Impact of vitamin A transport and storage on intestinal retinoid homeostasis and functions
| Autor: | Judith Storch, Costantino Vetriani, Nina Isoherranen, Guo Zhong, Yana Bromberg, Harini Sampath, Loredana Quadro, Aaron C. Ericsson, Paul A. S. Breslin, Maryam Honarbakhsh, Laurie B. Joseph, Charlene B. Van Buiten, Kiana Malta, Michael L. Chikindas, Atreju I. Lackey, Chengsheng Zhu |
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| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
RBP or RBP4 retinol-binding protein VA-suf vitamin A sufficient Vitamin A transport PERMANOVA permutational multivariate analysis of variance gut microbiome 030204 cardiovascular system & hematology Biochemistry vitamin A chemistry.chemical_compound 0302 clinical medicine Endocrinology lecithin:retinol acyltransferase retinoic acid RA retinoic acid Retinoid NIRF near-infrared fluorescence Tissue homeostasis VA vitamin A Retinol Muc mucin VAD vitamin A deficiency PAS Periodic Acid-Schiff SCFA short-chain fatty acid VA-def vitamin A deficient Research Article medicine.medical_specialty medicine.drug_class QD415-436 03 medical and health sciences ROS reactive oxygen species Internal medicine OTU operational taxonomic unit medicine Rbp−/− retinol-binding protein–deficient mice PCA principal component analysis colon LRAT lecithin:retinol acyltransferase RE retinyl esters Cell Biology retinol-binding protein medicine.disease IL interleukin Vitamin A deficiency Retinol binding protein 030104 developmental biology chemistry RegIII regenerating islet-derived protein 3 Lrat−/− lecithin:retinol acyltransferase–deficient mice vitamin A deficiency Lecithin retinol acyltransferase ROH retinol Dysbiosis |
| Zdroj: | Journal of Lipid Research Journal of Lipid Research, Vol 62, Iss, Pp 100046-(2021) |
| ISSN: | 0022-2275 |
| DOI: | 10.1016/j.jlr.2021.100046 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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