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共轭亚油酸异构体c9,t11和t10,c12对活化的BV-2小胶质细胞的抗神经炎症作用。

Anti-neuroinflammatory effects of conjugated linoleic acid isomers, c9,t11 and t10,c12, on activated BV-2 microglial cells.

作者信息

Porcedda Clara, Manca Claudia, Carta Gianfranca, Piras Franca, Banni Sebastiano, Sogos Valeria, Murru Elisabetta

机构信息

Department of Biomedical Sciences, University of Cagliari, Monserrato, Italy.

出版信息

Front Cell Neurosci. 2024 Sep 27;18:1442786. doi: 10.3389/fncel.2024.1442786. eCollection 2024.

DOI:10.3389/fncel.2024.1442786
PMID:39398647
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11466893/
Abstract

Conjugated linoleic acid (CLA) isomers exhibit anti-inflammatory properties within the central nervous system (CNS). This study investigated the effects of CLA isomers c9,t11 and t10,c12 on fatty acid (FA) and acylethanolamine (NAE) profiles and their association with pro-inflammatory molecule expression in BV-2 microglia cell line, the CNS's resident immune cells responsible for maintaining neuronal activity and immune homeostasis. BV-2 cells were treated with 25 μM of c9,t11-CLA, t10,c12-CLA, or oleic acid (OA) for 24 h, followed by lipopolysaccharide (LPS) stimulation. After treatment, the cell's FA and NAE profiles and pro-inflammatory molecule expression were analyzed. Our results demonstrated that CLA isomers mitigate LPS-induced morphological changes in BV-2 cells and reduce gene expression and protein levels of inflammatory markers. This effect was linked to an upregulation of acyl-CoA oxidase 1, a key enzyme in the anti-inflammatory peroxisomal beta-oxidation pathway that efficiently metabolizes CLA isomers. Notably, t10,c12-CLA significantly suppressed stearoyl-CoA desaturase 1, impacting monounsaturated fatty acid synthesis. The NAEs profile was remarkably altered by CLA isomers, with a significant release of the anti-neuroinflammatory mediator docosahexaenoic acid (DHA)-derived acylethanolamine (DHAEA). In conclusion, our findings suggest that the anti-neuroinflammatory effects of CLA isomers are due to their unique influences on FA metabolism and the modulation of bioactive FA-derived NAEs, highlighting a potential strategy for nutritional intervention in conditions characterized by neuroinflammation.

摘要

共轭亚油酸（CLA）异构体在中枢神经系统（CNS）中具有抗炎特性。本研究调查了CLA异构体c9,t11和t10,c12对脂肪酸（FA）和酰基乙醇胺（NAE）谱的影响，以及它们与BV-2小胶质细胞系中促炎分子表达的关联。BV-2小胶质细胞系是中枢神经系统中的常驻免疫细胞，负责维持神经元活动和免疫稳态。用25μM的c9,t11-CLA、t10,c12-CLA或油酸（OA）处理BV-2细胞24小时，随后进行脂多糖（LPS）刺激。处理后，分析细胞的FA和NAE谱以及促炎分子表达。我们的结果表明，CLA异构体可减轻LPS诱导的BV-2细胞形态变化，并降低炎症标志物的基因表达和蛋白质水平。这种作用与酰基辅酶A氧化酶1的上调有关，酰基辅酶A氧化酶1是抗炎过氧化物酶体β-氧化途径中的关键酶，可有效代谢CLA异构体。值得注意的是，t10,c12-CLA显著抑制硬脂酰辅酶A去饱和酶1，影响单不饱和脂肪酸的合成。CLA异构体显著改变了NAE谱，抗神经炎症介质二十二碳六烯酸（DHA）衍生的酰基乙醇胺（DHAEA）大量释放。总之，我们的研究结果表明，CLA异构体的抗神经炎症作用归因于它们对FA代谢的独特影响以及对生物活性FA衍生的NAE的调节，突出了在以神经炎症为特征的疾病中进行营养干预的潜在策略。

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本文引用的文献

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Front Mol Neurosci. 2023 Dec 18;16:1299314. doi: 10.3389/fnmol.2023.1299314. eCollection 2023.
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Potential of omega-3 and conjugated fatty acids to control microglia inflammatory imbalance elicited by obesogenic nutrients.ω-3 和共轭脂肪酸控制肥胖营养物引发的小胶质细胞炎症失衡的潜力。
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Oleoylethanolamide Protects against Acute Ischemic Stroke by Promoting PPARα-Mediated Microglia/Macrophage M2 Polarization.
油酰乙醇胺通过促进PPARα介导的小胶质细胞/巨噬细胞M2极化来预防急性缺血性中风。
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The effects of conjugated linoleic acid supplementation on inflammatory cytokines and adipokines in adults: A GRADE-assessed systematic review and dose-response meta-analysis.共轭亚油酸补充剂对成年人炎症细胞因子和脂肪因子的影响：一项 GRADE 评估的系统评价和剂量反应荟萃分析。
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Staged suppression of microglial autophagy facilitates regeneration in CNS demyelination by enhancing the production of linoleic acid.分期抑制小胶质细胞自噬通过增加亚油酸的产生促进中枢神经系统脱髓鞘的再生。
Proc Natl Acad Sci U S A. 2023 Jan 3;120(1):e2209990120. doi: 10.1073/pnas.2209990120. Epub 2022 Dec 28.
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Cells. 2022 Jun 30;11(13):2091. doi: 10.3390/cells11132091.
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