Differential effects of dietary cholesterol and triglycerides on the lipid homeostasis in Meibomian glands.
Differential effects of dietary cholesterol and triglycerides on the lipid homeostasis in Meibomian glands.
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DOI：
10.1016/j.jsbmb.2021.105894
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发表时间：
2021-07
期刊：
影响因子：
--
通讯作者：
Yuksel S
中科院分区：
文献类型：
--
作者：
Butovich IA;Wilkerson A;Yuksel S
外分泌睑脂腺（MG）通过产生睑脂在眼表生理中发挥核心作用。睑脂是一种由胆固醇酯（CE）、胆固醇（Chl）、甘油三酯（TAG）、蜡质和其他类型的脂质组成的脂质分泌。MG先前被证明可以通过一系列称为减数生成的复杂反应原位合成Meibomian脂（ML）。然而，关于饮食中的脂质在新陈代谢中的作用仍然存在疑问。为了确定饲粮中Chl （DC）和TAG （DT）是否参与代谢发生，我们研究了饲粮中添加微量氘化Chl （2H-Chl）和13c标记三油酸（13C-TO）的小鼠，并利用LC/MS对其生物合成转化产物进行了分析。我们证明了2H-Chl，而不是13C-TO，可以直接结合到代谢中。此外，2H-Chl被酯化成mg特异性的超长2H-CE，这与血浆CE和2H-CE有很大的不同。测定的基质中2H-Chl/Chl和2H-CE/CE比值随时间的增加分别达到~5%和~1.2%。2H-Chl/2H-CE比内源性未标记Chl和CE高约3.5倍，说明代谢产物中有2H-Chl的积累。Meibomian 2H-CE的延伸模式与未标记CE的相似。另一方面，在任何ML样品中都没有检测到13C-TO作为完整的脂质或其代谢/水解产物。我们得出结论，DC可以直接酯化成MG特异性CE，而DT在到达MG之前经过广泛的分解代谢转化。这些结果表明，DC可直接影响MG和眼表面脂质稳态和病理生理。
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 (2H-Chl) and 13C-labeled triolein (13C-TO), and the products of their biosynthetic transformations were analyzed using LC/MS. We demonstrated that 2H-Chl, but not 13C-TO, could be directly incorporated into meibum. Furthermore, 2H-Chl was esterified into MG-specific ultra long 2H-CE, which were vastly different from plasma CE and 2H-CE. The measured 2H-Chl/Chl and 2H-CE/CE ratios in meibum increased in a time-dependent manner reaching ~5% and ~1.2%, respectively. The 2H-Chl/2H-CE ratio was about 3.5x higher than that for endogenous unlabeled Chl and CE, indicating accumulation of 2H-Chl in meibum. The elongation pattern of Meibomian 2H-CE closely replicated that of unlabeled CE. On the other hand, 13C-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.
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影响因子：
4.5
作者：
Chun YH;Kim HR;Han K;Park YG;Song HJ;Na KS
通讯作者：
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影响因子：
4.4
作者：
Arciniega, Juan C.;Uchiyama, Eduardo;Butovich, Igor A.
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DOI：
10.3980/j.issn.2222-3959.2013.06.13
发表时间：
2013-12-18
影响因子：
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作者：
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影响因子：
4.4
作者：
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影响因子：
4.1
作者：
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