Manson Anne, Winter Tanja, Aukema Harold M
Food and Human Nutritional Sciences, University of Manitoba, 66 Chancellors Cir, R3T 2N2 Winnipeg, MB, Canada; Canadian Centre for Agri-Food Research in Health and Medicine (CCARM), St. Boniface Hospital Albrechtsen Research Centre, 351 Tache Avenue - R2H 2A6, Winnipeg, MB, Canada.
Prostaglandins Leukot Essent Fatty Acids. 2025 Oct;206:102697. doi: 10.1016/j.plefa.2025.102697. Epub 2025 Jun 27.
The ways in which diet and sex influence heart phospholipase A (PLA) activities are underexplored, particularly with respect to effects on oxylipin formation. Therefore, male and female Sprague-Dawley rats were provided diets with 1.3 % α-linolenic acid (ALA) or docosahexaenoic acid (DHA) for 6 weeks, and heart homogenates were incubated with inhibitors for secreted (s)PLA (Varespladib) or calcium-independent (i)PLA (methyl arachidonyl fluorophosphonate). Non-esterified polyunsaturated fatty acids (PUFA) and oxylipins were determined by HPLC-MS/MS and data were analyzed using 3-way repeated measures ANOVA. sPLA activity was selective for DHA release and DHA oxylipin formation, and contributed to ∼50 % of arachidonic acid (ARA) release, but only ∼30 % of ARA oxylipin formation. Eicosapentaenoic acid (EPA) release and oxylipin formation was minor but primarily mediated by iPLA. iPLA activity was less selective, with activity towards all measured PUFA and oxylipins, with the primary PUFA released depending on diet. For both sPLA and iPLA, there was more activity towards DHA and its oxylipins with the DHA diet, and towards ALA and ARA and their oxylipins with the ALA diet. Sex effects on fatty acids and oxylipins differed, as DHA, EPA and ALA release were higher in females, while DGLA and cyclooxygenase-derived ARA oxylipin formation were higher in males. Interestingly, the sex effect on cyclooxygenase ARA oxylipins was attenuated with dietary DHA. These findings provide further rationale for the simultaneous measurement of PUFA and oxylipins since they are not always congruent, and shed new light on diet and sex effects on PLA types in cardiovascular oxylipin biology.
饮食和性别对心脏磷脂酶A（PLA）活性的影响尚未得到充分研究，尤其是对氧化脂质形成的影响。因此，给雄性和雌性Sprague-Dawley大鼠喂食含1.3%α-亚麻酸（ALA）或二十二碳六烯酸（DHA）的饮食6周，然后将心脏匀浆与分泌型（s）PLA抑制剂（伐雷拉地布）或钙非依赖性（i）PLA抑制剂（甲基花生四烯酰氟磷酸酯）一起孵育。通过高效液相色谱-串联质谱法测定非酯化多不饱和脂肪酸（PUFA）和氧化脂质，并使用三因素重复测量方差分析对数据进行分析。sPLA活性对DHA释放和DHA氧化脂质形成具有选择性，促成了约50%的花生四烯酸（ARA）释放，但仅促成了约30%的ARA氧化脂质形成。二十碳五烯酸（EPA）释放和氧化脂质形成较少，但主要由iPLA介导。iPLA活性的选择性较低，对所有测量的PUFA和氧化脂质都有活性，释放的主要PUFA取决于饮食。对于sPLA和iPLA，DHA饮食对DHA及其氧化脂质的活性更高，而ALA饮食对ALA和ARA及其氧化脂质的活性更高。性别对脂肪酸和氧化脂质的影响不同，因为雌性中DHA、EPA和ALA的释放较高，而雄性中二高γ-亚麻酸（DGLA）和环氧化酶衍生的ARA氧化脂质形成较高。有趣的是，饮食中的DHA减弱了性别对环氧化酶ARA氧化脂质的影响。这些发现为同时测量PUFA和氧化脂质提供了进一步的理论依据，因为它们并不总是一致的，并且为饮食和性别对心血管氧化脂质生物学中PLA类型的影响提供了新的见解。
