Prostaglandins, leukotrienes, and essential fatty acids最新文献_第4页

HYPOTHESIS: Lipid-protecting disulfide bridges are the missing molecular link between ApoE4 and sporadic Alzheimer's disease in humans 假设：保护脂质的二硫桥是ApoE4与人类散发性阿尔茨海默病之间缺失的分子联系

IF 3

Prostaglandins, leukotrienes, and essential fatty acids

Pub Date : 2025-07-01 Epub Date: 2025-04-03 DOI: 10.1016/j.plefa.2025.102681

Christopher E. Ramsden , Roy G. Cutler , Xiufeng Li , Gregory S. Keyes

As the principal lipid transporter in the human brain, apolipoprotein E (ApoE) is tasked with transport and protection of highly vulnerable lipids that are required to support and remodel neuronal membranes, in a process that is dependent on ApoE receptors. APOE allele variants that encode proteins differing only in the number of cysteine (Cys)-to-arginine (Arg) exchanges (ApoE2 [2 Cys], ApoE3 [1 Cys], ApoE4 [0 Cys]) comprise the strongest genetic risk factor for sporadic Alzheimer's disease (AD); however, the specific molecular feature(s) and resultant mechanisms that underlie these isoform-dependent effects are unknown. One signature feature of Cys is the capacity to form disulfide (Cys-Cys) bridges, which are required to form disulfide-linked dimers and multimers. Here we propose the overarching hypothesis that super-ability (for ApoE2), intermediate ability (for ApoE3) or inability (for ApoE4) to form lipid-protecting intermolecular disulfide bridges, is the central molecular determinant accounting for the disparate effects of APOE alleles on AD risk and amyloid-β and Tau pathologies in humans. We posit that presence and abundance of Cys in human ApoE3 and ApoE2 respectively, conceal and protect vulnerable lipids transported by ApoE from peroxidation by enabling formation of disulfide-linked homo- and heteromeric ApoE complexes. We thus propose that inability to form intermolecular disulfide bridges makes ApoE4-containing lipoproteins uniquely vulnerable to peroxidation and its downstream consequences. Consistent with our model, we found that brain-enriched polyunsaturated fatty acid-containing phospholipids induce disulfide-dependent dimerization and multimerization of ApoE3 and ApoE2 (but not ApoE4). By contrast, incubation with the peroxidation-resistant lipid DMPC or cholesterol alone had minimal effects on dimerization. These novel concepts and findings are integrated into our unifying model implicating peroxidation of ApoE-containing lipoproteins, with consequent ApoE receptor-ligand disruption, as initiating molecular events that ultimately lead to AD in humans.

作为人脑中主要的脂质转运体，载脂蛋白E （ApoE）的任务是运输和保护高度脆弱的脂质，这些脂质是支持和重塑神经元膜所必需的，这一过程依赖于载脂蛋白E受体。APOE等位基因变异编码的蛋白质仅在半胱氨酸（Cys）与精氨酸（Arg）交换的数量上不同（ApoE2 [2 Cys], ApoE3 [1 Cys], ApoE4 [0 Cys]），是散发性阿尔茨海默病（AD）的最强遗传危险因素；然而，这些异构体依赖效应的具体分子特征和产生机制尚不清楚。Cys的一个显著特征是能够形成二硫化物（Cys-Cys）桥，这是形成二硫化物连接的二聚体和多聚体所必需的。在这里，我们提出了一个总体假设，即APOE等位基因对人类AD风险和淀粉样蛋白β和Tau病理的不同影响，其形成脂质保护分子间二硫桥的超能力（ApoE2）、中等能力（ApoE3）或无能力（ApoE4）是主要的分子决定因素。我们假设，在人类ApoE3和ApoE2中分别存在和丰富的Cys，通过形成二硫化物连接的同源和异聚ApoE复合物，隐藏和保护ApoE运输的易感脂质免于过氧化。因此，我们提出无法形成分子间二硫桥使得含apoe4的脂蛋白特别容易受到过氧化及其下游后果的影响。与我们的模型一致，我们发现富含大脑的含多不饱和脂肪酸的磷脂诱导ApoE3和ApoE2的二聚和多聚（但不包括ApoE4）。相比之下，与抗过氧化脂质DMPC或胆固醇单独孵育对二聚化的影响最小。这些新颖的概念和发现被整合到我们的统一模型中，该模型暗示含ApoE的脂蛋白过氧化，随之而来的ApoE受体配体破坏，是最终导致人类AD的初始分子事件。

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引用次数: 0

The single-dose kinetics of [1–14C]-labelled EPA and DHA, administered to male rats as TAG, phosphatidylcholine (PC), and lyso-phosphatidylcholine (LPC), is structurally similar across lipid forms and can be described using the same compartmental models [1-14C]标记的EPA和DHA以TAG、磷脂酰胆碱（PC）和溶磷脂酰胆碱（LPC）的形式单剂量给予雄性大鼠，其结构在脂质形式上是相似的，可以用相同的室室模型来描述

IF 3

Prostaglandins, leukotrienes, and essential fatty acids

Pub Date : 2025-07-01 Epub Date: 2025-02-24 DOI: 10.1016/j.plefa.2025.102671

Nils Hoem , Stephen Harris , Grace Scott , Petter-Arnt Hals

To investigate the systemic kinetics of EPA and DHA across different lipid classes, male rats were administered [1–¹⁴C]-radiolabelled EPA and DHA as triglycerides (TAG), phosphatidylcholine (PC), or lyso-phosphatidylcholine (LPC) by gavage. LPC was also administered intravenously. Plasma and whole blood concentration-time profiles were recorded from 0 to 168 hours, while cumulative radioactivity in expired air, faeces, and urine was recorded for up to 336 hours.

Non-compartmental analysis and compartmental modelling demonstrated overall first-order radiotracer kinetics for both fatty acids, with comparable terminal half-lives. The primary difference was in maximum concentration (Cmax ((µg-eq/g)/(mg/kg)): DHA = 0.18± 0.089, EPA = 0.24± 0.103; P < 0.0001). Between TAG and PC, only time to maximum concentration (Tmax (h)) differed (PC = 3.23 ± 0.94, TAG = 2.55 ± 0.77; P = 0.0004). LPC showed significant differences from TAG and PC in area under the curve (AUC0-inf), Cmax, Tmax, and total clearance (CL/F (mL/(kg h))). Cumulative radioactivity levels in expired air and faeces were consistent with blood and plasma kinetics.

As suggested by early-phase (0 to 48 hours) radioactivity accumulation, which deviated from first-order behaviour, TAG and PC, but not LPC, exhibited some faecal loss without systemic absorption.

The compartmental models developed performed equally well for radiolabelled EPA and DHA, regardless of whether administered as TAG, PC, or LPC. The model can be adapted to handle non-zero endogenous baselines and was successfully applied to non-radiolabelled EPA, docosapentaenoic acid (DPA), and DHA, quantified via LC-MS/MS. These models can be applied to both radioactive and stable isotopes and adapted to include organ-specific kinetics, as well as those of EPA, DPA, and DHA in other species, including humans.

为了研究EPA和DHA在不同脂类中的全身动力学，雄性大鼠通过灌胃给予[1-14C]放射性标记的EPA和DHA作为甘油三酯（TAG）、磷脂酰胆碱（PC）或溶磷脂酰胆碱（LPC）。LPC也通过静脉注射。从0到168小时记录血浆和全血浓度-时间曲线，而在过期空气、粪便和尿液中记录累积放射性长达336小时。非区室分析和区室建模证明了这两种脂肪酸的总体一级放射性示踪动力学，具有相似的末端半衰期。最大浓度差异(Cmax（（µg-eq/g）/(mg/kg)）： DHA = 0.18±0.089,EPA = 0.24±0.103；P & lt;0.0001)。两组间仅达到最大浓度所需时间（Tmax (h)）有差异(PC = 3.23±0.94,TAG = 2.55±0.77；P = 0.0004)。在曲线下面积（AUC0-inf）、Cmax、Tmax和总清除率(CL/F （mL/(kg h)）方面，LPC与TAG和PC有显著差异。过期空气和粪便中的累积放射性水平与血液和血浆动力学一致。早期（0 ~ 48小时）放射性积累偏离一阶行为，TAG和PC，但LPC没有，表现出一些粪便损失，没有全身吸收。无论以TAG、PC还是LPC方式给药，所建立的室室模型对放射性标记的EPA和DHA表现同样良好。该模型可用于处理非零内源基线，并成功应用于非放射性标记的EPA、二十二碳五烯酸（DPA）和DHA，通过LC-MS/MS进行定量。这些模型可以应用于放射性和稳定同位素，并适应于包括器官特异性动力学，以及EPA， DPA和DHA在其他物种，包括人类中的动力学。

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引用次数: 0

Dihomo-gamma-linolenic acid (DGLA) is inversely related to risk for cardiac death and cardiovascular events during 2 years follow-up after admission for an acute coronary syndrome 急性冠状动脉综合征入院后2年随访期间，二同γ -亚麻酸（DGLA）与心源性死亡和心血管事件风险呈负相关

IF 3

Prostaglandins, leukotrienes, and essential fatty acids

Pub Date : 2025-07-01 Epub Date: 2025-04-10 DOI: 10.1016/j.plefa.2025.102684

Dennis W.T. Nilsen , Hildegunn Aarsetoey , Volker Poenitz , Trygve Brugger-Andersen , William S. Harris , Harry Staines , Heidi Grundt

Background/Aim

Dihomo-gamma-linolenic acid (DGLA) is derived from linoleic acid. Its presence in red blood cell (RBC) membranes is mainly due to metabolism and not diet. RBC DGLA was negatively associated with all-cause mortality during 7 years follow-up in patients admitted with an acute coronary syndrome (ACS). We now present its 2-year cardiovascular prognostic utility compared to other n-6 fatty acids (FAs).

Methods

A total of 139 females and 259 males with a mean age of 71.9 ± 13.0 years were admitted consecutively in this study. Stepwise Cox regression models, applying continuous values of DGLA weight percent (wt %) and quartiles, were fitted for the biomarkers with cardiac death and a combined cardiovascular (CV) endpoint consisting of cardiac death or myocardial infarction (MI) or stroke as the dependent variables.

Results

Cardiac death was recorded in 57 patients, and the composite CV endpoint in 144 patients, respectively. DGLA was negatively associated with both endpoints, each with a p-value of <0.001 in univariate analysis. The hazard ratio (HR, per 1 wt % increase) remained significant after multivariable adjustment [cardiac death HR 0.51 (95 %CI 0.27–0.98), p = 0.042, and composite CV endpoint HR 0.61 (95 %CI 0.41–0.92), p = 0.017]. A similar pattern was obtained in ACS patients presenting with an acute MI at admission.

No association with any outcome was found with the other n-6 FAs [linoleic acid, arachidonic acid and adrenic acid].

Conclusion

Higher RBC DGLA predicts lower risk for cardiac death and cardiovascular outcomes at 2 years follow-up in ACS patients, whereas other n-6 FAs do not.

Clinical trial registration: ClinicalTrials.gov Identifier: NCT00521976

二同γ -亚麻酸（DGLA）来源于亚油酸。它在红细胞（RBC）膜中的存在主要是由于代谢而不是饮食。在急性冠脉综合征（ACS）患者7年随访期间，RBC DGLA与全因死亡率呈负相关。我们现在将其与其他n-6脂肪酸（FAs）相比，在2年心血管预后方面的效用进行了介绍。方法本研究共收治女性139例，男性259例，平均年龄71.9±13.0岁。采用DGLA权重百分比（wt %）和四分位数连续值的逐步Cox回归模型，拟合心脏死亡和由心脏死亡或心肌梗死（MI）或中风组成的心血管（CV）联合终点作为因变量的生物标志物。结果心脏死亡57例，复合CV终点144例。DGLA与两个终点均呈负相关，在单变量分析中，每个终点的p值均为<；0.001。多变量校正后，风险比（HR，每增加1 wt %）仍然显著[心脏死亡HR 0.51 (95% CI 0.27-0.98), p = 0.042，复合CV终点HR 0.61 (95% CI 0.41-0.92), p = 0.017]。在入院时出现急性心肌梗死的ACS患者中也出现了类似的模式。其他n-6脂肪酸[亚油酸、花生四烯酸和肾上腺酸]与任何结果均无关联。结论：在ACS患者2年随访中，较高的RBC DGLA预示着较低的心源性死亡风险和心血管结局，而其他n-6 FAs则不然。临床试验注册：ClinicalTrials.gov标识符：NCT00521976

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引用次数: 0

LTB4 is converted into a potent human neutrophil NADPH oxidase activator via a receptor transactivation mechanism in which the BLT1 receptor activates the free fatty acid receptor 2 LTB4通过受体转激活机制转化为有效的人中性粒细胞NADPH氧化酶激活剂，其中BLT1受体激活游离脂肪酸受体2

IF 3

Prostaglandins, leukotrienes, and essential fatty acids

Pub Date : 2025-07-01 Epub Date: 2025-04-03 DOI: 10.1016/j.plefa.2025.102680

Yanling Wu , Claes Dahlgren , Huamei Forsman , Martina Sundqvist

The endogenous neutrophil chemoattractant leukotriene B₄ (LTB₄) is a biased signalling agonist that potently increases the intracellular concentration of free calcium ions ([Ca²⁺]_i), but alone is a weak activator of the neutrophil superoxide anion (O₂^-)-generating NADPH oxidase. However, in this study we show that an allosteric modulator of the free fatty acid 2 receptor (FFA2R) converts LTB₄ into a potent NADPH oxidase activating agonist. While an allosteric modulation of FFA2R was required for LTB₄ receptor 1 (BLT₁R)-mediated activation of the NADPH oxidase, the LTB₄-induced increase in [Ca²⁺]_i was not affected by the modulator. Thus, the biased BLT₁R signalling pattern was altered in the presence of the allosteric FFA2R modulator, being biased with a preference towards the signals that activate the NADPH oxidase relative to an increase in [Ca²⁺]_i. Both BLT₁R and FFA2R belong to the family of G protein-coupled receptors (GPCRs), and our results show that a communication between the activated BLT₁R and the allosterically modulated FFA2Rs generates signals that induce NADPH oxidase activity. This is consistent with a previously described receptor transactivation (crosstalk) model whereby the function of one neutrophil GPCR can be regulated by receptor downstream signals generated by another GPCR. Furthermore, the finding that an allosteric FFA2R modulator sensitises not only the response induced by orthosteric FFA2R agonists but also the response induced by LTB₄, violates the receptor restriction properties that normally define the selectivity of allosteric GPCR modulators.

内源性中性粒细胞趋化剂白三烯B4 （LTB4）是一种偏置信号激动剂，可有效增加细胞内游离钙离子（[Ca2+]i）的浓度，但单独是中性粒细胞超氧阴离子（O2-）生成NADPH氧化酶的弱激活剂。然而，在这项研究中，我们发现游离脂肪酸2受体（FFA2R）的变抗调节剂将LTB4转化为一种有效的NADPH氧化酶激活激动剂。虽然LTB4受体1 （BLT1R）介导的NADPH氧化酶激活需要对FFA2R进行变构调节，但LTB4诱导的[Ca2+]i的增加不受调节剂的影响。因此，在变弹性FFA2R调节剂的存在下，偏向的BLT1R信号模式发生了改变，相对于[Ca2+]i的增加，偏向于激活NADPH氧化酶的信号。BLT1R和FFA2R都属于G蛋白偶联受体（gpcr）家族，我们的研究结果表明，激活的BLT1R和变弹性调节的FFA2Rs之间的通信产生了诱导NADPH氧化酶活性的信号。这与先前描述的受体反激活（串扰）模型一致，其中一个中性粒细胞GPCR的功能可以由另一个GPCR产生的受体下游信号调节。此外，发现变构性FFA2R调节剂不仅使正构性FFA2R激动剂诱导的反应敏感，而且使LTB4诱导的反应敏感，这违反了通常定义变构性GPCR调节剂选择性的受体限制特性。

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引用次数: 0

Plasma saturated fatty acids are inversely associated with lean mass and strength in adults: NHANES 2011–2012 血浆饱和脂肪酸与成人瘦体重和力量呈负相关：NHANES 2011-2012

IF 3

Prostaglandins, leukotrienes, and essential fatty acids

Pub Date : 2025-04-01 Epub Date: 2025-01-30 DOI: 10.1016/j.plefa.2025.102667

Heitor O. Santos, Rafaela Nehme, Larissa S. Limirio, Maria Eduarda de F. Mendonça, Flávia M.S. de Branco, Erick P. de Oliveira

Background & aims

Several studies have suggested that increased intake of saturated fatty acids (SFAs) may have a pro-inflammatory effect, potentially impacting muscle mass and strength. However, the relationship of plasma SFAs and their subtypes (which reflect dietary SFA intake) with muscle mass and strength remains poorly understood. This study aimed to evaluate the association of plasma SFAs with lean mass and handgrip strength in adults.

Methods

A cross-sectional study was conducted with 896 participants aged 20-59 years, selected from a subsample of the National Health and Nutrition Examination Survey (NHANES) 2011–2012. Total plasma SFAs and their subtypes were detected using gas chromatography-mass spectrometry. Lean mass was assessed using dual-energy X-ray absorptiometry, with evaluations of both total lean mass and appendicular lean mass. Muscle strength was measured using a handgrip dynamometer, with combined grip strength calculated by summing the highest values from each hand. Linear regression analysis was conducted to examine the association between plasma SFAs, lean mass, and handgrip strength, adjusting for potential confounders.

Results

Total lean mass was negatively associated with total plasma SFAs and several of their subtypes such as plasma levels of stearic acid, palmitic acid, arachidic acid, tricosanoic acid, lignoceric acid, and docosanoic acid. Similarly, appendicular lean mass was negatively associated with total plasma SFAs, as well as with several specific subtypes, including palmitic acid, stearic acid, margaric acid, pentadecanoic acid, and myristic acid. Handgrip strength also demonstrated a negative association with total plasma SFAs, including specific subtypes such as lauric acid, palmitic acid, capric acid, margaric acid, pentadecanoic acid, and myristic acid.

Conclusion

Total plasma SFAs and several of their subtypes are inversely associated with lean mass and muscle strength in adults.

背景,几项研究表明，饱和脂肪酸（sfa）摄入量的增加可能具有促炎作用，可能会影响肌肉质量和力量。然而，血浆SFA及其亚型（反映膳食SFA摄入量）与肌肉质量和力量的关系仍然知之甚少。本研究旨在评估成人血浆sfa与瘦体重和握力的关系。方法选取2011-2012年国家健康与营养调查（NHANES）的子样本，对896名年龄在20-59岁之间的参与者进行横断面研究。采用气相色谱-质谱法检测血浆总sfa及其亚型。采用双能x线吸收仪评估瘦质量，同时评估总瘦质量和阑尾瘦质量。肌肉力量是用握力计测量的，通过将每只手的最大值相加来计算综合握力。进行线性回归分析以检验血浆sfa、瘦质量和握力之间的关系，并对潜在的混杂因素进行调整。结果总瘦体重与血浆总sfa及其几个亚型（硬脂酸、棕榈酸、花生四酸、三糖酸、木质素酸和二十二糖酸）水平呈负相关。同样，阑尾瘦质量与血浆总sfa以及几种特定亚型呈负相关，包括棕榈酸、硬脂酸、人造黄油酸、棕榈酸和肉豆汁酸。握力也与血浆总sfa呈负相关，包括特定亚型，如月桂酸、棕榈酸、癸酸、人造黄油酸、五酸和肉豆酱酸。结论血浆总sfa及其几种亚型与成人瘦质量和肌力呈负相关。

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引用次数: 0

Association between the COX-2 rs689466 polymorphism and antipsychotic treatment: Impact on HDL cholesterol changes in clozapine-treated psychosis patients COX-2 rs689466多态性与抗精神病治疗的关系：对氯氮平治疗精神病患者HDL胆固醇变化的影响

IF 3

Prostaglandins, leukotrienes, and essential fatty acids

Pub Date : 2025-04-01 Epub Date: 2025-01-29 DOI: 10.1016/j.plefa.2025.102665

Sergej Nadalin , Ivan Ljoka , Aleksandar Savić , Ante Silić , Vjekoslav Peitl , Dalibor Karlović , Maja Vilibić , Lena Zatković , Alena Buretić-Tomljanović

Several studies have shown antipsychotic effects of the selective cyclooxygenase-2 (COX-2) inhibitor celecoxib as an add-on treatment to antipsychotic treatment. The functional rs689466 (A/G) polymorphism in the gene encoding COX-2 (also known as the prostaglandin-endoperoxide synthase 2 gene) has been correlated with schizophrenia risk and the niacin skin flush response among chronic patients under antipsychotic treatment. Here, we investigated whether this polymorphism was associated with antipsychotic treatment in a group of total psychosis patients (N = 186), as well as a subgroup of patients treated with clozapine (N = 74). Antipsychotic-naïve first-episode patients and non-adherent chronic psychosis patients were genotyped by polymerase chain reaction/restriction fragment length polymorphism analysis. At baseline and after 8 weeks of treatment with various antipsychotic medications, we assessed the patients’ Positive and Negative Syndrome Scale (PANSS) scores, factors, and metabolic syndrome-related parameters, including fasting plasma lipid and glucose levels and body mass index. In the total patient group, the COX-2 polymorphism was not associated with PANSS psychopathology scores or metabolic parameters. However, in the subgroup of patients treated with clozapine, the COX-2 polymorphism was associated with changes in plasma HDL cholesterol. Specifically, compared to patients homozygous for the A allele, the subgroup of patients treated with clozapine and positive for the G allele (i.e., GG or AG genotype) exhibited significantly higher increases in HDL cholesterol levels. The COX-2 polymorphism had a moderate effect size but made a relatively weak contribution to variations in the HDL cholesterol level (∼9.6 %).

一些研究表明选择性环氧化酶-2 （COX-2）抑制剂塞来昔布作为抗精神病治疗的附加治疗具有抗精神病作用。编码COX-2（也称为前列腺素内过氧化物合成酶2基因）的基因rs689466 （A/G）多态性与接受抗精神病药物治疗的慢性患者的精神分裂症风险和烟酸皮肤潮红反应相关。在这里，我们研究了这种多态性是否与一组全精神病患者（N = 186）以及一组接受氯氮平治疗的患者（N = 74）的抗精神病药物治疗有关。Antipsychotic-naïve首发患者和非依从性慢性精神病患者采用聚合酶链反应/限制性片段长度多态性分析进行基因分型。在基线和使用各种抗精神病药物治疗8周后，我们评估了患者的阳性和阴性综合征量表（PANSS）评分、因素和代谢综合征相关参数，包括空腹血脂和血糖水平以及体重指数。在整个患者组中，COX-2多态性与PANSS精神病理评分或代谢参数无关。然而，在接受氯氮平治疗的患者亚组中，COX-2多态性与血浆高密度脂蛋白胆固醇的变化有关。具体来说，与A等位基因纯合子的患者相比，接受氯氮平治疗且G等位基因阳性（即GG或AG基因型）的患者亚组的HDL胆固醇水平明显升高。COX-2多态性具有中等效应大小，但对HDL胆固醇水平的影响相对较弱（约9.6%）。

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引用次数: 0

Brain region and sex-dependent heterogeneity of PUFA/oxylipin profile, microglia morphology and their relationship 脑区和性别依赖性PUFA/氧化脂质谱异质性、小胶质细胞形态及其关系。

IF 3

Prostaglandins, leukotrienes, and essential fatty acids

Pub Date : 2025-04-01 Epub Date: 2024-12-16 DOI: 10.1016/j.plefa.2024.102662

J. Geertsema , M.A. Franßen , F. Barban , L. Šarauskytė , M. Giera , G. Kooij , A Korosi

Lipid dyshomeostasis and neuroinflammation are key hallmarks of neuropsychiatric and neurodegenerative disorders, including major depressive disorder and Alzheimer's disease. In particular, polyunsaturated fatty acids (PUFAs) and their derivatives called oxylipins gained specific interest in this context, especially considering their capacity to orchestrate neuroinflammatory responses via direct modulation of microglia. The hippocampus and hypothalamus are crucial brain regions for regulating mood and cognition that are implicated in a variety of neuropsychiatric and neurodegenerative disorders and there is ample evidence for the sex-bias in risks for the development as well as sex-bias in the presentation of such psychiatric diseases, including the neuroinflammatory response. To better understand the local PUFA/oxylipin profiles and microglia responses in disease, we here assessed their brain region and sex-dependent profiles in homeostatic brains. In 2-month-old male and female mice, we measured non-esterified (free) PUFA/oxylipin profiles using liquid chromatography-tandem mass spectrometry and characterized microglia morphology via immunohistochemistry. The hypothalamus and hippocampus exhibit a different free PUFA/oxylipin profile, independent of sex. The hippocampus was characterized by a higher density of complex Iba1⁺ microglial cells than the hypothalamus, without sex effects. Hypothalamic microglial morphology correlated more strongly with free PUFA- and oxylipin species than hippocampal microglia, correlating with species from both the N-3 and N-6 PUFA metabolization pathways, while hippocampal microglial parameters correlated only with N-6 pathway-related species. Our findings provide a basis for future studies to investigate the relationship between PUFAs, their derivatives and neuroinflammation in the context of diseases.

脂质失衡和神经炎症是神经精神和神经退行性疾病的关键标志，包括重度抑郁症和阿尔茨海默病。特别是，多不饱和脂肪酸（PUFAs）及其衍生物氧脂素在这方面获得了特别的兴趣，特别是考虑到它们通过直接调节小胶质细胞来协调神经炎症反应的能力。海马体和下丘脑是调节情绪和认知的关键大脑区域，与各种神经精神和神经退行性疾病有关，有充分的证据表明，在这些精神疾病的发展风险和表现中存在性别偏见，包括神经炎症反应。为了更好地了解局部PUFA/oxylipin谱和疾病中的小胶质细胞反应，我们在这里评估了它们在体内平衡大脑中的脑区域和性别依赖谱。在2个月大的雄性和雌性小鼠中，我们使用液相色谱-串联质谱法测量了非酯化（游离）PUFA/氧脂质谱，并通过免疫组织化学表征了小胶质细胞的形态。下丘脑和海马体表现出不同的游离PUFA/氧化脂质谱，与性别无关。海马的特点是复杂的Iba1+小胶质细胞比下丘脑密度更高，没有性别效应。下丘脑小胶质细胞形态与游离PUFA和氧化脂质的相关性比海马小胶质细胞更强，与N-3和N-6 PUFA代谢途径的物种相关，而海马小胶质细胞参数仅与N-6途径相关。我们的发现为进一步研究PUFAs及其衍生物与疾病背景下神经炎症之间的关系提供了基础。

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引用次数: 0

The effect of long-chain n-3 PUFA on liver transcriptome in human obesity 长链n-3 PUFA对肥胖人群肝脏转录组的影响。

IF 3

Prostaglandins, leukotrienes, and essential fatty acids

Pub Date : 2025-04-01 Epub Date: 2024-12-12 DOI: 10.1016/j.plefa.2024.102663

Rebeka Joerg , Bianca K. Itariu , Melina Amor , Martin Bilban , Felix Langer , Gerhard Prager , Florian Joerg , Thomas M. Stulnig

Background and aims

Obesity is associated with a higher risk of severe diseases such as atherosclerotic cardiovascular disease, type 2 diabetes mellitus (T2DM), and metabolic dysfunction-associated steatotic liver disease (MASLD). Polyunsaturated fatty acids, of the omega-3 family (n-3 PUFA), have been shown to reduce adipose tissue inflammation in obesity, as well as to have lipid-lowering effects and improve insulin sensitivity. However, direct effects on liver transcriptome in humans have not been described. Our aim was to understand the impact of n-3 PUFA on gene expression in obese human liver.

Approach and Results

Patients with obesity (BMI

\geq

40 kg/m²) were treated for eight weeks with 3.36 g n-3 PUFAs (1.84 g eicosapentaenoic acid (EPA) and 1.53 g docosahexaenoic acid (DHA)), or with 5 g of butter as a control (n = 15 per group) before undergoing bariatric surgery where liver biopsies were taken. Liver samples were used for mRNA microarray analyses and subsequently Gene Set Enrichment Analysis (GSEA) was performed. This bioinformatic approach led us to identify 80 significantly dysregulated pathways that were divided into 9 different clusters including insulin and lipid metabolism, and immunity. N-3 PUFA treatment significantly affected pathways related to immunity, metabolism, and inflammation. Specifically, it upregulated pathways involved in T-cell and B-cell functions and lipid metabolism, while downregulating glucagon signalling. These findings highlight the impact of n-3 PUFAs on key metabolic and immune processes in the liver of patients with obesity.

Conclusion

This study provides further insights into the impact on n-3 PUFA on human liver gene expression, particularly in pathways associated with immunity, lipid metabolism, and inflammation, setting basis for further clinical research.

Summary

Obesity increases the risk of diseases like atherosclerotic- cardiovascular disease, type 2 diabetes mellitus and metabolic dysfunction-associated steatotic liver disease (MASLD). Omega-3 polyunsaturated fatty acids (n-3 PUFA) are known for their anti-inflammatory and metabolic benefits, but their direct impact on liver gene expression in people with obesity, remains unclear. In this study, patients with obesity (BMI ≥ 40 kg/m2) were administered either n-3 PUFAs or butter before bariatric surgery. Liver biopsies were analysed for gene expression via Gene Set Enrichment Analysis (GSEA). The results revealed 80 dysregulated pathways across 9 clusters, including those related to insulin and lipid metabolism, and immunity. This sheds light on how n-3 PUFAs influence gene expression in the liver of patients with obesity, setting the groundwork for further clinical exploration.

背景和目的：肥胖与严重疾病的高风险相关，如动脉粥样硬化性心血管疾病、2型糖尿病（T2DM）和代谢功能障碍相关的脂肪变性肝病（MASLD）。omega-3家族的多不饱和脂肪酸（n-3 PUFA）已被证明可以减少肥胖的脂肪组织炎症，以及具有降脂作用和改善胰岛素敏感性。然而，对人类肝脏转录组的直接影响尚未被描述。我们的目的是了解n-3 PUFA对肥胖人类肝脏基因表达的影响。方法和结果：肥胖患者（BMI≥40 kg/m2）接受3.36 g n-3 PUFAs （1.84 g二十碳五烯酸（EPA）和1.53 g二十二碳六烯酸（DHA））或5 g黄油作为对照（每组n = 15）治疗8周，然后进行减肥手术，并进行肝活检。肝脏样本用于mRNA微阵列分析，随后进行基因集富集分析（GSEA）。这种生物信息学方法使我们确定了80个显着失调的途径，这些途径分为9个不同的簇，包括胰岛素和脂质代谢以及免疫。N-3 PUFA治疗显著影响与免疫、代谢和炎症相关的途径。具体来说，它上调了t细胞和b细胞功能和脂质代谢的通路，同时下调了胰高血糖素信号传导。这些发现强调了n-3 PUFAs对肥胖患者肝脏关键代谢和免疫过程的影响。结论：本研究进一步揭示了n-3 PUFA对人肝脏基因表达的影响，特别是对免疫、脂质代谢和炎症相关通路的影响，为进一步的临床研究奠定了基础。总结：肥胖增加了动脉粥样硬化性心血管疾病、2型糖尿病和代谢功能障碍相关脂肪变性肝病（MASLD）等疾病的风险。Omega-3多不饱和脂肪酸（n-3 PUFA）因其抗炎和代谢益处而闻名，但其对肥胖人群肝脏基因表达的直接影响尚不清楚。在这项研究中，肥胖患者（BMI≥40 kg/m2）在减肥手术前给予n-3 PUFAs或黄油。通过基因集富集分析（GSEA）对肝活检组织进行基因表达分析。结果显示，在9个簇中有80条通路失调，包括与胰岛素和脂质代谢以及免疫相关的通路。这揭示了n-3 PUFAs如何影响肥胖患者肝脏中的基因表达，为进一步的临床探索奠定了基础。

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引用次数: 0

Effects of seal oil supplementation on lipid profile biomarkers: A systematic review and meta-analysis of randomized controlled trials 海豹油补充对脂质生物标志物的影响：随机对照试验的系统回顾和荟萃分析

IF 3

Prostaglandins, leukotrienes, and essential fatty acids

Pub Date : 2025-04-01 Epub Date: 2025-01-29 DOI: 10.1016/j.plefa.2025.102666

Mariano Gallo Ruelas , Ivo Queiroz , Túlio Pimentel , Arthur Henrique Tavares , Maria L.R. Defante , Lucas M. Barbosa , Igor Eckert

Background

Seal oil (SO) supplementation has been purported to have cardiovascular health benefits due to its content of omega-3 fatty acids; however, the clinical evidence base for this intervention has yet to be comprehensively assessed.

Objective

We aimed to evaluate the effects of oral SO supplementation on lipid profile biomarkers.

Methods

A systematic search was performed on Pubmed, Embase, Web of Science and Cochrane Library, from inception to August 2024. Only randomized controlled trials (RCTs) assessing the effect of SO on lipid profile biomarkers were included. A random-effects meta-analysis was applied to determine the overall effect estimate. The certainty of evidence (CoE) was evaluated using the GRADE approach.

Results

Nine RCTs were included in the review after the screening of 242 studies, comprising a total of 626 patients. Supplementation of SO resulted in no statistically significant effects on LDL-C (MD -0.07 mmol/L; 95 % CI [-0.19, 0.05]; CoE: Low) and total cholesterol (MD -0.12 mmol/L; 95 % CI [-0.30, 0.06]; CoE: Very low). There were statistically significant results of modest-to-trivial clinical importance on triglycerides (MD -0.19 mmol/L, 95 % CI [-0.30, -0.08]; CoE: Low) and trivial importance on HDL-C (MD 0.07 mmol/L, 95 % CI [0.003, 0.13]; CoE: Very low).

Conclusion

There is no sufficiently certain evidence to determine the effects of SO on cardiovascular lipid biomarkers. Our analyses may suggest a modest-to-trivial, clinically uncertain beneficial effect on triglyceride levels; and little to no effect on LDL-C. Effect estimates for HDL-C and total cholesterol levels were highly uncertain. Further evidence is required to conclusively determine the effects of oral SO on lipid biomarkers.

Protocol registration number

CRD42024583739

海豹油（SO）补充剂被认为对心血管健康有益，因为它含有omega-3脂肪酸；然而，这种干预的临床证据基础尚未得到全面评估。目的评价口服SO补充剂对血脂生物标志物的影响。方法系统检索Pubmed、Embase、Web of Science和Cochrane Library，检索时间为建站至2024年8月。仅纳入了评估SO对血脂生物标志物影响的随机对照试验（rct）。采用随机效应荟萃分析确定总体效应估计。使用GRADE方法评估证据的确定性（CoE）。结果在242项研究筛选后，纳入9项rct，共纳入626例患者。补充SO对LDL-C的影响无统计学意义(MD -0.07 mmol/L；95% ci [-0.19, 0.05]；CoE：低)和总胆固醇(MD -0.12 mmol/L；95% ci [-0.30, 0.06]；CoE：非常低)。甘油三酯的临床重要性有统计学意义（MD -0.19 mmol/L, 95% CI [-0.30, -0.08]）；CoE：低)，对HDL-C不重要(MD 0.07 mmol/L, 95% CI [0.003, 0.13]；CoE：非常低)。结论目前尚没有足够的证据表明大豆油对心血管脂质生物标志物的影响。我们的分析可能表明对甘油三酯水平有轻微到微不足道的、临床不确定的有益影响；对LDL-C几乎没有影响对HDL-C和总胆固醇水平的影响估计高度不确定。需要进一步的证据来确定口服SO对脂质生物标志物的影响。协议注册号crd42024583739

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引用次数: 0

Depression and anxiety in the pregnant Omani population in relation to their fatty acid intake and levels 阿曼孕妇的抑郁和焦虑与脂肪酸摄入量和水平的关系

IF 3

Prostaglandins, leukotrienes, and essential fatty acids

Pub Date : 2025-04-01 Epub Date: 2025-01-28 DOI: 10.1016/j.plefa.2025.102668

Mohammed Al Sinani , Mark Johnson , Michael Crawford , Mohammed Al Maqbali , Samir Al-Adawi

Introduction

Maternal depression during and after pregnancy is a worldwide public concern. Low omega-3 FAs levels and intake in women during pregnancy were associated with a high rate of maternal depression and poor pregnancy outcomes. The study examines the association between FAs intake and levels and prenatal depressive and anxiety symptoms among pregnant Arabic-speaking women in Oman.

Methodology

In 302 pregnant Omani women, level of depression and anxiety is assessed at the 8–12 and 24–28 weeks of pregnancy using the Arabic version of (EPDS). Seafood and the omega-3 FAs intakes of pregnant women has been quantified by using a validated (FFQ). FAs analysis of erythrocytes was carried out using the method of Folch et al.

Results

Maternal depression and anxiety symptoms (30.5 % and 26.1 %) were associated with low fish consumption and omega-3 FAs intake with depressive and anxiety symptoms (p = 0.01), Women with antenatal depression or anxiety symptoms had a lower erythrocyte concentration of arachidonic acid (20:4 n-6), (p = 0.01), total omega 6 FAs, (p = 0.03), docosahexaenoic acid (22:6 n-3) (p = 0.03), docosapentaenoic acid (22:5 n-3) (p = 0.04), eicosapentaenoic acid (20:5 n-3) (p = 0.005), total omega 3 FAs (p = 0.005), omega-3 index (p = 0.01), compared to healthy pregnant women. These findings did not change after adjusting for potential confounders.

Conclusions

Maternal omega-3 FAs exert a favourable effect on vital perinatal health outcomes. Fish and seafood intake or omega-3 FAs supplementation are highly recommended for women during pregnancy to ensure the well-being of both the mother and fetus.

孕妇孕期及产后抑郁是一个全球关注的问题。孕期妇女低omega-3脂肪酸水平和摄入量与高产妇抑郁率和不良妊娠结局有关。该研究调查了阿曼讲阿拉伯语的孕妇中FAs摄入量和水平与产前抑郁和焦虑症状之间的关系。方法对302名阿曼孕妇在怀孕8-12周和24-28周时的抑郁和焦虑水平进行评估，采用阿拉伯语版（EPDS）。孕妇的海产品和omega-3脂肪酸的摄入量已经通过使用一个有效的（FFQ）进行了量化。结果母亲抑郁和焦虑症状（30.5%和26.1%）与低鱼摄入量和omega-3脂肪酸摄入与抑郁和焦虑症状相关（p = 0.01），产前抑郁或焦虑症状的妇女红细胞花生四烯酸浓度（20:4 n-6）（p = 0.01）、总omega- 6脂肪酸（p = 0.03）、二十二碳六烯酸（22:6 n-3）（p = 0.03）较低。二十二碳五烯酸（22:5 n-3）（p = 0.04）、二十碳五烯酸（20:5 n-3）（p = 0.005）、总omega-3 FAs （p = 0.005）、omega-3指数（p = 0.01）。在调整了潜在的混杂因素后，这些发现没有改变。结论母体omega-3脂肪酸对围产期重要健康结局有有利影响。强烈建议妇女在怀孕期间摄入鱼类和海鲜或补充omega-3脂肪酸，以确保母亲和胎儿的健康。

{"title":"Depression and anxiety in the pregnant Omani population in relation to their fatty acid intake and levels","authors":"Mohammed Al Sinani , Mark Johnson , Michael Crawford , Mohammed Al Maqbali , Samir Al-Adawi","doi":"10.1016/j.plefa.2025.102668","DOIUrl":"10.1016/j.plefa.2025.102668","url":null,"abstract":"<div><h3>Introduction</h3><div>Maternal depression during and after pregnancy is a worldwide public concern. Low omega-3 FAs levels and intake in women during pregnancy were associated with a high rate of maternal depression and poor pregnancy outcomes. The study examines the association between FAs intake and levels and prenatal depressive and anxiety symptoms among pregnant Arabic-speaking women in Oman.</div></div><div><h3>Methodology</h3><div>In 302 pregnant Omani women, level of depression and anxiety is assessed at the 8–12 and 24–28 weeks of pregnancy using the Arabic version of (EPDS). Seafood and the omega-3 FAs intakes of pregnant women has been quantified by using a validated (FFQ). FAs analysis of erythrocytes was carried out using the method of Folch et al.</div></div><div><h3>Results</h3><div>Maternal depression and anxiety symptoms (30.5 % and 26.1 %) were associated with low fish consumption and omega-3 FAs intake with depressive and anxiety symptoms (<em>p</em> = 0.01), Women with antenatal depression or anxiety symptoms had a lower erythrocyte concentration of arachidonic acid (20:4 n-6), (<em>p</em> = 0.01), total omega 6 FAs, (<em>p</em> = 0.03), docosahexaenoic acid (22:6 n-3) (<em>p</em> = 0.03), docosapentaenoic acid (22:5 n-3) (<em>p</em> = 0.04), eicosapentaenoic acid (20:5 n-3) (<em>p</em> = 0.005), total omega 3 FAs (<em>p</em> = 0.005), omega-3 index (<em>p</em> = 0.01), compared to healthy pregnant women. These findings did not change after adjusting for potential confounders.</div></div><div><h3>Conclusions</h3><div>Maternal omega-3 FAs exert a favourable effect on vital perinatal health outcomes. Fish and seafood intake or omega-3 FAs supplementation are highly recommended for women during pregnancy to ensure the well-being of both the mother and fetus.</div></div>","PeriodicalId":94179,"journal":{"name":"Prostaglandins, leukotrienes, and essential fatty acids","volume":"204 ","pages":"Article 102668"},"PeriodicalIF":3.0,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143144375","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0