Polyunsaturated fatty acids (PUFA) are a source of bioactive lipids regulating inflammation and its resolution. 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. 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. 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.

中文翻译：

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年龄对泪腺生物活性脂质的影响


多不饱和脂肪酸 (PUFA) 是调节炎症及其消退的生物活性脂质的来源。使用靶向脂质组学分析比较了年轻和老年 C57BL/6 J 小鼠泪腺 (LG) 的 PUFA 代谢变化，以及参与这些脂质代谢的酶的基因表达。与年轻对照组相比，老年 LG 中的 PUFA 及其代谢物总体减少，所有分析物平均减少 25% 至 66%。老年LG中的ꞷ-6花生四烯酸（AA）代谢物均减少，其中前列腺素E2（PGE2）和脂氧素A4（LXA4）的变化具有统计学意义。老年 LG 中其他几种 5-脂氧合酶 (5-LOX) 介导的代谢物显着减少，包括 D 系列分解素（例如 RvD4、RvD5 和 RvD6）。随着 RvD 的增加，老年 LG 中的几种 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 MaR 1 代谢物 (22-COOH-MaR1) 显着减少。同样，在老年 LG 中，ꞷ-3 二十碳五烯酸 (EPA) 及其代谢物显着减少，其中减少最显着的是 18-HEPE。使用特定代谢转化的代谢物比率（产物：前体）作为替代酶测量，在老年 LG 中发现 12-LOX 活性降低。在这项研究中，与年轻对照相比，老年女性 C57BL/6 J 的 LG 中发现 PUFA 及其代谢物整体减少。在老年小鼠中，除 ꞷ-3 二十二碳五烯酸 (DPA) 及其特殊的促分解介质 (SPM) 代谢物外，所有检测到的脂质分析物均观察到一致的减少，表明 LG 炎症的风险增加。