PDF(Pubmed)
Abstract：
Exocrine meibomian glands (MGs) play a central role in the ocular physiology and biochemistry by producing in situ and, mostly, de novo a secretion (meibum), which is composed of a complex mixture of homologous lipids of various classes, in a metabolic pathway termed meibogenesis. Recent in vivo experiments with a number of mouse models demonstrated that inactivation of any of the major genes of meibogenesis led to alterations in the lipid composition of meibum and severe ocular and MG abnormalities that replicated various human ocular pathologies. However, the role of dietary lipids in meibogenesis, and in the onset and/or alleviation of these diseases, remains controversial. To uncover the role of dietary lipids, the metabolic transformations of a dietary lipid tracer-stable isotope-labeled glyceryl tri(oleate-1,2,3,7,8-13C5) (13C15-TO)-were investigated using liquid chromatography-high-resolution mass spectrometry. We demonstrated that major metabolic transformations of the tracer occurred in the stomach and small intestines where 13C15-TO underwent immediate and extensive transesterification into 13C5- and 13C10-substituted triacylglycerols of various lengths, giving a mixture of 13C-labeled compounds that remain virtually unchanged in the mouse plasma, liver, and white adipose tissue but were almost undetectable in the feces. Importantly, the tracer and its metabolites were virtually undetectable in MGs, even after 4 weeks of daily supplementation. Notably, unbiased principal component analysis of the data revealed no measurable changes in the overall chemical composition of meibum after the treatment, which implies no direct effect of dietary triacylglycerols on meibogenesis, and left their systemic effects as the most likely mechanism.
摘要：
外分泌睑板腺(MGs)在眼部生理学和生物化学中起着核心作用,大多数情况下，从头，分泌物（meibum），它由不同种类的同源脂质的复杂混合物组成，在被称为细胞生成的代谢途径中。最近用许多小鼠模型进行的体内实验表明，任何主要的骨髓生成基因的失活都会导致睑脂的脂质组成发生变化，并导致严重的眼部和MG异常，从而复制了各种人类眼部病理。然而,膳食脂质在胚胎发育中的作用，在这些疾病的发作和/或缓解中，仍然有争议。为了揭示膳食脂质的作用，使用LC高分辨率TOF-MS/MS研究了膳食脂质示踪剂-稳定的同位素标记的甘油基三（油酸-1,2,3,7,8-13C5）（13C15-TO）的代谢转化。我们证明了示踪剂的主要代谢转化发生在胃和小肠中，其中13C15-TO立即广泛地酯交换为各种长度的13C5和13C10取代的三酰基甘油，提供13C标记化合物的混合物，这些化合物在小鼠血浆中几乎保持不变，肝脏,和白色脂肪组织，但在粪便中几乎检测不到.重要的是,示踪剂及其代谢物在MGs中几乎检测不到，即使每天补充4周后。值得注意的是,数据的无偏主成分分析显示，治疗后的meibum整体化学成分没有可测量的变化，这意味着膳食三酰甘油对骨髓生成没有直接影响，并将其全身效应作为最可能的机制。
