Department of Ophthalmology, University of Texas Southwestern Medical Center, Dallas, TX, 75390-9057, USA; The Graduate School of Biomedical Sciences, University of Texas Southwestern Medical Center, Dallas, TX, 75390-9057, USA.
Department of Ophthalmology, University of Texas Southwestern Medical Center, Dallas, TX, 75390-9057, USA.
J Steroid Biochem Mol Biol. 2021 Jul;211:105894. doi: 10.1016/j.jsbmb.2021.105894. Epub 2021 Apr 2.
Exocrine Meibomian glands (MG) play a central role in the ocular surface physiology by producing meibum - a lipid secretion composed of cholesteryl esters (CE), cholesterol (Chl), triacylgycerols (TAG), waxes and other types of lipids. MG were previously shown to synthesize Meibomian lipids (ML) in situ via a complex array of reactions termed meibogenesis. However, questions remain about the role of dietary lipids in meibogenesis. To establish if dietary Chl (DC) and TAG (DT) can participate in meibogenesis, we studied mice whose diet was supplemented with trace amounts of deuterated Chl (H-Chl) and C-labeled triolein (C-TO), and the products of their biosynthetic transformations were analyzed using LC/MS. We demonstrated that H-Chl, but not C-TO, could be directly incorporated into meibum. Furthermore, H-Chl was esterified into MG-specific ultra long H-CE, which were vastly different from plasma CE and H-CE. The measured H-Chl/Chl and H-CE/CE ratios in meibum increased in a time-dependent manner reaching ∼5% and ∼1.2 %, respectively. The H-Chl/H-CE ratio was about 3.5x higher than that for endogenous unlabeled Chl and CE, indicating accumulation of H-Chl in meibum. The elongation pattern of Meibomian H-CE closely replicated that of unlabeled CE. On the other hand, C-TO was not detected in any of the ML samples as an intact lipid or its metabolized/hydrolyzed products. We conclude that DC can be directly esterified into MG-specific CE, while DT undergo extensive catabolic transformations before reaching MG. These findings demonstrate that DC can have a direct impact on MG and ocular surface lipid homeostasis and pathophysiology.
外分泌的睑板腺（MG）通过产生睑脂发挥着在眼表面生理学中的核心作用，其中睑脂是由胆固醇酯（CE）、胆固醇（Chl）、三酰基甘油（TAG）、蜡质和其他类型的脂质组成的脂质分泌物。先前已经表明，MG 通过一种复杂的称为睑板腺生成的反应来原位合成睑板腺脂质（ML）。然而，关于饮食脂质在睑板腺生成中的作用仍存在疑问。为了确定饮食中的胆固醇（DC）和三酰基甘油（DT）是否可以参与睑板腺生成，我们研究了饮食中补充痕量氘化胆固醇（H-Chl）和 C 标记的三油酸甘油酯（C-TO）的小鼠，并用 LC/MS 分析其生物合成转化产物。我们证明 H-Chl 可以直接掺入睑脂中，但 C-TO 不能。此外，H-Chl 酯化形成了 MG 特有的超长 H-CE，其与血浆 CE 和 H-CE 有很大不同。在时间依赖性方式下，H-Chl/Chl 和 H-CE/CE 的测量比值分别增加到约 5%和 1.2%。H-Chl/H-CE 比值约为内源性未标记的 Chl 和 CE 的 3.5 倍，表明 H-Chl 在睑脂中积累。睑板腺 H-CE 的伸长模式与未标记的 CE 非常相似。另一方面，在任何 ML 样品中都未检测到 C-TO 作为完整脂质或其代谢/水解产物。我们得出结论，DC 可以直接酯化形成 MG 特有的 CE，而 DT 在到达 MG 之前经历广泛的代谢转化。这些发现表明，DC 可以直接影响 MG 和眼表面脂质的动态平衡和病理生理学。
