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Excess maternal vitamin B12 supplementation increases oxidative stress and differentially influences fatty acids profile in a rat model 在大鼠模型中,过量的母体维生素B12补充会增加氧化应激并对脂肪酸谱产生不同的影响。
IF 3.2 Pub Date : 2025-12-01 Epub Date: 2025-11-06 DOI: 10.1016/j.plefa.2025.102715
Sunaina Chhetri, Nisha Kemse, Juhi Nema, Sadhana Joshi
Vitamin B12 status during pregnancy is an important determinant for non-communicable disease risk in later life. Vitamin B12 and fatty acid are interlinked in one carbon cycle. The effect of vitamin B12 deficiency on adverse pregnancy outcomes and fatty acid status is well known. However, the effects of excess vitamin B12 supplementation during pregnancy are less explored. This study investigates the influence of prenatal excess vitamin B12 supplementation on pregnancy outcome, fatty acids, oxidative stress, inflammation and cardiometabolic variables in Wistar rats. Female rats were divided (pre-pregnancy to pregnancy) into 3 groups as control (0.375 μg/day of vitamin B12), intermediate group (1.5 μg/day) and excess group (120 μg/day). At d20 of gestation, dams were sacrificed to collect blood and placenta for biochemical estimation. We found higher plasma vitamin B12 levels in the intermediate group and excess group (p < 0.01 for both), while folate and homocysteine levels were found to be similar across groups. The pregnancy outcome was similar between groups. We found higher erythrocyte saturated fatty acids, lower omega-6 fatty acids, omega-6/omega-3 fatty acid ratio, and Δ5 desaturase index (p < 0.05 for all) in excess group in comparison with the control group. In comparison with the control group, higher placental Δ6 desaturase index (p < 0.05) and plasma malondialdehyde levels were found (p < 0.01) in excess group. Our study demonstrates that supplementation of excess maternal vitamin B12 during pregnancy leads to increased oxidative stress and differentially influences various fatty acid levels.
怀孕期间维生素B12状况是晚年罹患非传染性疾病风险的一个重要决定因素。维生素B12和脂肪酸在一个碳循环中相互联系。维生素B12缺乏对不良妊娠结局和脂肪酸状态的影响是众所周知的。然而,怀孕期间过量补充维生素B12的影响却很少被探索。本研究探讨了产前过量补充维生素B12对Wistar大鼠妊娠结局、脂肪酸、氧化应激、炎症和心脏代谢指标的影响。将雌性大鼠(孕前至妊娠)分为对照组(0.375 μg/d)、中间组(1.5 μg/d)和过量组(120 μg/d)。在妊娠第20 d时处死母鼠采集血液和胎盘进行生化评估。我们发现,中间组和过量组的血浆维生素B12水平较高(p < 0.01),而叶酸和同型半胱氨酸水平在各组之间相似。两组间妊娠结局相似。结果发现,与对照组相比,过量组红细胞饱和脂肪酸升高,omega-6脂肪酸、omega-6/omega-3脂肪酸比值和Δ5去饱和酶指数均降低(p < 0.05)。过量组胎盘Δ6去饱和酶指数(p < 0.05)和血浆丙二醛水平均高于对照组(p < 0.01)。我们的研究表明,在怀孕期间补充过量的维生素B12会导致氧化应激增加,并对各种脂肪酸水平产生不同的影响。
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引用次数: 0
Quantifying the differential relationship between red blood cell docosahexaenoic acid and cognition based on APOE-e4 carriership in multiple cohorts: illustration of an emerging statistical approach 基于APOE-e4携带者在多个队列中量化红细胞二十二碳六烯酸与认知之间的差异关系:一种新兴统计方法的说明
IF 3.2 Pub Date : 2025-12-01 Epub Date: 2025-10-22 DOI: 10.1016/j.plefa.2025.102713
Nathan A. Ryder , Jason Westra , Aleix Sala-Vila , Jack Wolf , William S. Harris , Nathan L. Tintle
Evidence is mounting that red blood cell membrane levels of docosahexaeonic acid (DHA) are directly associated with improved cognitive performance, with emerging questions about whether this relationship may be stronger in some individuals vs. others, especially those at high genetic risk of cognitive impairment via the APOLIPOPROTEIN-E (APOE) ε4 allele. We investigated this relationship in n = 2158 participants without dementia from four separate cohorts (Offspring, Gen3, Omni I and Omni II) of the multi-cohort Framingham Heart Study, aged 50 to 70 years old. To demonstrate an emerging alternative of improved data sharing, we conducted the analysis using only cohort-level, summary data which is non-individually identifiable and easily shareable. We detected a statistically significant interaction between APOE-ε4 status and DHA in multivariable models adjusting for relevant demographic and medical history covariates and predicting cognitive impairment (p = 0.039). Stratified adjusted model results detected a stronger inverse association between cognitive impairment and DHA for APOE-ε4 carriers (-0.13; 95 % CI: (-0.20, -0.06) minutes per 1 % increase in DHA), as compared to non-carriers (-0.06; 95 % CI: (-0.11, -0.02)), though both were statistically significant (p < 0.05). We also analyzed the data using two, standard, widely used statistical approaches (1) Individual level data analysis (identical results) and (2) standard meta-analysis (slightly weaker evidence of interaction; p = 0.047). Our analysis demonstrates not only the putative importance of DHA on cognition, especially among APOE-ε4 carriers, but the potential for an emerging class of data-sharing methods to accelerate the future pace of cross-cohort analyses by not requiring access to individual-level data.
越来越多的证据表明,红细胞膜二十二碳六烯酸(DHA)水平与认知能力的提高直接相关,但这种关系是否在某些个体中比在其他人中更强,特别是那些通过载脂蛋白e (APOE) ε4等位基因具有认知障碍高遗传风险的个体中,这一问题正在出现。我们在多队列Framingham心脏研究的4个独立队列(Offspring, Gen3, Omni I和Omni II)中n = 2158名无痴呆的参与者中调查了这种关系,这些参与者年龄在50至70岁之间。为了展示一种改进数据共享的新兴替代方案,我们仅使用非个人可识别且易于共享的队列水平汇总数据进行了分析。我们发现APOE-ε4状态与DHA在多变量模型中具有统计学意义的交互作用,调整了相关的人口统计学和病史协变量,并预测认知障碍(p = 0.039)。分层调整模型结果发现,APOE-ε4携带者的认知障碍与DHA之间存在更强的负相关(-0.13;95% CI:(-0.20, -0.06)分钟/ DHA增加1%),而非携带者(-0.06;95% CI:(-0.11, -0.02)),尽管两者均具有统计学意义(p < 0.05)。我们还使用两种标准的、广泛使用的统计方法分析数据(1)个体水平数据分析(相同的结果)和(2)标准荟萃分析(相互作用的证据略弱;p = 0.047)。我们的分析不仅证明了DHA对认知的重要性,特别是在APOE-ε4携带者中,而且表明了一种新兴的数据共享方法的潜力,这种方法可以通过不需要访问个人水平的数据来加快跨队列分析的未来步伐。
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引用次数: 0
Dietary and erythrocyte PUFAs in vegan, lacto-ovo vegetarian, pesco-vegetarian, and non-vegetarian participants of the Adventist Health Study-2 复临健康研究的素食者、乳蛋素食者、鱼素食者和非素食者的饮食和红细胞PUFAs 2
IF 3.2 Pub Date : 2025-12-01 Epub Date: 2025-10-02 DOI: 10.1016/j.plefa.2025.102709
William Harris , Roman Pawlak , Nathan Ryder , Fayth Miles , Gary Fraser

Background

Data on EPA and DHA fatty acids in vegans (VGN) and vegetarians (LOV) are scarce. Also, the extent to which red blood cell (RBC) levels of these fatty acids (FAs) vary by dietary pattern and are correlated with dietary EPA+DHA intake is less well-known.

Objectives

The primary objective of this study was to compare RBC EPA and DHA content [i.e., the omega-3 index (O3I)] VGN, LOV, pesco-vegetarians (PV), and non-vegetarians (NV) in the Adventist Health Study II (AHS2). The secondary objective was to determine the extent to which the dietary intake of these PUFAs correlated with RBC levels.

Methods

Participants (N = 300, 75 per diet group) were randomly selected from AHS2 cohort. After removing individuals reporting fish oil supplement use, 241 remained for analysis. Dietary data were collected via a validated questionnaire. RBCs were analyzed for FA composition by gas chromatography.

Results

Mean O3I (±SD) O3I values across diet groups for VGNs, LOVs, PVs and NVs was 3.7 ± 1.1, 3.9 ± 1.3, 5.7 ± 2.1, and 5.0 ± 1.3, respectively, and EPA+DHA intakes (mg/d) were 10 ± 40, 18 ± 54, 158 ± 279, and 117 ± 91, respectively. EPA+DHA intake correlated strongly with the O3I (r = 0.67, p < 0.001). The dietary ratio of linoleic acid to alpha-linoleic acid was unrelated to the O3I, and the linoleic acid intake was not associated with RBC arachidonic acid levels.

Conclusions

VGNs and LOVs had O3I levels (and EPA+DHA intakes) well below recommended targets. For these groups, the most reasonable way to raise these levels is to consume algae-derived EPA+DHA supplements.
关于纯素食者(VGN)和素食者(LOV)中EPA和DHA脂肪酸的数据很少。此外,这些脂肪酸(FAs)的红细胞(RBC)水平在多大程度上随饮食模式而变化,以及与饮食中EPA+DHA摄入量的关系,目前还不太清楚。本研究的主要目的是比较基督复安息日健康研究II (AHS2)中红细胞EPA和DHA含量[即ω -3指数(O3I)] VGN, LOV,鱼素者(PV)和非素食者(NV)。次要目的是确定这些PUFAs的饮食摄入量与RBC水平的相关性。方法从AHS2队列中随机抽取受试者300例,每个饮食组75例。除去报告服用鱼油补充剂的个人后,仍有241人有待分析。饮食数据通过一份有效的问卷收集。用气相色谱法分析红细胞FA组成。结果各组vgn、LOVs、pv和NVs的平均O3I(±SD)值分别为3.7±1.1、3.9±1.3、5.7±2.1和5.0±1.3,EPA+DHA摄入量(mg/d)分别为10±40、18±54、158±279和117±91。EPA+DHA摄入量与O3I密切相关(r = 0.67, p < 0.001)。饲料中亚油酸与α -亚油酸的比值与O3I无关,亚油酸摄入量与红细胞花生四烯酸水平无关。结论svgns和LOVs的O3I水平(以及EPA+DHA摄入量)远低于推荐目标。对于这些人群来说,提高这些水平最合理的方法是食用藻类衍生的EPA+DHA补充剂。
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引用次数: 0
Associations between fatty acids providing support for n-3 and n-6 pathways are strongest in pregnant Indian vegetarians compared with pregnant Australian omnivores 提供n-3和n-6通路支持的脂肪酸在怀孕的印度素食者中比在怀孕的澳大利亚杂食动物中最强
IF 3.2 Pub Date : 2025-12-01 Epub Date: 2025-10-25 DOI: 10.1016/j.plefa.2025.102714
Michael Mugford , Bridget M Arman , Kishore Kumar , Rohini S Kaluve , Dang Xuan Anh Tran , Karen Best , Lisa N Yelland , Maria Makrides , Robert A Gibson
Exclusion of meat and fish from the diet can lead to low levels of omega-3 (n-3) long chain polyunsaturated fatty acids (LCPUFAs), leaving the body reliant on dietary intake of n-3 α-linolenic acid (ALA) for endogenous conversion. This study compared dried blood spot fatty acid profiles from a large cohort of pregnant Indian women in Bengaluru, Karnataka, with self-reported vegetarian (n = 332) or omnivorous (n = 691) diets in the first trimester, to those of pregnant Australian women (n = 454) at a similar gestational age. Indian vegetarians and omnivores showed similar fatty acid profiles in dried blood spots but both had markedly lower n-3 fatty acids (mean total n-3 values: Indian 2.01% and 2.36% of total fatty acids respectively; 4.75% in Australian) with ALA, eicosapentaenoic acid, docosapentaenoic acid, and docosahexaenoic acid all less than half the Australian values. Both Indian groups also had lower arachidonic acid levels (mean 7.65% and 7.91% respectively, vs 8.50% in Australian omnivores), and higher linoleic acid levels (mean 22.53% and 22.41% respectively, vs 19.96% in Australian omnivores) compared with the Australian participants. In general, the relationships between n-3 fatty acids were stronger in Indian vegetarians than Indian omnivores, and weakest in Australian omnivores. These findings suggest that regardless of diet, Indian women in early pregnancy have lower n-3 LCPUFA status than Australian pregnant women. Our data are consistent with the idea that increasing intake of n-3 ALA-rich oils and reducing n-6 linoleic acid-rich oils in the diet of Indian women could be an efficient way of increasing their n-3 LCPUFA status.

Clinical trial registrations

ORIP, Australian New Zealand Clinical Trials Registry number, ACTRN12613001142729; BORN, Clinical Trials Registry-India CTRI/2020/08/027146.
从饮食中排除肉类和鱼类会导致omega-3 (n-3)长链多不饱和脂肪酸(LCPUFAs)水平降低,使身体依赖于饮食摄入n-3 α-亚麻酸(ALA)进行内源性转化。这项研究比较了来自卡纳塔克邦班加罗尔的一大批印度孕妇的干血斑脂肪酸谱,这些孕妇在妊娠早期自称为素食(n = 332)或杂食性(n = 691),而澳大利亚孕妇(n = 454)在相似的胎龄。印度素食者和杂食动物在干血斑中表现出相似的脂肪酸分布,但两者的n-3脂肪酸含量都明显较低(平均总n-3值:印度分别占总脂肪酸的2.01%和2.36%,澳大利亚占4.75%),ALA、二十碳五烯酸、二十二碳五烯酸和二十二碳六烯酸均不到澳大利亚的一半。与澳大利亚参与者相比,两组印度人的花生四烯酸水平也较低(平均分别为7.65%和7.91%,而澳大利亚杂食动物为8.50%),亚油酸水平较高(平均分别为22.53%和22.41%,而澳大利亚杂食动物为19.96%)。总的来说,印度素食者的n-3脂肪酸之间的关系强于印度杂食者,而澳大利亚杂食者的n-3脂肪酸之间的关系最弱。这些发现表明,无论饮食如何,怀孕早期的印度妇女的n-3 LCPUFA水平低于澳大利亚孕妇。我们的数据与增加印度妇女饮食中富含n-3 ala的油的摄入和减少n-6亚油酸的油的摄入可能是提高她们n-3 LCPUFA状态的有效方法一致。临床试验注册sorip,澳大利亚新西兰临床试验注册号,ACTRN12613001142729;BORN, Clinical Trials Registry-India CTRI/2020/08/027146。
{"title":"Associations between fatty acids providing support for n-3 and n-6 pathways are strongest in pregnant Indian vegetarians compared with pregnant Australian omnivores","authors":"Michael Mugford ,&nbsp;Bridget M Arman ,&nbsp;Kishore Kumar ,&nbsp;Rohini S Kaluve ,&nbsp;Dang Xuan Anh Tran ,&nbsp;Karen Best ,&nbsp;Lisa N Yelland ,&nbsp;Maria Makrides ,&nbsp;Robert A Gibson","doi":"10.1016/j.plefa.2025.102714","DOIUrl":"10.1016/j.plefa.2025.102714","url":null,"abstract":"<div><div>Exclusion of meat and fish from the diet can lead to low levels of omega-3 (n-3) long chain polyunsaturated fatty acids (LCPUFAs), leaving the body reliant on dietary intake of n-3 α-linolenic acid (ALA) for endogenous conversion. This study compared dried blood spot fatty acid profiles from a large cohort of pregnant Indian women in Bengaluru, Karnataka, with self-reported vegetarian (<em>n</em> = 332) or omnivorous (<em>n</em> = 691) diets in the first trimester, to those of pregnant Australian women (<em>n</em> = 454) at a similar gestational age. Indian vegetarians and omnivores showed similar fatty acid profiles in dried blood spots but both had markedly lower n-3 fatty acids (mean total n-3 values: Indian 2.01% and 2.36% of total fatty acids respectively; 4.75% in Australian) with ALA, eicosapentaenoic acid, docosapentaenoic acid, and docosahexaenoic acid all less than half the Australian values. Both Indian groups also had lower arachidonic acid levels (mean 7.65% and 7.91% respectively, vs 8.50% in Australian omnivores), and higher linoleic acid levels (mean 22.53% and 22.41% respectively, vs 19.96% in Australian omnivores) compared with the Australian participants. In general, the relationships between n-3 fatty acids were stronger in Indian vegetarians than Indian omnivores, and weakest in Australian omnivores. These findings suggest that regardless of diet, Indian women in early pregnancy have lower n-3 LCPUFA status than Australian pregnant women. Our data are consistent with the idea that increasing intake of n-3 ALA-rich oils and reducing n-6 linoleic acid-rich oils in the diet of Indian women could be an efficient way of increasing their n-3 LCPUFA status.</div></div><div><h3>Clinical trial registrations</h3><div>ORIP, Australian New Zealand Clinical Trials Registry number, ACTRN12613001142729; BORN, Clinical Trials Registry-India CTRI/2020/08/027146.</div></div>","PeriodicalId":94179,"journal":{"name":"Prostaglandins, leukotrienes, and essential fatty acids","volume":"207 ","pages":"Article 102714"},"PeriodicalIF":3.2,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145571809","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
The association between n-6 polyunsaturated fatty acid intakes and attention deficit hyperactivity disorder in US children and adolescents: A cross-sectional study from NHANES 美国儿童和青少年n-6多不饱和脂肪酸摄入与注意缺陷多动障碍之间的关系:来自NHANES的横断面研究
IF 3.2 Pub Date : 2025-12-01 Epub Date: 2025-11-15 DOI: 10.1016/j.plefa.2025.102716
Lijin Wang , Qin Wang , Ling Li

Objective

This study aims to evaluate the relationship between dietary n-6 polyunsaturated fatty acids (PUFAs) intake and attention deficit hyperactivity disorder (ADHD) among US children and adolescents based on National Health and Nutrition Examination Survey (NHANES) data.

Methods

We conducted a cross-sectional analysis of 6077 children and adolescents using data from NHANES conducted between 2013 and 2020. Multivariate logistic regression models were employed to assess the association between dietary n-6 PUFAs and ADHD. To further examine linearity and explore the shape of the dose-response relationship, restricted cubic splines were utilized. Additionally, we conducted stratified and interaction analyses to determine if the relationship remained consistent across different subgroups.

Results

Among 6077 participants, 267 (4.4 %) were diagnosed with ADHD. After adjustment for potential confounders, compared with individuals in the lowest tertile (T1, < 304.88 mg/kg/d) of n-6 PUFA intake, those in the second tertile (T2, 304.88–537.81 mg/kg/d) demonstrated an adjusted odds ratio (OR) of 1.55 (95 % CI: 1.26–1.92; p < 0.001) for ADHD. In contrast, participants in the highest tertile (T3, > 537.81 mg/kg/d) had an adjusted OR of 1.08 (95 % CI: 0.79–1.48; p = 0.625) .Furthermore, a significant non-linear association was observed between n-6 PUFA intake and ADHD risk (p = 0.002). Subgroup and sensitivity analyses supported the robustness of these findings.

Conclusion

Dietary n-6 PUFA intake exhibits a non-monotonic relationship with ADHD risk in US children, peaking in the middle exposure range (304.88–537.81 mg/kg/day) without significant risk at highest intakes.
目的:基于美国国家健康与营养调查(NHANES)数据,研究美国儿童和青少年饮食中n-6多不饱和脂肪酸(PUFAs)摄入与注意缺陷多动障碍(ADHD)的关系。方法:我们使用2013年至2020年NHANES的数据对6077名儿童和青少年进行了横断面分析。采用多变量logistic回归模型评估膳食n-6 PUFAs与ADHD之间的关系。为了进一步检验线性和探索剂量-响应关系的形状,我们使用了受限三次样条。此外,我们进行了分层和相互作用分析,以确定不同亚组之间的关系是否保持一致。结果:在6077名参与者中,267人(4.4%)被诊断为多动症。在对潜在混杂因素进行校正后,与n-6 PUFA摄入量最低分位(T1, < 304.88 mg/kg/d)的个体相比,第二分位(T2, 304.88-537.81 mg/kg/d)的个体ADHD的校正优势比(OR)为1.55 (95% CI: 1.26-1.92; p < 0.001)。相比之下,最高分位数(T3, bb0 537.81 mg/kg/d)的参与者的调整OR为1.08 (95% CI: 0.79-1.48; p = 0.625)。此外,n-6 PUFA摄入量与ADHD风险之间存在显著的非线性关联(p = 0.002)。亚组分析和敏感性分析支持这些发现的稳健性。结论:膳食n-6 PUFA摄入量与美国儿童ADHD风险呈非单调关系,在中等暴露范围(304.88-537.81 mg/kg/天)达到峰值,最高摄入量时无显著风险。
{"title":"The association between n-6 polyunsaturated fatty acid intakes and attention deficit hyperactivity disorder in US children and adolescents: A cross-sectional study from NHANES","authors":"Lijin Wang ,&nbsp;Qin Wang ,&nbsp;Ling Li","doi":"10.1016/j.plefa.2025.102716","DOIUrl":"10.1016/j.plefa.2025.102716","url":null,"abstract":"<div><h3>Objective</h3><div>This study aims to evaluate the relationship between dietary n-6 polyunsaturated fatty acids (PUFAs) intake and attention deficit hyperactivity disorder (ADHD) among US children and adolescents based on National Health and Nutrition Examination Survey (NHANES) data.</div></div><div><h3>Methods</h3><div>We conducted a cross-sectional analysis of 6077 children and adolescents using data from NHANES conducted between 2013 and 2020. Multivariate logistic regression models were employed to assess the association between dietary n-6 PUFAs and ADHD. To further examine linearity and explore the shape of the dose-response relationship, restricted cubic splines were utilized. Additionally, we conducted stratified and interaction analyses to determine if the relationship remained consistent across different subgroups.</div></div><div><h3>Results</h3><div>Among 6077 participants, 267 (4.4 %) were diagnosed with ADHD. After adjustment for potential confounders, compared with individuals in the lowest tertile (T1, &lt; 304.88 mg/kg/d) of n-6 PUFA intake, those in the second tertile (T2, 304.88–537.81 mg/kg/d) demonstrated an adjusted odds ratio (OR) of 1.55 (95 % CI: 1.26–1.92; p &lt; 0.001) for ADHD. In contrast, participants in the highest tertile (T3, &gt; 537.81 mg/kg/d) had an adjusted OR of 1.08 (95 % CI: 0.79–1.48; p = 0.625) .Furthermore, a significant non-linear association was observed between n-6 PUFA intake and ADHD risk (p = 0.002). Subgroup and sensitivity analyses supported the robustness of these findings.</div></div><div><h3>Conclusion</h3><div>Dietary n-6 PUFA intake exhibits a non-monotonic relationship with ADHD risk in US children, peaking in the middle exposure range (304.88–537.81 mg/kg/day) without significant risk at highest intakes.</div></div>","PeriodicalId":94179,"journal":{"name":"Prostaglandins, leukotrienes, and essential fatty acids","volume":"207 ","pages":"Article 102716"},"PeriodicalIF":3.2,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145566885","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Chronic sleep deprivation induces depression- and Alzheimer’s disease-like changes in adult and ageing wild-type and Fat-1 transgenic mice 在成年和衰老的野生型和Fat-1转基因小鼠中,慢性睡眠剥夺会引起抑郁症和阿尔茨海默病样的变化
IF 3.2 Pub Date : 2025-12-01 Epub Date: 2025-08-21 DOI: 10.1016/j.plefa.2025.102699
Nasar Ullah Khan Niazi , Zhiyou Yang , Yongping Zhang , Cai Song

Background

Sleep disorders show comorbidity with depression and Alzheimer's disease (AD), especially in ageing. However, the neuroimmunological role of sleep deprivation (SD) as possible inducer to these conditions remains unknown. Omega-3 fatty acids (n-3 FAs) can improve depression and AD through anti-inflammation, up-regulating neurotrophins and normalizing neurotransmitters, while their therapeutic effects on sleep deprivation (SD)-induced changes in different ages requires investigation.

Methods

Adult and old Fat-1 (converting n-6 to n-3 FAs) and wild-type (WT) mice were subjected to chronic SD. After behavioral evaluation, brain FAs, monoamine neurotransmitters, circadian-gene expression, TLR-4 signaling-pathway, glial polarization, cytokine profile, and AD-related markers were analyzed using GC–MS, HPLC, qPCR, ELISA and western-blotting. Furthermore, bioinformatic analysis evaluated SD-related networking with depression and AD.

Results

SD induced anxiety, anhedonia, despair, and memory impairments. The n-3:n-6 ratio, BMAL-1 gene expression, and melatonin concentration were decreased, whereas corticosterone, TLR-4, GSK3β, and NFκB concentrations increased in SD groups compared to the controls. Increased IBA-1 protein expression and proinflammatory IL-1β, TNF-α, and IL-6 concentrations were associated with decreased monoamine neuro-transmitter levels in SD groups. APP, BACE-1, RAGE and APPβ concentrations were increased, whereas LRP-1 and APPα concentrations and the APPα/APPβ ratio were decreased in SD groups than controls. These changes were more pronounced in old WT and Fat-1 animals than adults. However, compared to WT-SD, these changes were significantly ameliorated in Fat-1-SD mice, but recovery was less pronounced in old Fat-1.

Conclusion

SD-induced neuroinflammation and impaired APP processing may contribute to behavioral impairments, which exacerbated with age. Although n-3 FAs significantly ameliorated SD-induced adverse behavioral and neuroimmunological changes, this therapeutic effect was markedly reduced in old animals.
背景睡眠障碍与抑郁症和阿尔茨海默病(AD)共病,尤其是在老年人中。然而,睡眠剥夺(SD)作为可能诱发这些疾病的神经免疫学作用尚不清楚。Omega-3脂肪酸(n-3 FAs)可通过抗炎、上调神经营养因子和使神经递质正常化来改善抑郁症和AD,但其对睡眠剥夺(SD)引起的不同年龄变化的治疗效果有待研究。方法采用成年、老年Fat-1(将n-6脂肪酸转化为n-3脂肪酸)和野生型(WT)小鼠进行慢性SD治疗。行为评估后,采用GC-MS、HPLC、qPCR、ELISA和western-blotting分析脑FAs、单胺类神经递质、昼夜节律基因表达、TLR-4信号通路、胶质极化、细胞因子谱和ad相关标志物。此外,生物信息学分析评估了sd与抑郁症和AD的相关网络。结果ssd引起焦虑、快感缺乏、绝望和记忆障碍。SD组的n-3:n-6比值、BMAL-1基因表达和褪黑激素浓度降低,皮质酮、TLR-4、GSK3β和NFκB浓度升高。SD组IBA-1蛋白表达和促炎IL-1β、TNF-α和IL-6浓度升高与单胺类神经递质水平降低有关。SD组的APP、BACE-1、RAGE和APPβ浓度均升高,LRP-1和APPα浓度及APPα/APPβ比值均低于对照组。这些变化在老年WT和Fat-1动物中比成年动物更明显。然而,与WT-SD相比,Fat-1- sd小鼠的这些变化明显改善,但Fat-1小鼠的恢复不太明显。结论sd诱导的神经炎症和APP加工受损可能导致行为障碍,且随年龄增长而加重。虽然n-3脂肪酸显著改善sd诱导的不良行为和神经免疫变化,但这种治疗效果在老年动物中明显降低。
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引用次数: 0
Impact of n-3 polyunsaturate fatty acids supplementation on visual health throughout the life cycle: A systematic review 补充n-3多不饱和脂肪酸对整个生命周期视觉健康的影响:系统综述
IF 3 Pub Date : 2025-10-01 Epub Date: 2025-05-27 DOI: 10.1016/j.plefa.2025.102686
Claudia Tabilo , Valentina Squella , Paola Illesca , Yasna Muñoz , Camila Farías , Rodrigo Valenzuela

Introduction

N-3 polyunsaturated fatty acids (n-3 PUFA) are important for mammals and have relevant functions in the body. These fatty acids play an important role in brain development, in the protection of the retina, and in the prevention of macular degeneration. Currently, clinical trials do not yet confirm a clear benefit of n-3 PUFA supplementation on vision throughout the life cycle. Therefore, the aim of this study is to systematically evaluate the available scientific evidence to determine the effects of n-3 PUFA supplementation on visual health throughout the life cycle.

Material and Methods

A search of scientific literature was performed, based on randomized, controlled clinical studies, published in PubMed, using keywords. We included people of both sexes throughout the life cycle that evaluated the impact of n-3 PUFA supplementation on visual health.

Results

Of the 87 articles included in this review, there are important contradictions in the literature regarding the effects of supplementation in pregnant women, infants and older adults. While some studies highlight beneficial effects, an equal number of studies report no impact. In the case of preschoolers and schoolchildren, predominantly positive effects were identified, especially in children with Attention Deficit Hyperactivity Disorder (ADHD). For youth and adults, the impact of supplementation varied according to the health condition assessed, mostly supporting significant benefits in individuals with dry eye symptoms.

Conclusion

Evidence supports supplementation with n-3 PUFA, especially docosahexaenoic acid (DHA), to improve visual development in infants, schoolchildren, especially those with ADHD. Despite variability in visual outcomes, these findings suggest a crucial role of n-3 PUFA supplementation in visual health in the first steps of life, but in adults and older adults remain uncertain or null. Therefore, it is critical to investigate optimal dosing, duration of the intervention as the age of the participants in future research.
n-3多不饱和脂肪酸(n-3 PUFA)在哺乳动物体内具有重要的功能。这些脂肪酸在大脑发育、保护视网膜和预防黄斑变性方面发挥着重要作用。目前,临床试验尚未证实n-3 PUFA补充剂在整个生命周期内对视力的明显益处。因此,本研究的目的是系统地评估现有的科学证据,以确定补充n-3 PUFA对整个生命周期视觉健康的影响。材料和方法基于PubMed上发表的随机对照临床研究,使用关键词对科学文献进行检索。我们纳入了在整个生命周期中评估n-3 PUFA补充对视觉健康影响的男性和女性。结果在本综述纳入的87篇文章中,关于孕妇、婴儿和老年人补充叶酸的效果,文献中存在重要的矛盾。虽然一些研究强调了有益的影响,但同样数量的研究报告没有影响。在学龄前儿童和学龄儿童中,主要是积极的影响,特别是在患有注意力缺陷多动障碍(ADHD)的儿童中。对于青少年和成年人,补充维生素d的影响根据评估的健康状况而有所不同,主要支持对有干眼症状的个体的显着益处。结论有证据支持补充n-3 PUFA,特别是二十二碳六烯酸(DHA)可改善婴幼儿、学龄儿童,尤其是ADHD儿童的视力发育。尽管视力结果存在差异,但这些发现表明,在生命的最初阶段,补充n-3 PUFA对视力健康起着至关重要的作用,但在成年人和老年人中仍然不确定或无效。因此,在未来的研究中,研究最佳剂量、干预持续时间随参与者年龄的变化是至关重要的。
{"title":"Impact of n-3 polyunsaturate fatty acids supplementation on visual health throughout the life cycle: A systematic review","authors":"Claudia Tabilo ,&nbsp;Valentina Squella ,&nbsp;Paola Illesca ,&nbsp;Yasna Muñoz ,&nbsp;Camila Farías ,&nbsp;Rodrigo Valenzuela","doi":"10.1016/j.plefa.2025.102686","DOIUrl":"10.1016/j.plefa.2025.102686","url":null,"abstract":"<div><h3>Introduction</h3><div>N-3 polyunsaturated fatty acids (n-3 PUFA) are important for mammals and have relevant functions in the body. These fatty acids play an important role in brain development, in the protection of the retina, and in the prevention of macular degeneration. Currently, clinical trials do not yet confirm a clear benefit of n-3 PUFA supplementation on vision throughout the life cycle. Therefore, the aim of this study is to systematically evaluate the available scientific evidence to determine the effects of n-3 PUFA supplementation on visual health throughout the life cycle.</div></div><div><h3>Material and Methods</h3><div>A search of scientific literature was performed, based on randomized, controlled clinical studies, published in PubMed, using keywords. We included people of both sexes throughout the life cycle that evaluated the impact of n-3 PUFA supplementation on visual health.</div></div><div><h3>Results</h3><div>Of the 87 articles included in this review, there are important contradictions in the literature regarding the effects of supplementation in pregnant women, infants and older adults. While some studies highlight beneficial effects, an equal number of studies report no impact. In the case of preschoolers and schoolchildren, predominantly positive effects were identified, especially in children with Attention Deficit Hyperactivity Disorder (ADHD). For youth and adults, the impact of supplementation varied according to the health condition assessed, mostly supporting significant benefits in individuals with dry eye symptoms.</div></div><div><h3>Conclusion</h3><div>Evidence supports supplementation with n-3 PUFA, especially docosahexaenoic acid (DHA), to improve visual development in infants, schoolchildren, especially those with ADHD. Despite variability in visual outcomes, these findings suggest a crucial role of n-3 PUFA supplementation in visual health in the first steps of life, but in adults and older adults remain uncertain or null. Therefore, it is critical to investigate optimal dosing, duration of the intervention as the age of the participants in future research.</div></div>","PeriodicalId":94179,"journal":{"name":"Prostaglandins, leukotrienes, and essential fatty acids","volume":"206 ","pages":"Article 102686"},"PeriodicalIF":3.0,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144253997","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Unravelling the complex interplay between zinc, iron and their synergistic effect on LCPUFA metabolism in preeclampsia 揭示锌、铁之间的复杂相互作用及其对子痫前期LCPUFA代谢的协同作用
IF 3.2 Pub Date : 2025-10-01 Epub Date: 2025-08-14 DOI: 10.1016/j.plefa.2025.102701
Vaishnavi Mudgal, Juhi Nema, Sadhana Joshi
Preeclampsia is a hypertensive disorder of pregnancy. It is a leading cause of maternal mortality and morbidity. Long-chain polyunsaturated fatty acids (LCPUFAs) are critical for normal placental and fetal development. Biosynthesis of these LCPUFAs is regulated by Δ5 and Δ6 desaturase enzymes, which require zinc and iron as cofactors. Both zinc and iron are important micronutrients which play pivotal role during pregnancy and their deficiency during pregnancy is linked with preeclampsia. Zinc and iron deficiency is common in pregnancy and often coexists. Zinc and iron interact in complex ways, influencing the bioavailability of each other. On the other hand, zinc is required for intestinal uptake and transport of iron. The current article summarizes studies examining the role of zinc, iron and LCPUFAs in preeclampsia. It also gives a mechanistic insight through which zinc and iron synergistically influence LCPUFA biosynthesis in pregnancy complicated with preeclampsia.
子痫前期是妊娠期高血压疾病。它是孕产妇死亡和发病的主要原因。长链多不饱和脂肪酸(LCPUFAs)对胎盘和胎儿的正常发育至关重要。这些LCPUFAs的生物合成是由Δ5和Δ6去饱和酶调节的,它们需要锌和铁作为辅助因子。锌和铁都是重要的微量元素,在怀孕期间起着关键作用,怀孕期间缺乏锌和铁与先兆子痫有关。锌和铁缺乏症在怀孕期间很常见,而且经常共存。锌和铁以复杂的方式相互作用,影响彼此的生物利用度。另一方面,锌是肠内铁的吸收和运输所必需的。本文综述了锌、铁和LCPUFAs在子痫前期的作用。它也提供了一个机制的见解,通过锌和铁协同影响LCPUFA生物合成在妊娠合并先兆子痫。
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引用次数: 0
Early-life feeding of arachidonic acid and docosahexaenoic acid beneficially modulated ileum and splenocyte oxylipins to support oral tolerance development in allergy-prone BALB/c mice 早期喂养花生四烯酸和二十二碳六烯酸有利于调节回肠和脾细胞氧脂,以支持易过敏BALB/c小鼠的口服耐受性发展
IF 3 Pub Date : 2025-10-01 Epub Date: 2025-05-23 DOI: 10.1016/j.plefa.2025.102689
Ren Wang, Dhruvesh Patel, Susan Goruk, Magaly Rivas Serna, Vera Mazurak, Caroline Richard, Catherine Field

Background

Early-life feeding of arachidonic acid (ARA)+docosahexaenoic acid (DHA) has been shown to promote immune changes associated with oral tolerance (OT). Oxylipins have been demonstrated to be modulated by diet and alter immune function.

Objective

To determine whether early-life feeding of ARA+DHA modulated the ileum and ovalbumin (OVA)-challenged splenocyte oxylipin profile in a way that is beneficial for OT development.

Method

Allergy-prone BALB/c dams were fed a control (0 %ARA, 0 %DHA) or ARA+DHA (1 %ARA, 1 %DHA) diet during suckling. At 3wks, half of the pups were killed to analyze ileum morphology and oxylipin profile. The remaining pups continued consuming the maternal diets. From day 21–25, pups received daily oral gavage of sucrose or OVA, followed by intraperitoneal OVA injections on day 35 and 41. At 6wks, pups were killed to analyze plasma OVA-specific-IgE and -IgG, ileum morphology, splenocyte phospholipid fatty acid composition and ex vivo splenocyte oxylipin production after OVA stimulation.

Results

ARA+DHA supplementation resulted in a 5-fold reduction in plasma OVA-IgE concentration, confirming OT development. At 3wks, ARA+DHA-fed mice had higher ileum levels of 8-HETE, 14,15-DiHETrE, 4-HDHA, 17-HDHA and 19,20-EpDPE and lower levels of 13-HODE and 20-HETE, which suggests better ileum maturation, lower inflammation and enhanced tolerogenic immune regulation to support OT. The longer villi, shorter crypts and higher villus/crypt ratio confirmed the superior ileum maturation. At 6wks, ARA+DHA supplementation increased oxylipin substrates (ARA, DHA, linoleic acid and eicosapentaenoic acid) in splenocyte phospholipids. After OVA stimulation, splenocytes from ARA+DHA-fed mice produced more PGD2, 5-HETE, 15-HETE and 20-HDHA and less TXB2 and 12-HETE, which suggests inhibited Th2 and allergic responses and enhanced tolerogenic immune modulation to support OT.

Conclusion

Early-life feeding of ARA+DHA beneficially modulated the oxylipin profile in the ileum and OVA-challenged splenocytes to support OT development.
幼儿喂养花生四烯酸(ARA)+二十二碳六烯酸(DHA)已被证明可促进与口服耐受性(OT)相关的免疫变化。氧脂素已被证明可以通过饮食调节并改变免疫功能。目的探讨早期喂养ARA+DHA是否能调节回肠和卵清蛋白(OVA)挑战的脾细胞氧脂谱,从而有利于OT的发展。方法在哺乳期给易过敏BALB/c母鼠饲喂对照组(0% ARA, 0% DHA)或ARA+DHA (1% ARA, 1% DHA)饲粮。在3周时,杀死一半的幼崽,分析回肠形态和氧脂质谱。剩下的幼崽继续吃母鼠的食物。第21-25天,每天灌胃蔗糖或卵细胞,第35天和第41天分别腹腔注射卵细胞。6周时,处死幼崽,分析卵细胞刺激后血浆卵细胞特异性ige和igg、回肠形态、脾细胞磷脂脂肪酸组成和体外脾细胞氧脂生成。结果补充sara +DHA导致血浆OVA-IgE浓度降低5倍,证实了OT的发生。在3周时,ARA+ dha喂养的小鼠回肠中8-HETE、14,15- dihetre、4-HDHA、17-HDHA和19,20- epdpe水平较高,13-HODE和20-HETE水平较低,这表明回肠成熟程度更高,炎症程度更低,耐受性免疫调节增强,支持OT。较长的绒毛,较短的隐窝和较高的绒毛/隐窝比证实了上回肠的成熟。在6周时,补充ARA+DHA增加了脾细胞磷脂中的氧化脂质底物(ARA、DHA、亚油酸和二十碳五烯酸)。卵子刺激后,ARA+ dha喂养小鼠脾细胞产生更多的PGD2、5-HETE、15-HETE和20-HDHA,减少TXB2和12-HETE,这表明抑制Th2和过敏反应,增强耐受性免疫调节,支持OT。结论早期喂养ARA+DHA有利于调节回肠和ova刺激的脾细胞中的氧脂质分布,支持OT的发展。
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引用次数: 0
Dysfunction of COX-2/mPGES-1/PGE2 pathway and EP4 receptor in bronchi from COPD patients COPD患者支气管COX-2/mPGES-1/PGE2通路及EP4受体功能障碍
IF 3 Pub Date : 2025-10-01 Epub Date: 2025-05-24 DOI: 10.1016/j.plefa.2025.102685
Salma Mani , Zhipeng Li , Hichem Badji , Gaelle Merheb , Sébastien Dupont , Yves Castier , Olivier Thibaudeau , Mathilde Varret , Alice Guyard , Dan Longrois , Xavier Norel
Progressive airflow obstruction and chronic lung inflammation are hallmarks of chronic obstructive pulmonary disease (COPD). Prostaglandin E2 (PGE2), synthesized by the cyclooxygenase-2 (COX-2) and microsomal prostaglandin E synthase-1 (mPGES-1), acts as a lipid mediator with bronchodilatory effects mediated by the EP4 receptor. Altered expression and function of COX-2, mPGES-1, PGE2 and EP receptors may contribute to the pathophysiology of COPD. This study investigates whether COPD is associated with dysregulated expression or function of COX-2, mPGES-1, EP receptors and PGE2 production in human bronchi. We analyzed the expression of COX-2, mPGES-1, PGE2 and EP receptors in human bronchi samples using Western blot, real-time qPCR, ELISA and immunohistochemistry (IHC). Our results reveal significantly elevated COX-2 protein, mPGES-1 mRNA, and PGE2 levels in COPD patients compared to controls. Conversely, in COPD preparations EP4 receptor mRNA and protein levels were markedly reduced, a result confirmed by IHC. In addition, IHC also showed that the EP4 receptor was mainly localized in the epithelium of control bronchi. Notably, there was a significant negative correlation between EP4 and PGE2 levels. The hypothesis of EP4 internalization due to increased PGE2 in COPD patients is credible. These data demonstrate a significant alteration of the COX-2/mPGES-1/PGE2/EP4 pathway in COPD and suggest that pharmacological targeting of this pathway may be of interest to treat COPD.
进行性气流阻塞和慢性肺部炎症是慢性阻塞性肺疾病(COPD)的标志。前列腺素E2 (PGE2)由环氧化酶-2 (COX-2)和微粒体前列腺素E合成酶-1 (mPGES-1)合成,是一种脂质介质,在EP4受体介导下具有支气管扩张作用。COX-2、mPGES-1、PGE2和EP受体的表达和功能改变可能与COPD的病理生理有关。本研究探讨COPD是否与人支气管COX-2、mPGES-1、EP受体和PGE2生成的表达或功能失调有关。采用Western blot、real-time qPCR、ELISA和免疫组化(IHC)技术分析人支气管组织中COX-2、mPGES-1、PGE2和EP受体的表达。我们的研究结果显示,与对照组相比,COPD患者的COX-2蛋白、mPGES-1 mRNA和PGE2水平显著升高。相反,在COPD制剂中,EP4受体mRNA和蛋白水平明显降低,IHC证实了这一结果。此外,IHC还显示EP4受体主要定位于对照支气管上皮。EP4与PGE2呈显著负相关。COPD患者PGE2升高导致EP4内化的假设是可信的。这些数据证明了COX-2/mPGES-1/PGE2/EP4通路在COPD中的显著改变,并提示该通路的药理靶向可能是治疗COPD的兴趣。
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引用次数: 0
期刊
Prostaglandins, leukotrienes, and essential fatty acids
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