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Dynamics of vitamin A uptake, storage, and utilization in vocal fold mucosa.
Molecular Metabolism ( IF 8.1 ) Pub Date : 2020-05-28 , DOI: 10.1016/j.molmet.2020.101025
Kohei Nishimoto 1 , Yutaka Toya 1 , Christopher R Davis 2 , Sherry A Tanumihardjo 2 , Nathan V Welham 1
Affiliation  

Objective

Extrahepatic vitamin A is housed within organ-specific stellate cells that support local tissue function. These cells have been reported in the vocal fold mucosa (VFM) of the larynx; however, it is unknown how vitamin A reaches and is disseminated among VFM target cells, how VFM storage and utilization vary as a function of total body stores, and how these parameters change in the context of pathology. Therefore, in this study, we investigated fundamental VFM vitamin A uptake and metabolism.

Methods

Using cadaveric tissue and serum from human donors representing the full continuum of clinical vitamin A status, we established a concentration range and analyzed the impact of biologic and clinical covariates on VFM vitamin A. We additionally conducted immunodetection of vitamin A-associated markers and pharmacokinetic profiling of orally dosed α-retinyl ester (a chylomicron tracer) in rats.

Results

Serum vitamin A was a significant predictor of human VFM concentrations, suggesting that VFM stores may be rapidly metabolized in situ and replenished from the circulatory pool. On a vitamin A-sufficient background, dosed α-vitamin A was detected in rat VFM in both ester and alcohol forms, showing that, in addition to plasma retinol and local stellate cell stores, VFM can access and process postprandial retinyl esters from circulating chylomicra. Both α forms were rapidly depleted, confirming the high metabolic demand for vitamin A within VFM.

Conclusion

This thorough physiological analysis validates VFM as an extrahepatic vitamin A repository and characterizes its unique uptake, storage, and utilization phenotype.



中文翻译:

声带粘膜中维生素A吸收,存储和利用的动力学。

目的

肝外维生素A容纳在支持局部组织功能的器官特异性星状细胞中。据报道,这些细胞存在于喉部的声带粘膜(VFM)中。但是,尚不知道维生素A如何到达VFM目标细胞并在VFM目标细胞中传播,VFM的存储和利用如何随身体存储而变化,以及这些参数在病理情况下如何变化。因此,在这项研究中,我们研究了基本的VFM维生素A摄取和代谢。

方法

我们使用人体供体的尸体组织和血清代表临床维生素A状态的完整连续体,我们确定了浓度范围,并分析了生物学和临床协变量对VFM维生素A的影响。我们还进行了维生素A相关标志物的免疫检测和药代动力学分析在大鼠中口服α-视黄酯(乳糜微粒示踪剂)的剂量。

结果

血清维生素A是人类VFM浓度的重要预测指标,表明VFM存储库可能在原位快速代谢并从循环池中补充。在维生素A充足的背景下,在大鼠VFM中检测到以酯和醇形式存在的α-维生素A剂量,这表明,除了血浆视黄醇和局部星状细胞存储外,VFM还可以从循环乳糜中获取和加工餐后视黄酯。 。两种α形式都被迅速耗尽,证实了VFM中对维生素A的高代谢需求。

结论

这项详尽的生理分析证实了VFM是肝外维生素A储存库,并表征了其独特的摄取,储存和利用表型。

更新日期:2020-05-28
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