靶向脂质组学表明，膳食LA/n-3 PUFAs通过氧化脂素调节双壳类动物的炎症和氧化还原状态。

IF 3.9 2区生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Biochimica et biophysica acta. Molecular and cell biology of lipids Pub Date : 2025-05-14 DOI:10.1016/j.bbalip.2025.159631

Yuxiang Zhu , Kai Liao , Yang Liu , Hailong Huang , Yang Zhang , Hui Ge , Deshui Chen , Bin Ma , Jilin Xu

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引用次数: 0

摘要

氧脂素是从脂肪酸中提取的生物活性脂质介质；然而，在双壳类动物中缺乏对氧脂质谱的全面研究。此外，pufa衍生的氧化脂类的生理功能和生物活性有待进一步研究。本研究发现，在过氧化氢（H2O2）胁迫下，饲料中添加适量的亚油酸/n-3 PUFAs可促进缢蛏的生长，提高其存活率。靶向脂质组学表明，高LA饮食增加了LA和LA衍生的氧化脂质的积累。有趣的是，在α-亚麻酸（ALA）和ALA衍生的氧化脂类中也观察到类似的模式，这可能有助于这种饮食模式的抗炎和抗氧化作用。然而，饮食中的n-3 PUFAs对h2o2引起的损伤提供了更大的保护。饲粮n-3 PUFAs显著提高了二十二碳六烯酸和二十碳五烯酸衍生的氧脂素水平，尤其是14(S)-羟基二十二碳六烯酸（14(S)-HDHA）和12-羟基二十碳五烯酸（12-HEPE）。此外，14(S)-HDHA和12-HEPE可以恢复过氧化氢（H2O2）处理的RAW264.7细胞的活力。在机制上，12-HEPE抑制核因子κB （NF-κB）的核易位，同时促进核因子红系2相关因子2 （Nrf2）的核易位，从而减轻炎症反应，增强抗氧化能力。此外，12-HEPE提高了蛤血淋巴细胞的抗氧化活性，抑制了炎症基因的表达。这项研究首次全面评估了双壳类动物的氧化脂质分布，进一步强调了饮食中n-3 pufa摄入对形成n-3 pufa衍生的氧化脂质的重要性，从而影响炎症和氧化还原状态。此外，我们的研究发现，12-HEPE减轻H2O2诱导的细胞损伤，NF-κB和Nrf2是关键途径。

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Targeted lipidomic reveals dietary LA/n-3 PUFAs regulate inflammation and redox status via oxylipins in bivalves

Oxylipins are bioactive lipid mediators derived from fatty acids; however, a comprehensive investigation of oxylipin profiles is absent in bivalves. Moreover, the physiological functions and bioactivities of PUFA-derived oxylipins warrant further exploration. In this study, we found that appropriate dietary linoleic acid (LA)/n-3 PUFAs enhanced the growth of the clam Sinonovacula constricta and improved its survival under hydrogen peroxide (H₂O₂) stress. Targeted lipidomic showed that the high-LA diet increased accumulation of LA and LA-derived oxylipins. Interestingly, a similar pattern was observed for α-linolenic acid (ALA) and ALA-derived oxylipins, potentially contributing to the anti-inflammatory and antioxidant effects of this dietary pattern. However, dietary n-3 PUFAs provided greater protection against H₂O₂-induced damage. Dietary n-3 PUFAs significantly increased the levels of oxylipins derived from docosahexaenoic acid and eicosapentaenoic acid, particularly 14(S)-hydroxydocosahexaenoic acid (14(S)-HDHA) and 12-hydroxyeicosapentaenoic acid (12-HEPE). Furthermore, 14(S)-HDHA and 12-HEPE restored cell viability in hydrogen peroxide (H₂O₂)-treated RAW264.7 cells. Mechanistically, 12-HEPE inhibited nuclear factor kappa B (NF-κB) nuclear translocation while promoting nuclear translocation of nuclear factor erythroid 2-related factor 2 (Nrf2), thereby reducing inflammatory responses and enhancing antioxidant capacity. Additionally, 12-HEPE increased antioxidant activity and suppressed inflammatory gene expression in clam hemolymph cells. This study represents the first comprehensive evaluation of the oxylipin profile in bivalves, further emphasizing the importance of dietary n-3 PUFAs intake in shaping n-3 PUFA-derived oxylipins and consequently influencing inflammation and redox status. Additionally, our study revealed that 12-HEPE alleviates cell damage induced by H₂O₂, with NF-κB and Nrf2 being key pathways.

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来源期刊

Biochimica et biophysica acta. Molecular and cell biology of lipids 生物-生化与分子生物学

CiteScore

11.00

自引率

2.10%

发文量

109

审稿时长

53 days

期刊介绍： BBA Molecular and Cell Biology of Lipids publishes papers on original research dealing with novel aspects of molecular genetics related to the lipidome, the biosynthesis of lipids, the role of lipids in cells and whole organisms, the regulation of lipid metabolism and function, and lipidomics in all organisms. Manuscripts should significantly advance the understanding of the molecular mechanisms underlying biological processes in which lipids are involved. Papers detailing novel methodology must report significant biochemical, molecular, or functional insight in the area of lipids.