948)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Nutrition, Genetics, and Disease
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Retinoids in leukemia and cellular processes
- Health Sciences › Medicine › Biochemistry › Antioxidant Activity and Oxidative Stress
- Keywords
- carotenoid absorption, fat-soluble vitamin absorption, BCO1, Iraq Stock Exchange, scavenger receptor class B type I, retinoid signaling, xanthophyll carotenoids, tocopherols, negative feedback regulation, genetic polymorphism, vitamin A deficiency, bioavailability
- MeSH terms
- Animals, Base Sequence, Binding Sites, Eye, Female, Intestinal Absorption, Male, Mice, Inbred C57BL, Promoter Regions, Genetic, Solubility, Transcription Factors, Transcriptional Activation, Gene Expression, Mice, Knockout, Xanthophylls, Scavenger Receptors, Class B, Mice, 129 Strain, Zeaxanthins
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