Brandon Ebright , Zhiyuan Yu , Priyal Dave , Dante Dikeman , Sarah Hamm-Alvarez , Cintia S. de Paiva , Stan Louie
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Several other 5-lipoxygenase (5-LOX) mediated metabolites were significantly reduced in the aged LGs, including D-series resolvins (e.g., RvD4, RvD5, and RvD6). Along with the RvDs, several ꞷ-3 docosahexaenoic acid (DHA) metabolites such as 14-HDHA, neuroprotectin D1 (NPD1), Maresin 2 (MaR2), and MaR 1 metabolite (22-COOH-MaR1) were significantly reduced in aged LGs. Similarly, ꞷ-3 eicosapentaenoic acid (EPA) and its metabolites were significantly reduced in aged LGs, where the most significantly reduced was 18-HEPE. Using metabolite ratios (product:precursor) for specific metabolic conversions as surrogate enzymatic measures, reduced 12-LOX activity was identified in aged LGs.</p></div><div><h3>Conclusion</h3><p>In this study, global reduction of PUFAs and their metabolites was found in the LGs of aged female C57BL/6 J compared to young controls. 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引用次数: 0
摘要
目的：多不饱和脂肪酸（PUFA）是调节炎症及其缓解的生物活性脂质的来源：方法：使用靶向脂质组学分析方法比较了年轻和年老 C57BL/6J 小鼠泪腺（LGs）中多不饱和脂肪酸代谢的变化，以及参与这些脂质代谢的酶的基因表达：结果：与年轻对照组相比，老年 LG 中的 PUFAs 及其代谢物全面减少，所有分析物的平均减少率在 25-66% 之间。ꞷ-6花生四烯酸（AA）代谢物在老年 LG 中全部减少，其中前列腺素 E2（PGE2）和脂氧素 A4（LXA4）的变化具有统计学意义。其他几种由 5-脂氧合酶（5-LOX）介导的代谢物在老年 LG 中也明显减少，包括 D 系列 resolvins（如 RvD4、RvD5 和 RvD6）。除了 RvDs 之外，一些ꞷ-3 二十二碳六烯酸（DHA）代谢物，如 14-HDHA、神经保护素 D1（NPD1）、Maresin 2（MaR2）和 MaR1 代谢物（22-COOH-MaR1）也在老化 LG 中明显减少。同样，ꞷ-3二十碳五烯酸（EPA）及其代谢物在老年 LG 中也明显减少，其中减少最明显的是 18-HEPE。利用特定代谢转换的代谢物比率（产物：前体）作为替代酶测量指标，可以确定老化 LG 中 12-LOX 活性降低：在这项研究中，与年轻对照组相比，发现老年雌性 C57BL/6J LG 中的 PUFAs 及其代谢物全面减少。除了ꞷ-3二十二碳五烯酸（DPA）及其特殊的促溶解介质（SPM）外，所有检测到的脂质分析物在老年小鼠中都出现了一致的减少，这表明LG炎症的风险增加了。
Polyunsaturated fatty acids (PUFA) are a source of bioactive lipids regulating inflammation and its resolution.
Methods
Changes in PUFA metabolism were compared between lacrimal glands (LGs) from young and aged C57BL/6 J mice using a targeted lipidomics assay, as was the gene expression of enzymes involved in the metabolism of these lipids.
Results
Global reduction in PUFAs and their metabolites was observed in aged LGs compared to young controls, averaging between 25 and 66 % across all analytes. ꞷ-6 arachidonic acid (AA) metabolites were all reduced in aged LGs, where the changes in prostaglandin E2 (PGE2) and lipoxin A4 (LXA4) were statistically significant. Several other 5-lipoxygenase (5-LOX) mediated metabolites were significantly reduced in the aged LGs, including D-series resolvins (e.g., RvD4, RvD5, and RvD6). Along with the RvDs, several ꞷ-3 docosahexaenoic acid (DHA) metabolites such as 14-HDHA, neuroprotectin D1 (NPD1), Maresin 2 (MaR2), and MaR 1 metabolite (22-COOH-MaR1) were significantly reduced in aged LGs. Similarly, ꞷ-3 eicosapentaenoic acid (EPA) and its metabolites were significantly reduced in aged LGs, where the most significantly reduced was 18-HEPE. Using metabolite ratios (product:precursor) for specific metabolic conversions as surrogate enzymatic measures, reduced 12-LOX activity was identified in aged LGs.
Conclusion
In this study, global reduction of PUFAs and their metabolites was found in the LGs of aged female C57BL/6 J compared to young controls. A consistent reduction was observed across all detected lipid analytes except for ꞷ-3 docosapentaenoic acid (DPA) and its special pro-resolving mediator (SPM) metabolites in aged mice, suggesting an increased risk for LG inflammation.
期刊介绍：
The Ocular Surface, a quarterly, a peer-reviewed journal, is an authoritative resource that integrates and interprets major findings in diverse fields related to the ocular surface, including ophthalmology, optometry, genetics, molecular biology, pharmacology, immunology, infectious disease, and epidemiology. Its critical review articles cover the most current knowledge on medical and surgical management of ocular surface pathology, new understandings of ocular surface physiology, the meaning of recent discoveries on how the ocular surface responds to injury and disease, and updates on drug and device development. The journal also publishes select original research reports and articles describing cutting-edge techniques and technology in the field.
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