Prostaglandins, leukotrienes, and essential fatty acids最新文献_第3页

Predictive role of erythrocyte fatty acids in conversion to psychosis: a longitudinal study of clinical high-risk individuals 红细胞脂肪酸在精神病转化中的预测作用：一项临床高危个体的纵向研究

IF 3

Prostaglandins, leukotrienes, and essential fatty acids

Pub Date : 2025-10-01 Epub Date: 2025-07-23 DOI: 10.1016/j.plefa.2025.102698

LiHua Xu , YanYan Wei , XiaoChen Tang , ZhengHui Yi , XiaoHua Liu , HaiChun Liu , ZiXuan Wang , Tao Chen , Jin Gao , Qiang Hu , LingYun Zeng , ChunBo Li , JiJun Wang , TianHong Zhang

Introduction

Fatty acid (FA) alterations are associated in patients with psychosis. This study aimed to investigate the role of FAs in predicting the conversion to psychosis in individuals at clinical high-risk (CHR) and to distinguish CHR individuals from healthy controls (HC).

Materials and methods

A three-year longitudinal study was conducted involving 67 CHR individuals and 25 HC participants. Comprehensive erythrocyte FA profiles were obtained from gas chromatography analysis at baseline, measuring 17 different FAs. Participants were followed for three years to determine outcomes, categorizing CHR individuals into converters to psychosis (CHR-C) and non-converters (CHR-NC). We employed LASSO regression models to identify key predictors for CHR-C from CHR and to distinguish CHR from HC. Receiver operating characteristic (ROC) curve analyses were performed to evaluate the models' predictive and discriminative abilities. Significant differences in FA profiles were observed among HC, CHR-C, and CHR-NC groups.

Results

CHR-C individuals exhibited higher levels of Eicosenoic acid(p = 0.016), Linoleic acid(p = 0.009), Eicosadienoic acid(p = 0.035) and Arachidonic acid(p = 0.037) compared to CHR-NC, whereas CHR individuals showed elevated levels of Palmitoleic acid(p = 0.002), Palmitic acid(p = 0.012), Eicosapentaenoic acid(p = 0.019) and Oleic acid(p = 0.039) compared to HC. The LASSO model identified key sociodemographic and FA predictors, including age, education, and specific FAs, for distinguishing CHR from HC, demonstrating high discriminative ability with an area under the ROC curve(AUC) of 0.894. For predicting CHR-C, the model highlighted gender and specific ω-6 FAs as potential predictors, with an AUC of 0.801.

Discussion

Our findings reveal distinct FA profiles among HC, CHR-C, and CHR-NC groups and identify key predictors for psychosis conversion and CHR status. These results underscore the significance of FAs in the various stages of psychosis development.

脂肪酸（FA）的改变与精神病患者有关。本研究旨在探讨FAs在预测临床高危人群（CHR）转化为精神病中的作用，并将CHR个体与健康对照（HC）区分开来。材料与方法对67名CHR个体和25名HC参与者进行了为期3年的纵向研究。在基线气相色谱分析中获得了全面的红细胞FA谱，测量了17种不同的FA。参与者随访三年以确定结果，将CHR个体分为精神病转化者（chrc）和非转化者（chrc - nc）。我们使用LASSO回归模型来识别CHR- c和CHR的关键预测因子，并区分CHR和HC。采用受试者工作特征（ROC）曲线分析评价模型的预测和判别能力。HC组、chrc组和chrc - nc组FA谱有显著差异。结果schr - c个体的二十烯酸（p = 0.016）、亚油酸（p = 0.009）、二十碳二烯酸（p = 0.035）和花生四烯酸（p = 0.037）水平高于HC，而CHR个体的棕榈油酸（p = 0.002）、棕榈酸（p = 0.012）、二十碳五烯酸（p = 0.019）和油酸（p = 0.039）水平高于HC。LASSO模型确定了关键的社会人口学和FA预测因子，包括年龄、教育程度和特定FA，用于区分CHR和HC，显示出较高的判别能力，ROC曲线下面积（AUC）为0.894。对于预测CHR-C，该模型突出了性别和特定ω-6 FAs作为潜在的预测因子，AUC为0.801。我们的研究结果揭示了HC、chrc和chrc - nc组中不同的FA特征，并确定了精神病转化和CHR状态的关键预测因素。这些结果强调了FAs在精神病发展的各个阶段的重要性。

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引用次数: 0

Maternal blood glucose level is correlated to offspring brain fatty acid composition in a mouse model for gestational diabetes mellitus 在妊娠糖尿病小鼠模型中，母体血糖水平与子代脑脂肪酸组成相关

IF 3.2

Prostaglandins, leukotrienes, and essential fatty acids

Pub Date : 2025-10-01 Epub Date: 2025-08-15 DOI: 10.1016/j.plefa.2025.102700

Lidewij Schipper , Noela Schaap , Yixian Liu , Hongyu Li , Weiping Han , Louise Harvey

Gestational diabetes mellitus (GDM) may increase the risk of suboptimal neurocognitive development in infants. Maternal supply of omega-3 and -6 long chain polyunsaturated fatty acids (LCPUFAs), including eicosapentaeonic acid, docosahexaenoic acid and arachidonic acid, are critical for offspring brain development. To study the effects of GDM on offspring brain fatty acid composition, C57BL/6J mice were exposed to short-term high-fat diet feeding and low-dose streptozotocin treatments before pregnancy. Maternal blood glucose levels positively correlated to offspring brain omega 6:omega 3 ratio at postnatal day 2 and day 21, which appeared to be driven specifically by higher omega-6 LCPUFA levels. GDM may be associated with impaired brain fatty acid profile in offspring, and this may underpin altered neurodevelopmental outcomes after GDM pregnancies. These findings support further investigation into the therapeutic potential of postnatal dietary interventions targeting fatty acid status in infants born after GDM.

妊娠期糖尿病（GDM）可能增加婴儿神经认知发育次优的风险。母体提供omega-3和-6长链多不饱和脂肪酸（LCPUFAs），包括二十碳五烯酸、二十二碳六烯酸和花生四烯酸，对后代大脑发育至关重要。为了研究GDM对子代脑脂肪酸组成的影响，在妊娠前给C57BL/6J小鼠短期高脂饲料喂养和低剂量链脲佐菌素治疗。在出生后第2天和第21天，母亲的血糖水平与后代大脑中的omega-6:omega - 3比例呈正相关，这似乎是由更高的omega-6 LCPUFA水平特别驱动的。GDM可能与后代脑脂肪酸谱受损有关，这可能是GDM妊娠后神经发育结果改变的基础。这些发现支持进一步研究针对GDM后出生的婴儿的脂肪酸状态的产后饮食干预的治疗潜力。

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引用次数: 0

Sex and dietary ALA and DHA effects on rat heart phospholipase A2 activity mediating fatty acid release and oxylipin formation have cardiovascular implications 性别和膳食ALA和DHA对大鼠心脏磷脂酶A2活性的影响，介导脂肪酸释放和氧化脂质的形成

IF 3

Prostaglandins, leukotrienes, and essential fatty acids

Pub Date : 2025-10-01 Epub Date: 2025-06-27 DOI: 10.1016/j.plefa.2025.102697

Anne Manson , Tanja Winter , Harold M. Aukema

The ways in which diet and sex influence heart phospholipase A₂ (PLA₂) 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)PLA₂ (Varespladib) or calcium-independent (i)PLA₂ (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. sPLA₂ 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 iPLA₂. iPLA₂ activity was less selective, with activity towards all measured PUFA and oxylipins, with the primary PUFA released depending on diet. For both sPLA₂ and iPLA₂, 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 PLA₂ types in cardiovascular oxylipin biology.

饮食和性别影响心脏磷脂酶A2 （PLA2）活性的方式尚未得到充分研究，特别是对氧脂素形成的影响。因此，给雄性和雌性Sprague-Dawley大鼠喂食含有1.3% α-亚麻酸（ALA）或二十二碳六烯酸（DHA）的饲料6周，并用分泌PLA2 （Varespladib）或钙非依赖性PLA2（甲基花生四烯酰基氟膦酸盐）抑制剂孵育心脏匀浆。采用HPLC-MS/MS法测定非酯化多不饱和脂肪酸（PUFA）和氧脂类，采用3-way重复测量方差分析。sPLA2活性对DHA释放和DHA氧化脂形成具有选择性，对花生四烯酸（ARA）释放的贡献率为~ 50%，但对ARA氧化脂形成的贡献率仅为~ 30%。二十碳五烯酸（Eicosapentaenoic acid， EPA）的释放和氧化脂质的形成作用较小，但主要由iPLA2介导。iPLA2活性的选择性较低，对所有测量的PUFA和氧化脂类都有活性，主要PUFA的释放取决于饮食。对于sPLA2和iPLA2， DHA饮食对DHA及其氧化脂质的活性更高，ALA饮食对ALA和ARA及其氧化脂质的活性更高。脂肪酸和氧化脂的性别效应不同，雌性的DHA、EPA和ALA释放量较高，而雄性的DGLA和环氧合酶衍生的ARA氧化脂形成量较高。有趣的是，添加DHA后，环氧合酶ARA氧脂的性别效应减弱。这些发现为同时测量PUFA和氧化脂提供了进一步的理论依据，因为它们并不总是一致的，并为饮食和性别对心血管氧化脂生物学中PLA2类型的影响提供了新的思路。

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引用次数: 0

Fatty acid tissue composition in mice fed diets containing varying levels of Omega-3 fatty acids 喂食含有不同水平欧米伽-3脂肪酸饮食的小鼠的脂肪酸组织组成

IF 3

Prostaglandins, leukotrienes, and essential fatty acids

Pub Date : 2025-10-01 Epub Date: 2025-05-23 DOI: 10.1016/j.plefa.2025.102688

Nahed Hussein , Irina Dahms , Norman Salem Jr.

This study compares varying levels of dietary α-linolenic acid (ALA) as well as eicosapentaenoic acid (EPA) plus docosahexaenoic acid (DHA) on the fatty acid composition of multiple tissues. Two-day pregnant, C57Bl6 mice were fed through gestation and lactation with four custom made diets and the offspring were weaned to the corresponding diet: n-3 deficient (ALA, 0.07wt % of dietary fatty acids), Low ALA (0.4wt %), High ALA (5wt %), and a Low ALA enriched with DHA (2wt %) plus EPA (2wt %). The fatty acid profiles in nine tissues/organs were determined at 12 wk of age by gas chromatography. In the brain, dietary DHA+ EPA supplementation produced a slight increase in DHA but produced no effect on retina in comparison to the High ALA diet. This contrasted with liver, heart, plasma, thigh muscle where the EPA+DHA diet produced higher levels of tissue EPA and DHA compared with the ALA diets. The proportion of arachidonic acid (AA) was depressed at the DHA+ EPA intake in retina, but not brain when compared to the High ALA diet. Tissue incorporation of EPA appeared maximal for the DHA+ EPA supplementation diet, with more than a 3-fold increase in the heart when compared to the High ALA diet. The highest level of DHA was found in heart (32 %), followed by retina (27 %) in the DHA+EPA supplemented diet. These results suggest that even high levels of ALA generally cannot support the higher tissue levels of EPA or DHA found when preformed long chain n-3 PUFA are supplied in the diet.

本研究比较了饲粮中不同水平α-亚麻酸（ALA）和二十碳五烯酸（EPA）加二十二碳六烯酸（DHA）对多种组织脂肪酸组成的影响。怀孕2天的C57Bl6小鼠在妊娠期和哺乳期饲喂4种定制的日粮，断奶后分别饲喂n-3缺乏（ALA， 0.07wt %的日粮脂肪酸）、低ALA （0.4wt %）、高ALA （5wt %）和富含DHA （2wt %）和EPA （2wt %）的低ALA。12周龄时用气相色谱法测定9个组织/器官的脂肪酸谱。在大脑中，与高ALA饮食相比，饮食中DHA+ EPA的补充会产生DHA的轻微增加，但对视网膜没有影响。这与肝脏、心脏、血浆和大腿肌肉形成对比，EPA+DHA饮食比ALA饮食产生了更高水平的组织EPA和DHA。与高ALA饮食相比，DHA+ EPA摄入降低了视网膜中花生四烯酸（AA）的比例，但大脑中没有。在DHA+ EPA补充饮食中，EPA的组织掺入量最大，与高ALA饮食相比，心脏的EPA掺入量增加了3倍以上。在DHA+EPA补充饮食中，DHA含量最高的部位是心脏（32%），其次是视网膜（27%）。这些结果表明，即使是高水平的ALA通常也不能支持在饮食中提供预形成的长链n-3 PUFA时所发现的较高组织水平的EPA或DHA。

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引用次数: 0

The influence of biological sex on skeletal muscle phospholipid membrane composition in response to omega n-3 polyunsaturated fatty acid supplementation and washout in humans 生物性别对骨骼肌磷脂膜组成的影响，以响应omega - n-3多不饱和脂肪酸的补充和冲洗

IF 3

Prostaglandins, leukotrienes, and essential fatty acids

Pub Date : 2025-10-01 Epub Date: 2025-06-27 DOI: 10.1016/j.plefa.2025.102696

Callum J. Pufahl , Sydney E. Smart , Justin Bureau , Brendan Ross , Craig A. Simpson , Adam H. Metherel , James R. Dick , Chris McGlory

Omega n-3 polyunsaturated fatty acid (n-3 PUFA) intake is associated with reduced inflammation, protection against cardiovascular disease, and improved cognitive function. There is also evidence that n-3 PUFA intake impacts skeletal muscle, potentially with greater effects in females than males. Sex-specific responses to n-3 PUFA intake may be linked to the incorporation of eicosapentaenoic acid (EPA; 20:5n-3) and docosahexaenoic acid (DHA; 22:6n-3) into skeletal muscle phospholipid membranes. However, no study has characterized the effect of biological sex on human skeletal muscle phospholipid composition in response to EPA+DHA supplementation, and washout of EPA and DHA from skeletal muscle phospholipids following the cessation of supplementation. In a repeated measures design, 15 females and 14 males consumed 5 g/d of EPA+DHA (3.75 g EPA; 1.25 g DHA) for 8 weeks followed by 14 weeks of washout. Skeletal muscle biopsies and venous blood samples were obtained at weeks 0 (baseline), 6, 8, 16, 20, and 22. Females displayed greater skeletal muscle EPA phospholipid composition (p= 0.035) at 6 weeks of supplementation, higher erythrocyte EPA phospholipid composition (p= 0.034), and whole plasma DHA composition (p= 0.033) compared to males. At 14 weeks of washout, skeletal muscle and erythrocyte EPA phospholipid composition (p< 0.001 and p= 0.005) remained elevated above baseline, whereas whole plasma EPA composition (p= 0.381) was not different from baseline. We demonstrate that 5 g/d EPA+DHA supplementation influences human fatty acid composition in a manner that is both sex- and tissue-dependant.

摄入Omega n-3多不饱和脂肪酸（n-3 PUFA）与减少炎症、预防心血管疾病和改善认知功能有关。还有证据表明，摄入n-3多聚脂肪酸会影响骨骼肌，对女性的影响可能比男性更大。对n-3 PUFA摄入的性别特异性反应可能与二十碳五烯酸(EPA；20:5n-3)和二十二碳六烯酸(DHA；22:6n-3)进入骨骼肌磷脂膜。然而，没有研究表明生物性别对EPA+DHA补充后骨骼肌磷脂组成的影响，以及停止补充后骨骼肌磷脂中EPA和DHA的流失。在重复测量设计中，15名女性和14名男性摄入5 g/d的EPA+DHA (3.75 g EPA；1.25 g DHA) 8周，然后是14周的洗脱期。在第0周（基线）、第6周、第8周、第16周、第20周和第22周采集骨骼肌活检和静脉血样本。在补充6周后，女性的骨骼肌EPA磷脂组成（p= 0.035）、红细胞EPA磷脂组成（p= 0.034）和全血浆DHA组成（p= 0.033）均高于男性。在洗脱期第14周，骨骼肌和红细胞EPA磷脂组成(p<；0.001和p= 0.005)仍然高于基线，而全血浆EPA组成（p= 0.381）与基线没有差异。我们证明，5 g/d的EPA+DHA补充剂影响人体脂肪酸组成的方式是性别和组织依赖的。

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引用次数: 0

Association of birth outcomes with maternal and infant FADS1 rs174547 genotypes in Japanese participants 日本参与者出生结局与母婴FADS1 rs174547基因型的关系

IF 3

Prostaglandins, leukotrienes, and essential fatty acids

Pub Date : 2025-10-01 Epub Date: 2025-04-14 DOI: 10.1016/j.plefa.2025.102683

Reiko Nita , Terue Kawabata , Yasuo Kagawa , Kumiko Shoji , Kazuhiro Nakayama , Sadahiko Iwamoto , Yoshiko Yanagisawa , Fumiko Kimura , Teruo Miyazawa , Nozomi Tatsuta , Takahiro Arima , Nobuo Yaegashi , Kunihiko Nakai

N-3 long-chain polyunsaturated fatty acids (n-3LCPUFAs) are crucial for child growth and development particularly for fetal growth in utero and brain development and function. This study examined the relationship between birth outcomes and FADS1 rs174547 genotypes in Japanese mothers and infants. The study included 406 mothers and 373 infants, i.e., 373 infant–mother pairs, from a supplementary survey of the Japan Environment and Children's Study. Multiple regression analysis revealed that infants with the CC genotype had significantly smaller head circumference at birth compared to those with the TT genotype. Moreover, an interaction between infant genotype and cord blood docosahexaenoic acid (DHA; 22:6n-3) composition affected head circumference at birth. The findings suggest that maternal and infant FADS1 genotypes may influence fetal growth. Furthermore, in FADS1 genotype-stratified multiple regression analysis, infants with maternal and infant CC genotypes exhibited a significant positive association between head circumference at birth and maternal erythrocyte DHA/α-linolenic acid (ALA; 18:3n-3) ratio or fish intake. We highlighted lower metabolic efficiency for endogenous long-chain polyunsaturated fatty acids synthesis in infant–mother pairs homozygous for the minor C allele of FADS1 rs174547. In conclusion, for mothers and infants with this genetic background, maternal fish intake during pregnancy may be potentially important for fetal growth and development.

N-3长链多不饱和脂肪酸（n-3LCPUFAs）对儿童的生长发育至关重要，特别是对胎儿在子宫内的生长和大脑的发育和功能。本研究探讨了日本母婴FADS1 rs174547基因型与出生结局的关系。该研究包括406名母亲和373名婴儿，即373对婴儿-母亲，来自日本环境与儿童研究的补充调查。多元回归分析显示，CC基因型婴儿出生时头围明显小于TT基因型婴儿。此外，婴儿基因型与脐带血二十二碳六烯酸(DHA；[22:6]成分影响出生时的头围。研究结果表明，母婴FADS1基因型可能影响胎儿生长。此外，在FADS1基因型分层多元回归分析中，母亲和婴儿CC基因型的婴儿出生时头围与母亲红细胞DHA/α-亚麻酸(ALA；18:3n-3)比例或鱼的摄入量。我们强调了FADS1 rs174547小等位基因C纯合的母婴对内源性长链多不饱和脂肪酸合成的代谢效率较低。总之，对于具有这种遗传背景的母亲和婴儿来说，母亲在怀孕期间摄入鱼类可能对胎儿的生长发育有潜在的重要影响。

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引用次数: 0

Linoleic acid promotes mammary tumor growth and metastasis to brain and lung in female Balb/cJ mice 亚油酸促进Balb/cJ雌性小鼠乳腺肿瘤生长及脑和肺转移

IF 3

Prostaglandins, leukotrienes, and essential fatty acids

Pub Date : 2025-10-01 Epub Date: 2025-05-29 DOI: 10.1016/j.plefa.2025.102687

Maria Sanchez-Juarez , Monica Vizcarra-Soto , Rocio Castillo-Sanchez , Pablo Torres-Alamilla , Pedro Cortes-Reynosa , Gustavo Acosta-Altamirano , Monica Sierra-Martinez , Eduardo Perez Salazar

Breast cancer is the leading cause of mortality among women worldwide. The largest prevalence of breast cancer is present in high-income nations, but the incidence in low- to middle-income countries has risen in recent years, which is the consequence of various causes, such as dietary habits. Dietary fat intake is a factor associated with the risk of developing breast cancer, and a moderate positive association between n-6 fatty acids and breast cancer risk has been described. Linoleic acid (LA) is an omega-6 polyunsaturated fatty acid (PUFA), which represents an essential PUFA and the major fatty acid consumed in occidental diets. It has been demonstrated that LA promotes cellular processes involved with invasion/metastasis in MDA-MB-231 breast cancer cells. In this study, we demonstrate that LA induces migration via FFAR1 and FFAR4, invasion and secretion of matrix metalloproteinase (MMP)-2 and MMP-9 in 4T1 triple negative breast cancer cells. In addition, 4T1 cells treated with 60 µM LA for 7 days and then inoculated in Balb/cJ mice induces an increase in the weight and volume of mammary tumors, and an increase in the metastasis to brain and liver compared with Balb/cJ mice inoculated with untreated 4T1 cells. In conclusion, LA induces cellular processes involved with invasion/metastasis and an increase in the growth of mammary tumors and metastasis in a murine model of breast cancer using Balb/cJ mice and 4T1 cells.

乳腺癌是全世界妇女死亡的主要原因。乳腺癌发病率最高的是高收入国家，但近年来中低收入国家的发病率有所上升，这是多种原因造成的，比如饮食习惯。饮食中脂肪的摄入是与患乳腺癌风险相关的一个因素，n-6脂肪酸与患乳腺癌风险之间存在适度的正相关关系。亚油酸（LA）是一种omega-6多不饱和脂肪酸（PUFA），是一种必需的多不饱和脂肪酸，也是西方人饮食中消耗的主要脂肪酸。已经证明LA促进了MDA-MB-231乳腺癌细胞侵袭/转移的细胞过程。在这项研究中，我们证明了LA通过FFAR1和FFAR4诱导4T1三阴性乳腺癌细胞的迁移、基质金属蛋白酶(MMP)-2和MMP-9的侵袭和分泌。此外，与未接种4T1细胞的Balb/cJ小鼠相比，4T1细胞经60µM LA处理7天后接种于Balb/cJ小鼠，可诱导乳腺肿瘤的重量和体积增加，脑和肝脏转移增加。综上所述，在Balb/cJ小鼠和4T1细胞的小鼠乳腺癌模型中，LA诱导了参与侵袭/转移的细胞过程，并增加了乳腺肿瘤的生长和转移。

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引用次数: 0

Fatty acid synthase global inducible knockout does not alter brain fatty acid concentrations but attenuates cholesterol synthesis in the adult mouse 脂肪酸合酶的诱导敲除不会改变脑脂肪酸浓度，但会减弱成年小鼠的胆固醇合成

IF 3

Prostaglandins, leukotrienes, and essential fatty acids

Pub Date : 2025-07-01 Epub Date: 2025-03-31 DOI: 10.1016/j.plefa.2025.102679

Drew R. Seeger, Peddanna Kotha, Svetlana A. Golovko, Eric J. Murphy, Mikhail Y. Golovko

Fatty acid (FA) de novo synthesis, also called de novo lipogenesis (DNL), has a central role in peripheral energy storage and provides structural components for lipid membranes. However, less is known regarding its contribution to brain FA homeostasis. DNL is catalyzed by fatty acid synthase (FAS), which is a multifunctional enzyme expressed in all mammalian tissues. In the present study, we addressed, for the first time, the effect of FAS gene global conditional inducible knockout (Fasn KO) on the adult brain FA concentrations and lipid metabolism. We achieved a 67 % reduction in the brain FAS protein levels, with a significant reduction in total FA synthesis measured by ³H₂O incorporation into FA, which was lethal 10 days after gene recombination induction. However, the concentrations of all 44 FA molecular species assayed by LC-MS were unchanged in the brain. We also did not detect changes in the major proteins involved in FA synthesis regulation and remodeling, including peroxisome proliferator-activated receptor α (PPARα), PPARδ, FA desaturase-1, -2, and -3, and Stearoyl-CoA desaturase 1 but did observe a decrease in PPARɣ levels. In addition, brain cholesterol synthesis was significantly reduced in the Fasn KO brains. These data indicate that DNL is not required to maintain measured FA concentrations in the brain and that dietary FA and liver-derived pools might compensate for decreased brain DNL within the duration of the study. However, our data indicate a possible role of FAS in PPARɣ regulation and cholesterol metabolism in the adult brain.

脂肪酸（FA）从头合成，也称为从头脂肪生成（DNL），在外周能量储存中起核心作用，并为脂质膜提供结构成分。然而，它对大脑FA稳态的贡献知之甚少。脂肪酸合成酶（fatty acid synthase， FAS）是一种在哺乳动物所有组织中表达的多功能酶。在本研究中，我们首次讨论了FAS基因全局条件诱导敲除（Fasn KO）对成人脑FA浓度和脂质代谢的影响。我们发现大脑FAS蛋白水平降低了67%，通过将3H2O掺入FA测量的总FA合成显著降低，这在基因重组诱导后10天是致命的。然而，LC-MS检测的所有44种FA分子种在脑内的浓度不变。我们也没有检测到参与FA合成调节和重塑的主要蛋白质的变化，包括过氧化物酶体增殖物激活受体α (PPARα), PPARδ， FA去饱和酶-1，-2和-3以及硬脂酰辅酶a去饱和酶1，但确实观察到PPARα水平下降。此外，Fasn KO脑内胆固醇合成显著减少。这些数据表明，DNL不需要维持大脑中测量的FA浓度，并且饮食FA和肝脏来源的池可能在研究期间补偿大脑中DNL的减少。然而，我们的数据表明FAS在成人大脑中PPAR α调节和胆固醇代谢中的可能作用。

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引用次数: 0

Fatty acid metabolism in the placentae of gestational diabetes mellitus 妊娠期糖尿病胎盘脂肪酸代谢的研究

IF 3

Prostaglandins, leukotrienes, and essential fatty acids

Pub Date : 2025-07-01 Epub Date: 2025-04-05 DOI: 10.1016/j.plefa.2025.102682

Nikita Joshi, Sadhana Joshi

The prevalence of gestational diabetes mellitus (GDM), a metabolic complication during pregnancy is increasing rapidly. It exerts various short and long term effects on the mother and the child. Nonetheless, the mechanisms underlying the pathophysiology of GDM are still not clear. Placenta is a key ‘programming’ agent and any impairment in placental structure and function may hamper the fetal growth and development. Omega-3 and omega-6 fatty acids are key nutrients involved in placental and fetal development. The fatty acids transport from maternal circulation towards the fetus depends on the fatty acid status of the mother, fatty acid metabolism of the placenta and placental transport of fatty acids. Alteration in any of these could influence the fatty acids transport towards the fetus thereby affecting the fetal brain development and leading to impairment in cognitive function in the off-spring. We propose a role for placental fatty acid metabolism in influencing fetal growth and development which in turn can have an impact on cognitive development of the offspring born to GDM women.

妊娠糖尿病（GDM）是一种孕期代谢并发症，其发病率正在迅速上升。它对母婴产生各种短期和长期影响。然而，GDM 的病理生理学机制仍不清楚。胎盘是 "编程 "的关键因素，胎盘结构和功能的任何损伤都可能阻碍胎儿的生长发育。奥米加 3 和奥米加 6 脂肪酸是胎盘和胎儿发育的关键营养素。脂肪酸从母体循环向胎儿的运输取决于母体的脂肪酸状况、胎盘的脂肪酸代谢和胎盘的脂肪酸运输。其中任何一个环节的改变都可能影响脂肪酸向胎儿的运输，从而影响胎儿的大脑发育，导致后代认知功能受损。我们提出了胎盘脂肪酸代谢在影响胎儿生长发育中的作用，而胎儿的生长发育反过来又会影响 GDM 妇女所生后代的认知发展。

引用次数: 0

Plasma oxylipins in children with sickle cell disease: Associations with biomarkers of inflammation and endothelial activation 镰状细胞病儿童血浆氧脂素：与炎症和内皮细胞激活的生物标志物的关联

IF 3

Prostaglandins, leukotrienes, and essential fatty acids

Pub Date : 2025-07-01 Epub Date: 2025-02-24 DOI: 10.1016/j.plefa.2025.102670

BN Yamaja Setty , Krishna Rao Maddipati , Scott W Keith , Ayako Shimada , Pari Sheerer , Robin E Miller

Oxylipins are polyunsaturated fatty acid (PUFA)-derived inflammatory mediators, and include both pro-inflammatory (prostaglandins, thromboxane, leukotrienes), and pro-resolving (lipoxins, E-resolvins, D-resolvins, protectins, maresins) molecules. Sickle cell disease (SCD) is an inflammatory pathology. We profiled plasma oxylipins in SCD (n = 45) and control children (n = 24), and evaluated their associations with inflammatory biomarkers, and SCD clinical history. We demonstrated the presence of PGE2, TxB2, RvE2, RvD1, AT-RvD3, and numerous monohydroxy-PUFAs in both SCD and control plasma. Levels of TxB2, RvD1, 12-HETE, 5-HEPE, and 7-HDoHE were significantly increased in SCD. 12-HETE and 5-HEPE correlated positively with IL-6 and IL-1β, respectively, while 15-HETE negatively associated with soluble-ICAM-1. 7-HDoHE levels were significantly lower in children with a history of VOC and ACS compared to those without any clinical complications. Since RvD1 is a pro-resolving mediator, the observed increase in RvD1 in SCD may reflect a host mechanism attempting to mitigate disease-associated chronic inflammation by promoting resolution of inflammation.

氧脂素是多不饱和脂肪酸（PUFA）衍生的炎症介质，包括促炎（前列腺素、血栓素、白三烯）和促溶解（脂毒素、e -溶解蛋白、d -溶解蛋白、保护蛋白、蛋白）分子。镰状细胞病（SCD）是一种炎性病理。我们分析了45名SCD儿童和24名对照儿童的血浆氧脂素，并评估了它们与炎症生物标志物和SCD临床病史的关系。我们证实在SCD和对照血浆中存在PGE2、TxB2、RvE2、RvD1、AT-RvD3和许多单羟基pufas。SCD患者TxB2、RvD1、12-HETE、5-HEPE、7-HDoHE水平显著升高。12-HETE和5-HEPE分别与IL-6和IL-1β呈正相关，而15-HETE与可溶性icam -1呈负相关。与没有任何临床并发症的儿童相比，有VOC和ACS病史的儿童的7-HDoHE水平明显较低。由于RvD1是一种促溶解介质，因此在SCD中观察到的RvD1的增加可能反映了一种宿主机制，它试图通过促进炎症的溶解来减轻疾病相关的慢性炎症。

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