Division of Otolaryngology, Department of Surgery, University of Wisconsin School of Medicine and Public Health, Madison, WI, 53792, USA.
Department of Nutritional Sciences, University of Wisconsin-Madison, Madison, WI, 53706, USA.
Mol Metab. 2020 Oct;40:101025. doi: 10.1016/j.molmet.2020.101025. Epub 2020 May 28.
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.
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.
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.
This thorough physiological analysis validates VFM as an extrahepatic vitamin A repository and characterizes its unique uptake, storage, and utilization phenotype.
肝外维生素 A 储存在特定于器官的星状细胞内,这些细胞支持局部组织功能。这些细胞已在喉的声带黏膜(VFM)中被报道;然而,目前尚不清楚维生素 A 如何到达并在 VFM 靶细胞中扩散,VFM 的储存和利用如何随全身储存量而变化,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。
使用来自代表临床维生素 A 状态全貌的人体供体的尸体组织和血清,我们建立了浓度范围,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经口给予 α-视黄酯(乳糜微粒示踪剂)在大鼠中的药代动力学分析。
血清维生素 A 是人类 VFM 浓度的重要预测因素,表明 VFM 储存可能在局部迅速代谢,并从循环池中补充。在维生素 A 充足的背景下,大鼠 VFM 中检测到经口给予的 α-维生素 A 以酯和醇的形式存在,表明除了血浆视黄醇和局部星状细胞储存外,VFM 还可以从循环乳糜微粒中摄取和处理餐后视黄酯。两种形式的 α 都迅速耗尽,证实了 VFM 对维生素 A 的高代谢需求。
这项全面的生理学分析验证了 VFM 作为肝外维生素 A 储存库的作用,并描述了其独特的摄取、储存和利用表型。