The Molecular Basis of Retinoid Absorption
Open accessAbstract
The intestine and other tissues are able to synthesize retinyl esters in an acyl-CoA-dependent manner involving an acyl-CoA:retinol acyltransferase (ARAT). However, the molecular identity of this ARAT has not been established. Recent studies of lecithin:retinol acyltransferase (LRAT)-deficient mice indicate that LRAT is responsible for the preponderance of retinyl ester synthesis in the body, aside from in the intestine and adipose tissue. Our present studies, employing a number of mutant mouse models, identify diacylglycerol acyltransferase 1 (DGAT1) as an important intestinal ARAT in vivo. The contribution that DGAT1 makes to intestinal retinyl ester synthesis becomes greater when a large pharmacologic dose of retinol is administered by gavage to mice. Moreover, when large retinol doses are administered another intestinal enzyme(s) with ARAT activity becomes apparent. Surprisingly, although DGAT1 is expressed in adipose tissue, DGAT1 does not catalyze retinyl ester synthesis in adipose tissue in vivo. Our data also establish that cellular retinol-binding protein, type II (CRBPII), which is expressed solely in the adult intestine, in vivo channels retinol to LRAT for retinyl ester synthesis. Contrary to what has been proposed in the literature based on in vitro studies, CRBPII does not directly prevent retinol from being acted upon by DGAT1 or other intestinal ARATs in vivo.
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The main function of CRBP2 is to transport vitamin A across the cytoplasm to the endoplasmic reticulum, where retinol becomes esterified by LRAT and DGAT1.
“The main function of CRBP2 is to transport vitamin A across the cytoplasm to the endoplasmic reticulum, where retinol becomes esterified by the action of two non-related proteins: lecithin:retinol acyltransferase (LRAT) and diacylglycerol O-acyltransferase 1 (DGAT1) [37].”
From Molecular Basis for Vitamin A Uptake and Storage in Vertebrates (2016) · cites this paper as [37]
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“The main function of CRBP2 is to transport vitamin A across the cytoplasm to the endoplasmic reticulum, where retinol becomes esterified by the action of two non‐related proteins: lecithin:retinol acyltransferase (LRAT) and diacylglycerol O‐acyltransferase 1 (DGAT1) [37].”
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- Authors
- Wongsiriroj, N., Piantedosi, R., Palczewski, K., Goldberg, I. J., Johnston, T. P., Li, E., & Blaner, W. S.
- Affiliations
- Columbia University (US)
- Case Western Reserve University (US)
- University of Missouri–Kansas City (US)
- Washington University in St. Louis (US)
- Corresponding author
- Blaner, William S.
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 2008-05
- Volume
- 283
- Issue
- 20
- Pages
- 13510-13519
- ISSN
- 0021-9258 (ISSN-L)
- PMC
- PMC2376245
- OpenAlex
- W2045463616
- Cited by
- 126
- References
- 4
- Citations by year
- 2026: 2 · 2025: 3 · 2024: 7 · 2023: 3 · 2022: 10 · 2021: 6 · 2020: 7 · 2019: 6 · 2018: 1 · 2017: 5 · 2016: 6 · 2015: 10 · 2014: 5 · 2013: 12 · 2012: 9
- FWCI
- 4.67
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Biological Chemistry (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Eye Institute (R01 EY 09339, R01EY008123, R01 EY08123, R01EY009339)
- National Institute of Diabetes and Digestive and Kidney Diseases (R01DK068437, R01DK061310, R01DK079221, P30DK052574)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Retinoids in leukemia and cellular processes
- Health Sciences › Medicine › Surgery › Cholesterol and Lipid Metabolism
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Lipid metabolism and biosynthesis
- Keywords
- DGAT1, LRAT, adipose tissue, retinol, mutant mouse models
- MeSH terms
- Adipose Tissue, Animals, Chromatography, High Pressure Liquid, Esters, Intestinal Mucosa, Phosphatidylcholine-Sterol O-Acyltransferase, Mice, Inbred C57BL, Mice, Transgenic, Models, Biological, Models, Genetic, Retinoids, Diacylglycerol O-Acyltransferase, Mice, Retinol-Binding Proteins, Cellular
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