Pub Date : 2025-08-14DOI: 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.
{"title":"Unravelling the complex interplay between zinc, iron and their synergistic effect on LCPUFA metabolism in preeclampsia","authors":"Vaishnavi Mudgal, Juhi Nema, Sadhana Joshi","doi":"10.1016/j.plefa.2025.102701","DOIUrl":"10.1016/j.plefa.2025.102701","url":null,"abstract":"<div><div>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.</div></div>","PeriodicalId":94179,"journal":{"name":"Prostaglandins, leukotrienes, and essential fatty acids","volume":"206 ","pages":"Article 102701"},"PeriodicalIF":3.2,"publicationDate":"2025-08-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144885393","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}
Pub Date : 2025-07-23DOI: 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.
{"title":"Predictive role of erythrocyte fatty acids in conversion to psychosis: a longitudinal study of clinical high-risk individuals","authors":"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","doi":"10.1016/j.plefa.2025.102698","DOIUrl":"10.1016/j.plefa.2025.102698","url":null,"abstract":"<div><h3>Introduction</h3><div>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).</div></div><div><h3>Materials and methods</h3><div>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.</div></div><div><h3>Results</h3><div>CHR-C individuals exhibited higher levels of Eicosenoic acid(<em>p</em> = 0.016), Linoleic acid(<em>p</em> = 0.009), Eicosadienoic acid(<em>p</em> = 0.035) and Arachidonic acid(<em>p</em> = 0.037) compared to CHR-NC, whereas CHR individuals showed elevated levels of Palmitoleic acid(<em>p</em> = 0.002), Palmitic acid(<em>p</em> = 0.012), Eicosapentaenoic acid(<em>p</em> = 0.019) and Oleic acid(<em>p</em> = 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.</div></div><div><h3>Discussion</h3><div>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.</div></div>","PeriodicalId":94179,"journal":{"name":"Prostaglandins, leukotrienes, and essential fatty acids","volume":"206 ","pages":"Article 102698"},"PeriodicalIF":3.0,"publicationDate":"2025-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144711809","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}
Pub Date : 2025-06-27DOI: 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.
{"title":"Sex and dietary ALA and DHA effects on rat heart phospholipase A2 activity mediating fatty acid release and oxylipin formation have cardiovascular implications","authors":"Anne Manson , Tanja Winter , Harold M. Aukema","doi":"10.1016/j.plefa.2025.102697","DOIUrl":"10.1016/j.plefa.2025.102697","url":null,"abstract":"<div><div>The ways in which diet and sex influence heart phospholipase A<sub>2</sub> (PLA<sub>2</sub>) 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)PLA<sub>2</sub> (Varespladib) or calcium-independent (i)PLA<sub>2</sub> (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. sPLA<sub>2</sub> 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 iPLA<sub>2</sub>. iPLA<sub>2</sub> activity was less selective, with activity towards all measured PUFA and oxylipins, with the primary PUFA released depending on diet. For both sPLA<sub>2</sub> and iPLA<sub>2</sub>, 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 PLA<sub>2</sub> types in cardiovascular oxylipin biology.</div></div>","PeriodicalId":94179,"journal":{"name":"Prostaglandins, leukotrienes, and essential fatty acids","volume":"206 ","pages":"Article 102697"},"PeriodicalIF":3.0,"publicationDate":"2025-06-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144587760","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}
Pub Date : 2025-06-27DOI: 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。
{"title":"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","authors":"Callum J. Pufahl , Sydney E. Smart , Justin Bureau , Brendan Ross , Craig A. Simpson , Adam H. Metherel , James R. Dick , Chris McGlory","doi":"10.1016/j.plefa.2025.102696","DOIUrl":"10.1016/j.plefa.2025.102696","url":null,"abstract":"<div><div>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 (<em>p</em>= 0.035) at 6 weeks of supplementation, higher erythrocyte EPA phospholipid composition (<em>p</em>= 0.034), and whole plasma DHA composition (<em>p</em>= 0.033) compared to males. At 14 weeks of washout, skeletal muscle and erythrocyte EPA phospholipid composition (<em>p</em>< 0.001 and <em>p</em>= 0.005) remained elevated above baseline, whereas whole plasma EPA composition (<em>p</em>= 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.</div></div>","PeriodicalId":94179,"journal":{"name":"Prostaglandins, leukotrienes, and essential fatty acids","volume":"206 ","pages":"Article 102696"},"PeriodicalIF":3.0,"publicationDate":"2025-06-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144614712","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}
Pub Date : 2025-05-29DOI: 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.
{"title":"Linoleic acid promotes mammary tumor growth and metastasis to brain and lung in female Balb/cJ mice","authors":"Maria Sanchez-Juarez , Monica Vizcarra-Soto , Rocio Castillo-Sanchez , Pablo Torres-Alamilla , Pedro Cortes-Reynosa , Gustavo Acosta-Altamirano , Monica Sierra-Martinez , Eduardo Perez Salazar","doi":"10.1016/j.plefa.2025.102687","DOIUrl":"10.1016/j.plefa.2025.102687","url":null,"abstract":"<div><div>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.</div></div>","PeriodicalId":94179,"journal":{"name":"Prostaglandins, leukotrienes, and essential fatty acids","volume":"206 ","pages":"Article 102687"},"PeriodicalIF":3.0,"publicationDate":"2025-05-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144205319","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}
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.
{"title":"Impact of n-3 polyunsaturate fatty acids supplementation on visual health throughout the life cycle: A systematic review","authors":"Claudia Tabilo , Valentina Squella , Paola Illesca , Yasna Muñoz , Camila Farías , 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":"2025-05-27","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}
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.
{"title":"Dysfunction of COX-2/mPGES-1/PGE2 pathway and EP4 receptor in bronchi from COPD patients","authors":"Salma Mani , Zhipeng Li , Hichem Badji , Gaelle Merheb , Sébastien Dupont , Yves Castier , Olivier Thibaudeau , Mathilde Varret , Alice Guyard , Dan Longrois , Xavier Norel","doi":"10.1016/j.plefa.2025.102685","DOIUrl":"10.1016/j.plefa.2025.102685","url":null,"abstract":"<div><div>Progressive airflow obstruction and chronic lung inflammation are hallmarks of chronic obstructive pulmonary disease (COPD). Prostaglandin E2 (PGE<sub>2</sub>), 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, PGE<sub>2</sub> 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 PGE<sub>2</sub> production in human bronchi. We analyzed the expression of COX-2, mPGES-1, PGE<sub>2</sub> 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 PGE<sub>2</sub> 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 PGE<sub>2</sub> levels. The hypothesis of EP4 internalization due to increased PGE<sub>2</sub> in COPD patients is credible. These data demonstrate a significant alteration of the COX-2/mPGES-1/PGE<sub>2</sub>/EP4 pathway in COPD and suggest that pharmacological targeting of this pathway may be of interest to treat COPD.</div></div>","PeriodicalId":94179,"journal":{"name":"Prostaglandins, leukotrienes, and essential fatty acids","volume":"206 ","pages":"Article 102685"},"PeriodicalIF":3.0,"publicationDate":"2025-05-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144270423","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}
Pub Date : 2025-05-23DOI: 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.
{"title":"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","authors":"Ren Wang, Dhruvesh Patel, Susan Goruk, Magaly Rivas Serna, Vera Mazurak, Caroline Richard, Catherine Field","doi":"10.1016/j.plefa.2025.102689","DOIUrl":"10.1016/j.plefa.2025.102689","url":null,"abstract":"<div><h3>Background</h3><div>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.</div></div><div><h3>Objective</h3><div>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.</div></div><div><h3>Method</h3><div>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 <em>ex vivo</em> splenocyte oxylipin production after OVA stimulation.</div></div><div><h3>Results</h3><div>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.</div></div><div><h3>Conclusion</h3><div>Early-life feeding of ARA+DHA beneficially modulated the oxylipin profile in the ileum and OVA-challenged splenocytes to support OT development.</div></div>","PeriodicalId":94179,"journal":{"name":"Prostaglandins, leukotrienes, and essential fatty acids","volume":"206 ","pages":"Article 102689"},"PeriodicalIF":3.0,"publicationDate":"2025-05-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144146810","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}
Pub Date : 2025-05-23DOI: 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.
{"title":"Fatty acid tissue composition in mice fed diets containing varying levels of Omega-3 fatty acids","authors":"Nahed Hussein , Irina Dahms , Norman Salem Jr.","doi":"10.1016/j.plefa.2025.102688","DOIUrl":"10.1016/j.plefa.2025.102688","url":null,"abstract":"<div><div>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.</div></div>","PeriodicalId":94179,"journal":{"name":"Prostaglandins, leukotrienes, and essential fatty acids","volume":"206 ","pages":"Article 102688"},"PeriodicalIF":3.0,"publicationDate":"2025-05-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144212514","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}
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.
{"title":"Association of birth outcomes with maternal and infant FADS1 rs174547 genotypes in Japanese participants","authors":"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","doi":"10.1016/j.plefa.2025.102683","DOIUrl":"10.1016/j.plefa.2025.102683","url":null,"abstract":"<div><div>N-3 long-chain polyunsaturated fatty acids (n-3LCPUFAs) are crucial for child growth and development particularly for fetal growth <em>in utero</em> and brain development and function. This study examined the relationship between birth outcomes and <em>FADS1</em> 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 <em>FADS1</em> genotypes may influence fetal growth. Furthermore, in <em>FADS1</em> 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 <em>FADS1</em> 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.</div></div>","PeriodicalId":94179,"journal":{"name":"Prostaglandins, leukotrienes, and essential fatty acids","volume":"206 ","pages":"Article 102683"},"PeriodicalIF":3.0,"publicationDate":"2025-04-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144123232","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}
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