TY - JOUR
T1 - Impact of Vitamin A transport and storage on intestinal retinoid homeostasis and functions
AU - Honarbakhsh, Maryam
AU - Ericsson, Aaron
AU - Zhong, Guo
AU - Isoherranen, Nina
AU - Zhu, Chengsheng
AU - Bromberg, Yana
AU - van Buiten, Charlene
AU - Malta, Kiana
AU - Joseph, Laurie
AU - Sampath, Harini
AU - Lackey, Atreju I.
AU - Storch, Judith
AU - Vetriani, Costantino
AU - Chikindas, Michael L.
AU - Breslin, Paul
AU - Quadro, Loredana
N1 - Funding Information: This work was partially supported by the US National Institutes of Health (NIH) R01HD083331 and R01HD094778 (to L. Q.), K01OD019924 (to A. E.), R01GM111772 (to N. I.), R01AR055073 (to L. J.), and R01DK38389 (to J. S.). This work was also partially supported by the USDA National Institute of Food and Agriculture, Hatch project, accession number 1018402 (to L. Q.), Charles and Joanna Bush Biomedical Research Program (BBRP) at Rutgers University number 659217 (to P.B.), and by the Ministry of Science and Higher Education of the Russian Federation, Project Number 075-15-2019-1880 (to M.C.).The content of this manuscript is solely the responsibility of the authors and does not necessarily represent the official views of the NIH. Publisher Copyright: © 2021 THE AUTHORS. Published by Elsevier Inc on behalf of American Society for Biochemistry and Molecular Biology. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
PY - 2021
Y1 - 2021
N2 - Lecithin:retinol acyltransferase and retinol-binding protein enable vitamin A (VA) storage and transport, respectively, maintaining tissue homeostasis of retinoids (VA derivatives). The precarious VA status of the lecithin:retinol acyltransferase-deficient (Lrat¡/¡) retinol-binding protein-deficient (Rbp−/−) mice rapidly deteriorates upon dietary VA restriction, leading to signs of severe vitamin A deficiency (VAD). As retinoids impact gut morphology and functions, VAD is often linked to intestinal pathological conditions and microbial dysbiosis. Thus, we investigated the contribution of VA storage and transport to intestinal retinoid homeostasis and functionalities. We showed the occurrence of intestinal VAD in Lrat−/−Rbp−/− mice, demonstrating the critical role of both pathways in preserving gut retinoid homeostasis. Moreover, in the mutant colon, VAD resulted in a compromised intestinal barrier as manifested by reduced mucins and antimicrobial defense, leaky gut, increased inflammation and oxidative stress, and altered mucosal immunocytokine profiles. These perturbations were accompanied by fecal dysbiosis, revealing that the VA status (sufficient vs. deficient), rather than the amount of dietary VA per se, is likely a major initial discriminant of the intestinal microbiome. Our data also pointed to a specific fecal taxonomic profile and distinct microbial functionalities associated with VAD. Overall, our findings revealed the suitability of the Lrat−/−Rbp−/− mice as a model to study intestinal dysfunctions and dysbiosis promoted by changes in tissue retinoid homeostasis induced by the host VA status and/or intake.
AB - Lecithin:retinol acyltransferase and retinol-binding protein enable vitamin A (VA) storage and transport, respectively, maintaining tissue homeostasis of retinoids (VA derivatives). The precarious VA status of the lecithin:retinol acyltransferase-deficient (Lrat¡/¡) retinol-binding protein-deficient (Rbp−/−) mice rapidly deteriorates upon dietary VA restriction, leading to signs of severe vitamin A deficiency (VAD). As retinoids impact gut morphology and functions, VAD is often linked to intestinal pathological conditions and microbial dysbiosis. Thus, we investigated the contribution of VA storage and transport to intestinal retinoid homeostasis and functionalities. We showed the occurrence of intestinal VAD in Lrat−/−Rbp−/− mice, demonstrating the critical role of both pathways in preserving gut retinoid homeostasis. Moreover, in the mutant colon, VAD resulted in a compromised intestinal barrier as manifested by reduced mucins and antimicrobial defense, leaky gut, increased inflammation and oxidative stress, and altered mucosal immunocytokine profiles. These perturbations were accompanied by fecal dysbiosis, revealing that the VA status (sufficient vs. deficient), rather than the amount of dietary VA per se, is likely a major initial discriminant of the intestinal microbiome. Our data also pointed to a specific fecal taxonomic profile and distinct microbial functionalities associated with VAD. Overall, our findings revealed the suitability of the Lrat−/−Rbp−/− mice as a model to study intestinal dysfunctions and dysbiosis promoted by changes in tissue retinoid homeostasis induced by the host VA status and/or intake.
KW - Colon
KW - Gut microbiome
KW - Lecithin:retinol acyltransferase
KW - Retinoic acid
KW - Retinol-binding protein
KW - Vitamin A
KW - Vitamin A deficiency
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U2 - https://doi.org/10.1016/J.JLR.2021.100046
DO - https://doi.org/10.1016/J.JLR.2021.100046
M3 - Article
C2 - 33587919
SN - 0022-2275
VL - 62
JO - Journal of lipid research
JF - Journal of lipid research
M1 - 100046
ER -