Pub Date : 2024-04-01DOI: 10.1016/j.plefa.2024.102655
Jisun So , Jonathan H. Yao , Rozana Magadmi , Nirupa R. Matthan , Stefania Lamon-Fava
The rate of cardiovascular disease (CVD) death is higher in men than women before age 50 y, but the gap between sexes significantly narrows after menopause. Lipid mediators derived from EPA, DHA and AA play a role in inflammation and CVD. The aim of our study was to assess whether plasma concentrations of these lipid mediators differ between postmenopausal women and men. Twelve postmenopausal women and 9 men with low-grade chronic inflammation completed a randomized, double-blind, crossover study consisting of a 4-week lead-in placebo phase (3 g/d high-oleic acid sunflower oil) followed by randomization to either 3 g/d DHA or 3 g/d EPA for 10 weeks and crossover for additional 10 weeks, separated by a washout phase. Plasma phospholipid content of EPA, DHA and AA and plasma concentrations of their derived lipid mediators were measured at the end of the placebo lead-in phase (baseline) and the DHA and EPA supplementation phases. There were no sex differences in plasma phospholipid EPA, DHA and AA at baseline and after DHA and EPA supplementation. However, plasma concentrations of lipid mediators derived from EPA, DHA and AA via 15-lipoxygenase were lower in postmenopausal women than men, especially after supplementation. Sex differences in EPA- and DHA-derived lipid mediators with anti-inflammatory and pro-resolving actions may partly explain the faster rise in CVD in postmenopausal women than age-matched men.
50 岁之前，男性的心血管疾病（CVD）死亡率高于女性，但绝经后男女之间的差距明显缩小。源自 EPA、DHA 和 AA 的脂质介质在炎症和心血管疾病中发挥着作用。我们的研究旨在评估绝经后女性和男性血浆中这些脂质介质的浓度是否存在差异。12 名绝经后女性和 9 名患有低度慢性炎症的男性完成了一项随机、双盲、交叉研究，该研究包括一个为期 4 周的先导安慰剂阶段（3 克/天高油酸葵花籽油），然后随机服用 3 克/天 DHA 或 3 克/天 EPA，为期 10 周，再交叉服用 10 周，中间有一个冲洗阶段。在安慰剂诱导阶段（基线）以及 DHA 和 EPA 补充阶段结束时，测量血浆中 EPA、DHA 和 AA 的磷脂含量及其衍生脂质介质的血浆浓度。在基线和补充 DHA 和 EPA 后，血浆磷脂 EPA、DHA 和 AA 没有性别差异。然而，绝经后女性血浆中通过 15-脂氧合酶从 EPA、DHA 和 AA 中提取的脂质介质浓度低于男性，尤其是在补充后。EPA和DHA衍生的脂质介质具有抗炎和促进溶解作用，其性别差异可能是绝经后女性心血管疾病发病率上升快于年龄匹配男性的部分原因。
{"title":"Sex differences in lipid mediators derived from omega-3 fatty acids in older individuals with low-grade chronic inflammation","authors":"Jisun So , Jonathan H. Yao , Rozana Magadmi , Nirupa R. Matthan , Stefania Lamon-Fava","doi":"10.1016/j.plefa.2024.102655","DOIUrl":"10.1016/j.plefa.2024.102655","url":null,"abstract":"<div><div>The rate of cardiovascular disease (CVD) death is higher in men than women before age 50 y, but the gap between sexes significantly narrows after menopause. Lipid mediators derived from EPA, DHA and AA play a role in inflammation and CVD. The aim of our study was to assess whether plasma concentrations of these lipid mediators differ between postmenopausal women and men. Twelve postmenopausal women and 9 men with low-grade chronic inflammation completed a randomized, double-blind, crossover study consisting of a 4-week lead-in placebo phase (3 g/d high-oleic acid sunflower oil) followed by randomization to either 3 g/d DHA or 3 g/d EPA for 10 weeks and crossover for additional 10 weeks, separated by a washout phase. Plasma phospholipid content of EPA, DHA and AA and plasma concentrations of their derived lipid mediators were measured at the end of the placebo lead-in phase (baseline) and the DHA and EPA supplementation phases. There were no sex differences in plasma phospholipid EPA, DHA and AA at baseline and after DHA and EPA supplementation. However, plasma concentrations of lipid mediators derived from EPA, DHA and AA via 15-lipoxygenase were lower in postmenopausal women than men, especially after supplementation. Sex differences in EPA- and DHA-derived lipid mediators with anti-inflammatory and pro-resolving actions may partly explain the faster rise in CVD in postmenopausal women than age-matched men.</div></div>","PeriodicalId":94179,"journal":{"name":"Prostaglandins, leukotrienes, and essential fatty acids","volume":"203 ","pages":"Article 102655"},"PeriodicalIF":3.0,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142570813","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 : 2024-04-01DOI: 10.1016/j.plefa.2024.102651
M. Banic , M. van Dijk , F.J. Dijk , M.J.W. Furber , O.C. Witard , N. Donker , M.J.A. Becker , S.D. Galloway , N. Rodriguez-Sanchez
We demonstrate divergent incorporation and washout patterns for EPA and DHA following high and low-dose EPA+DHA incubation in C2C12 myotubes, with higher concentrations favoring n-3 PUFA incorporation. Lower n-3 PUFA concentrations increased MPS without further upregulating the mTORC1 signaling pathway. Our study provides novel insights into the temporal incorporation and washout dynamics of EPA and DHA and, specifically, their combined effect on MPS, thereby advancing knowledge regarding dietary n-3 PUFA prescription to promote skeletal muscle health in humans.
{"title":"Dose-dependency of a combined EPA:DHA mixture on incorporation, washout, and protein synthesis in C2C12 myotubes","authors":"M. Banic , M. van Dijk , F.J. Dijk , M.J.W. Furber , O.C. Witard , N. Donker , M.J.A. Becker , S.D. Galloway , N. Rodriguez-Sanchez","doi":"10.1016/j.plefa.2024.102651","DOIUrl":"10.1016/j.plefa.2024.102651","url":null,"abstract":"<div><div>We demonstrate divergent incorporation and washout patterns for EPA and DHA following high and low-dose EPA+DHA incubation in C2C12 myotubes, with higher concentrations favoring <em>n</em>-3 PUFA incorporation. Lower <em>n</em>-3 PUFA concentrations increased MPS without further upregulating the mTORC1 signaling pathway. Our study provides novel insights into the temporal incorporation and washout dynamics of EPA and DHA and, specifically, their combined effect on MPS, thereby advancing knowledge regarding dietary <em>n</em>-3 PUFA prescription to promote skeletal muscle health in humans.</div></div>","PeriodicalId":94179,"journal":{"name":"Prostaglandins, leukotrienes, and essential fatty acids","volume":"203 ","pages":"Article 102651"},"PeriodicalIF":3.0,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142635240","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Docosahexaenoic acid (DHA) and arachidonic acid (ARA) are relevant polyunsaturated fatty acids (PUFA) derived from alpha-linolenic acid (ALA) and linoleic acid (LA), respectively. These are important in pregnancy and lactation periods because of their benefits to the developing fetus and infant. Currently, the high prevalence of gestational obesity has led to a revision of PUFAs recommendations in these periods, due to changes in the lipid profile of women marked by a higher consumption of n-6 PUFA.
Objective
This review aims to present an updated compilation of evidence on DHA and ARA during gestation and lactation.
Methods
The literature review was performed in different databases, PubMed, Scopus, Web of Science, Scielo, ISI, and Ovid MedLine, highlighting the importance of DHA and ARA for newborn development.
Results
An adequate intake of n-3 PUFA, especially DHA, in the mother during pregnancy and the postnatal period is important for the normal development of the child's brain. Maternal DHA supplementation increases DHA levels in mothers, but its direct link to infant neurodevelopment remains unclear. Obesity generates changes in the FA profile of pregnant women, causing an imbalance of n-3 and n-6 PUFA. An adequate level of DHA benefits children's cognitive function. However, a potential connection exists to the infants' inflammatory profile.
Conclusion
During gestation and lactation periods, an adequate DHA intake and n-6/ n-3 PUFA ratio (especially for obese women) are important for the optimal growth and brain development of the child.
背景二十二碳六烯酸（DHA）和花生四烯酸（ARA）是分别从α-亚麻酸（ALA）和亚油酸（LA）中提取的相关多不饱和脂肪酸（PUFA）。由于这些脂肪酸对发育中的胎儿和婴儿有益，因此在孕期和哺乳期非常重要。目前，由于妊娠期肥胖症的高发率，导致对这些时期的 PUFAs 推荐值进行了修订，原因是妇女的血脂状况发生了变化，n-6 PUFA 的摄入量增加。结果母亲在孕期和产后摄入充足的 n-3 PUFA（尤其是 DHA）对儿童大脑的正常发育非常重要。补充母体 DHA 可提高母亲体内的 DHA 水平，但其与婴儿神经发育的直接联系仍不清楚。肥胖会改变孕妇的脂肪酸组成，导致 n-3 和 n-6 PUFA 失衡。充足的 DHA 有利于儿童的认知功能。结论在妊娠期和哺乳期，充足的 DHA 摄入量和 n-6/ n-3 PUFA 比例（尤其是肥胖妇女）对儿童的最佳生长和大脑发育非常重要。
{"title":"Impact of polyunsaturated fatty acids during and pregnancy and lactation: A comprehensive review","authors":"Yasna Muñoz , Lorena Mercado , Camila Farias , María Paz Beyer , Ignacio Alvear , Francisca Echeverría , Rodrigo Valenzuela","doi":"10.1016/j.plefa.2024.102656","DOIUrl":"10.1016/j.plefa.2024.102656","url":null,"abstract":"<div><h3>Background</h3><div>Docosahexaenoic acid (DHA) and arachidonic acid (ARA) are relevant polyunsaturated fatty acids (PUFA) derived from alpha-linolenic acid (ALA) and linoleic acid (LA), respectively. These are important in pregnancy and lactation periods because of their benefits to the developing fetus and infant. Currently, the high prevalence of gestational obesity has led to a revision of PUFAs recommendations in these periods, due to changes in the lipid profile of women marked by a higher consumption of n-6 PUFA.</div></div><div><h3>Objective</h3><div>This review aims to present an updated compilation of evidence on DHA and ARA during gestation and lactation.</div></div><div><h3>Methods</h3><div>The literature review was performed in different databases, PubMed, Scopus, Web of Science, Scielo, ISI, and Ovid MedLine, highlighting the importance of DHA and ARA for newborn development.</div></div><div><h3>Results</h3><div>An adequate intake of n-3 PUFA, especially DHA, in the mother during pregnancy and the postnatal period is important for the normal development of the child's brain. Maternal DHA supplementation increases DHA levels in mothers, but its direct link to infant neurodevelopment remains unclear. Obesity generates changes in the FA profile of pregnant women, causing an imbalance of n-3 and n-6 PUFA. An adequate level of DHA benefits children's cognitive function. However, a potential connection exists to the infants' inflammatory profile.</div></div><div><h3>Conclusion</h3><div>During gestation and lactation periods, an adequate DHA intake and n-6/ n-3 PUFA ratio (especially for obese women) are important for the optimal growth and brain development of the child.</div></div>","PeriodicalId":94179,"journal":{"name":"Prostaglandins, leukotrienes, and essential fatty acids","volume":"203 ","pages":"Article 102656"},"PeriodicalIF":3.0,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142554636","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 : 2024-04-01DOI: 10.1016/j.plefa.2024.102653
Lea Gründler , Philine Beinhorn , Andreas Hahn , Jan Philipp Schuchardt
Long-chain omega-3 polyunsaturated fatty acids (n-3 PUFAs), specifically eicosapentaenoic acid (EPA, C20:5n-3) and docosahexaenoic acid (DHA, C22:6n-3), are well-known for their various health benefits, including cardiovascular and cognitive health. In this study we explored the EPA+DHA blood status across different states within the United States. A widely used marker to assess the EPA+DHA status is the omega-3 index – defined as the % of EPA+DHA in red blood cells (RBC) in relation to total fatty acids. A systematic literature search was conducted for US-studies from 2000 until October 2023 reporting EPA+DHA blood values. Further inclusion criteria were: information in which US state the study was carried out, no pregnant women, at least 16 years of age. A total of 46 studies met all inclusion criteria. EPA+DHA levels from studies utilizing blood metrics other than RBC were converted to an estimated RBC EPA+DHA (eRBC EPA+DHA) status marker using established conversion equations. The mean eRBC EPA+DHA across the US was 5.28% and, is in line with previous investigations. Most US states showed an average eRBC EPA+DHA in the range 4.50% to 5.50%. Furthermore, we found that coastal states tend to have higher eRBC EPA+DHA (5.26%) than inland states (4.86%). This is consistent with the slightly higher fish consumption in coastal states compared to inland states. The data from the studies included in the evaluation show that the blood status of EPA+DHA is suboptimal. The supply of EPA and DHA should be improved, especially in inland states. Further research is needed to better monitor EPA+DHA status in the US. Since the EPA+DHA blood status is a modifiable risk factor for many diseases, public health officials should take steps to emphasize the significance of n-3 PUFAs in preserving the health of the US population.
{"title":"Blood EPA and DHA status among people living in the United States from 2000 to 2023","authors":"Lea Gründler , Philine Beinhorn , Andreas Hahn , Jan Philipp Schuchardt","doi":"10.1016/j.plefa.2024.102653","DOIUrl":"10.1016/j.plefa.2024.102653","url":null,"abstract":"<div><div>Long-chain omega-3 polyunsaturated fatty acids (n-3 PUFAs), specifically eicosapentaenoic acid (EPA, C20:5n-3) and docosahexaenoic acid (DHA, C22:6n-3), are well-known for their various health benefits, including cardiovascular and cognitive health. In this study we explored the EPA+DHA blood status across different states within the United States. A widely used marker to assess the EPA+DHA status is the omega-3 index – defined as the % of EPA+DHA in red blood cells (RBC) in relation to total fatty acids. A systematic literature search was conducted for US-studies from 2000 until October 2023 reporting EPA+DHA blood values. Further inclusion criteria were: information in which US state the study was carried out, no pregnant women, at least 16 years of age. A total of 46 studies met all inclusion criteria. EPA+DHA levels from studies utilizing blood metrics other than RBC were converted to an estimated RBC EPA+DHA (eRBC EPA+DHA) status marker using established conversion equations. The mean eRBC EPA+DHA across the US was 5.28% and, is in line with previous investigations. Most US states showed an average eRBC EPA+DHA in the range 4.50% to 5.50%. Furthermore, we found that coastal states tend to have higher eRBC EPA+DHA (5.26%) than inland states (4.86%). This is consistent with the slightly higher fish consumption in coastal states compared to inland states. The data from the studies included in the evaluation show that the blood status of EPA+DHA is suboptimal. The supply of EPA and DHA should be improved, especially in inland states. Further research is needed to better monitor EPA+DHA status in the US. Since the EPA+DHA blood status is a modifiable risk factor for many diseases, public health officials should take steps to emphasize the significance of n-3 PUFAs in preserving the health of the US population.</div></div>","PeriodicalId":94179,"journal":{"name":"Prostaglandins, leukotrienes, and essential fatty acids","volume":"203 ","pages":"Article 102653"},"PeriodicalIF":3.0,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142515605","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-04-01DOI: 10.1016/j.plefa.2024.102654
Michael I. McBurney , Nathan L. Tintle , Jason Westra , William S. Harris , Sharon E. Curhan
Background
Disabling hearing loss affects ∼430 million people globally. Fish consumption and long-chain n-3 polyunsaturated fatty acid (PUFA) intake were inversely associated with risk of hearing loss, but the association of plasma n-3 PUFAs and hearing loss is unclear.
Objective
To examine the associations between plasma n-3 PUFA fractions (as % of total fatty acids), i.e., DHA % and Other n-3 PUFA % (defined as total n-3 PUFA minus DHA), with self-reported hearing difficulty in a population-based cohort in the UK.
Methods
Our study includes 175,177 UK Biobank participants (40–69y, 54 % women) with data on plasma n-3 PUFA and hearing status. Baseline plasma PUFA levels were analyzed by nuclear magnetic resonance, and self-reported hearing difficulty was obtained by questionnaire between 2007 and 2010. Logistic regression was used to estimate age-adjusted odds ratios (ORs), multivariable-adjusted odds ratios (MVORs) by adjusting for 14 demographic, behavioral, biomarker and health-related potential confounders, and 95 % confidence intervals (CIs).
Results
Hearing difficulty was reported by 26.7 % of participants. Higher plasma n-3 PUFA levels were independently associated with lower odds of self-reported hearing difficulty. The prevalence of hearing difficulty rose across age strata (40–49y, 15.8 %; 50–59y, 24.9 % and 60+y, 34.4 %; p < 0.0001) and overall was higher in males (33.2 %) than females (21.3 %). Compared with those in the lowest quintile of plasma DHA % or Other n-3 PUFA %, the MVOR (95 % CI) for hearing difficulty was 0.88 (0.85, 0.92) in highest quintile of plasma DHA %, and 0.91 (0.87, 0.94) in the highest quintile of Other n-3 PUFA %. The associations with DHA % did not differ by age or sex (p-for-interaction 0.83 and 0.58, respectively). MVORs for DHA % and Other n-3 PUFA % were similar among the 44,486 individuals with data on noise exposure at work.
Conclusions
Higher plasma n-3 PUFA levels were independently associated with lower odds of hearing difficulty.
{"title":"Cross-sectional analysis of plasma n-3 fatty acid levels and self-reported hearing difficulty in the UK Biobank Cohort","authors":"Michael I. McBurney , Nathan L. Tintle , Jason Westra , William S. Harris , Sharon E. Curhan","doi":"10.1016/j.plefa.2024.102654","DOIUrl":"10.1016/j.plefa.2024.102654","url":null,"abstract":"<div><h3>Background</h3><div>Disabling hearing loss affects ∼430 million people globally. Fish consumption and long-chain n-3 polyunsaturated fatty acid (PUFA) intake were inversely associated with risk of hearing loss, but the association of plasma n-3 PUFAs and hearing loss is unclear.</div></div><div><h3>Objective</h3><div>To examine the associations between plasma n-3 PUFA fractions (as % of total fatty acids), i.e., DHA % and Other n-3 PUFA % (defined as total n-3 PUFA minus DHA), with self-reported hearing difficulty in a population-based cohort in the UK.</div></div><div><h3>Methods</h3><div>Our study includes 175,177 UK Biobank participants (40–69y, 54 % women) with data on plasma n-3 PUFA and hearing status. Baseline plasma PUFA levels were analyzed by nuclear magnetic resonance, and self-reported hearing difficulty was obtained by questionnaire between 2007 and 2010. Logistic regression was used to estimate age-adjusted odds ratios (ORs), multivariable-adjusted odds ratios (MVORs) by adjusting for 14 demographic, behavioral, biomarker and health-related potential confounders, and 95 % confidence intervals (CIs).</div></div><div><h3>Results</h3><div>Hearing difficulty was reported by 26.7 % of participants. Higher plasma n-3 PUFA levels were independently associated with lower odds of self-reported hearing difficulty. The prevalence of hearing difficulty rose across age strata (40–49y, 15.8 %; 50–59y, 24.9 % and 60+<em>y</em>, 34.4 %; <em>p</em> < 0.0001) and overall was higher in males (33.2 %) than females (21.3 %). Compared with those in the lowest quintile of plasma DHA % or Other n-3 PUFA %, the MVOR (95 % CI) for hearing difficulty was 0.88 (0.85, 0.92) in highest quintile of plasma DHA %, and 0.91 (0.87, 0.94) in the highest quintile of Other n-3 PUFA %. The associations with DHA % did not differ by age or sex (p-for-interaction 0.83 and 0.58, respectively). MVORs for DHA % and Other n-3 PUFA % were similar among the 44,486 individuals with data on noise exposure at work.</div></div><div><h3>Conclusions</h3><div>Higher plasma n-3 PUFA levels were independently associated with lower odds of hearing difficulty.</div></div>","PeriodicalId":94179,"journal":{"name":"Prostaglandins, leukotrienes, and essential fatty acids","volume":"203 ","pages":"Article 102654"},"PeriodicalIF":3.0,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142587433","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}
Gallein, a small molecule related to fluorescein, is established as an inhibitor of Gβγ subunits to inhibit G protein (Gs) signaling. This agent is providing a potential therapeutic strategy to ameliorate organ dysfunctions especially involved in inflammation, however; the effects on bone metabolism have not yet been clarified. Prostaglandins (PGs) play important roles as autacoids including osteoblasts, and d-type prostanoid (DP) receptor, a member of G protein-coupled receptor specific to PGD2, is expressed on osteoblasts. We previously reported that prostaglandin D2 (PGD2) induces the syntheses of osteoprotegerin (OPG) and interleukin-6 (IL-6), essential factors in bone remodelling process, and p38 mitogen-activated protein kinase (MAPK), c-Jun N-terminal kinase (JNK), and p44/p42 MAPK are involved in the signal transduction of PGD2 in osteoblast-like MC3T3-E1 cells. Thus, we investigated in this study that the effect and the underlying mechanism of gallein, an inhibitor Gβɤ subunits, on the syntheses of OPG and IL-6 induced by PGD2 in these cells. The cultured cells were treated with gallein or fluorescein, a structurally related compound inactive to Gβɤ subunits, and subsequently stimulated with PGD2. Not fluorescein but gallein amplified the PGD2-stimulated releases of OPG and IL-6. Gallein enhanced the PGD2-upregulated mRNA expression levels of OPG and IL-6. Regarding the signaling mechanism, gallein did not affect the PGD2-induced phosphorylation of p38 MAPK, JNK, or p42 MAPK. In conclusion, gallein upregulates the PGD2-stimulated syntheses of OPG and IL-6 by the specific effect to inhibit Gβγ subunits in osteoblasts, but the effect is not exerted at the upstream of p38 MAPK, JNK, or p44/p42 MAPK activation.
{"title":"Gallein but not fluorescein enhances the PGD2-stimulated synthesis of osteoprotegerin and interleukin-6 in osteoblasts","authors":"Tomoyuki Hioki , Gen Kuroyanagi , Rie Matsushima-Nishiwaki , Takuya Omura , Osamu Kozawa , Haruhiko Tokuda","doi":"10.1016/j.plefa.2024.102639","DOIUrl":"10.1016/j.plefa.2024.102639","url":null,"abstract":"<div><p>Gallein, a small molecule related to fluorescein, is established as an inhibitor of Gβγ subunits to inhibit G protein (Gs) signaling. This agent is providing a potential therapeutic strategy to ameliorate organ dysfunctions especially involved in inflammation, however; the effects on bone metabolism have not yet been clarified. Prostaglandins (PGs) play important roles as autacoids including osteoblasts, and <span>d</span>-type prostanoid (DP) receptor, a member of G protein-coupled receptor specific to PGD<sub>2</sub>, is expressed on osteoblasts. We previously reported that prostaglandin D<sub>2</sub> (PGD<sub>2</sub>) induces the syntheses of osteoprotegerin (OPG) and interleukin-6 (IL-6), essential factors in bone remodelling process, and p38 mitogen-activated protein kinase (MAPK), c-<em>Jun</em> N-terminal kinase (JNK), and p44/p42 MAPK are involved in the signal transduction of PGD<sub>2</sub> in osteoblast-like MC3T3-E1 cells. Thus, we investigated in this study that the effect and the underlying mechanism of gallein, an inhibitor Gβɤ subunits, on the syntheses of OPG and IL-6 induced by PGD<sub>2</sub> in these cells. The cultured cells were treated with gallein or fluorescein, a structurally related compound inactive to Gβɤ subunits, and subsequently stimulated with PGD<sub>2</sub>. Not fluorescein but gallein amplified the PGD<sub>2</sub>-stimulated releases of OPG and IL-6. Gallein enhanced the PGD<sub>2</sub>-upregulated mRNA expression levels of OPG and IL-6. Regarding the signaling mechanism, gallein did not affect the PGD<sub>2</sub>-induced phosphorylation of p38 MAPK, JNK, or p42 MAPK. In conclusion, gallein upregulates the PGD<sub>2</sub>-stimulated syntheses of OPG and IL-6 by the specific effect to inhibit Gβγ subunits in osteoblasts, but the effect is not exerted at the upstream of p38 MAPK, JNK, or p44/p42 MAPK activation.</p></div>","PeriodicalId":94179,"journal":{"name":"Prostaglandins, leukotrienes, and essential fatty acids","volume":"203 ","pages":"Article 102639"},"PeriodicalIF":3.0,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142172596","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 : 2024-04-01DOI: 10.1016/j.plefa.2024.102643
Zhenglong Chai , Hui Zhang , Xinyue Ji , Xinyi Hu , Yannan He , Feng Zhao , Chunyan Song , Yiqiu Zhou , Tao Li , Canxia He , Dezheng Zhou , Xiaohong Zhang
The health benefits of omega-3 polyunsaturated fatty acids (omega-3 PUFAs), primarily eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), are linked to their regulatory effects on the composition of the gut microbiota. However, there is a lack of direct evidence on whether omega-3 PUFAs regulate the gut microbial homeostasis under physiological conditions. This study investigated the impact of equivalent doses of EPA, DHA, and fish oil (FO) with a DHA to EPA ratio of approximately 1:1 on the bacterial and fungal composition of normal young mice. This study also analyzed changes in key components of the gut microenvironment, including the colonic mucus barrier and short-chain fatty acids, to address the prebiotic potential of omega-3 PUFAs. The results showed that all three omega-3 PUFAs interventions induced significant fluctuations in the gut bacteria and fungi, leading to an increase in the abundance of some probiotics. Notably, DHA, EPA, and FO interventions significantly increased the abundance of the probiotic Lactobacillus, Bifidobacterium, and Akkermansia, respectively. Both DHA and fish oil interventions also significantly reduced the abundance of potentially pathogenic fungi, such as Aspergillus and Penicillium. Association analysis of the top 19 differential fungal and bacterial genera in abundance revealed a much more bacteria-bacteria and bacteria-fungi connections, but fewer fungi-fungi connections. This highlights the importance of bacteria in the gut microecological network. Furthermore, the levels of butyric acid and valeric acid in the colonic contents of DHA intervention group were significantly increased, and the colonic mucus layer thickness was increased in three treatment groups. In summary, DHA, EPA and FO interventions showed targeted enhancement of different probiotics and enhanced colon defense barrier (mucus barrier), showing potential prebiotic effects.
{"title":"The disparate effects of omega-3 PUFAs on intestinal microbial homeostasis in experimental rodents under physiological condition","authors":"Zhenglong Chai , Hui Zhang , Xinyue Ji , Xinyi Hu , Yannan He , Feng Zhao , Chunyan Song , Yiqiu Zhou , Tao Li , Canxia He , Dezheng Zhou , Xiaohong Zhang","doi":"10.1016/j.plefa.2024.102643","DOIUrl":"10.1016/j.plefa.2024.102643","url":null,"abstract":"<div><div>The health benefits of omega-3 polyunsaturated fatty acids (omega-3 PUFAs), primarily eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), are linked to their regulatory effects on the composition of the gut microbiota. However, there is a lack of direct evidence on whether omega-3 PUFAs regulate the gut microbial homeostasis under physiological conditions. This study investigated the impact of equivalent doses of EPA, DHA, and fish oil (FO) with a DHA to EPA ratio of approximately 1:1 on the bacterial and fungal composition of normal young mice. This study also analyzed changes in key components of the gut microenvironment, including the colonic mucus barrier and short-chain fatty acids, to address the prebiotic potential of omega-3 PUFAs. The results showed that all three omega-3 PUFAs interventions induced significant fluctuations in the gut bacteria and fungi, leading to an increase in the abundance of some probiotics. Notably, DHA, EPA, and FO interventions significantly increased the abundance of the probiotic <em>Lactobacillus, Bifidobacterium</em>, and <em>Akkermansia</em>, respectively. Both DHA and fish oil interventions also significantly reduced the abundance of potentially pathogenic fungi, such as <em>Aspergillus</em> and <em>Penicillium</em>. Association analysis of the top 19 differential fungal and bacterial genera in abundance revealed a much more bacteria-bacteria and bacteria-fungi connections, but fewer fungi-fungi connections. This highlights the importance of bacteria in the gut microecological network. Furthermore, the levels of butyric acid and valeric acid in the colonic contents of DHA intervention group were significantly increased, and the colonic mucus layer thickness was increased in three treatment groups. In summary, DHA, EPA and FO interventions showed targeted enhancement of different probiotics and enhanced colon defense barrier (mucus barrier), showing potential prebiotic effects.</div></div>","PeriodicalId":94179,"journal":{"name":"Prostaglandins, leukotrienes, and essential fatty acids","volume":"203 ","pages":"Article 102643"},"PeriodicalIF":3.0,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142311051","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}
Acute respiratory distress syndrome (ARDS) is a life-threatening condition involving severe lung inflammation. The excessive oxidative stress and persistent inflammation that occur in ARDS lead to decreased epithelial integrity and hypoxemia due to pulmonary edema via increased vascular permeability. Resolvin D4 (RvD4) is one of the lipid mediators that is biosynthesized from omega-3 polyunsaturated fatty acids. It plays a role in the resolution of inflammation and reduces oxidative stress and cell death. We investigated the therapeutic potential of the administration of RvD4 in a murine model of lipopolysaccharide (LPS)-induced ARDS. Concurrent with the intratracheal administration of LPS, RvD4 or saline was administered to mice via the caudal vein every 12 h. This treatment with RvD4 alleviated the LPS-induced infiltration of inflammatory cells in lungs, inhibited increased pulmonary vascular permeability, decreased the levels of IL-1β, IL-6, and TNF-α in bronchoalveolar lavage fluid (BALF), and suppressed the reduction of the expression levels of the tight junction protein, Zonula occludens-1 (Zo-1) and the NAD+-dependent deacetylase, Sirtuin-3 (Sirt3). In vitro experiments revealed that in LPS-stimulated BEAS-2B cells, treatment with RvD4 suppressed the increases in the expressions of pro-inflammatory cytokines and maintained the epithelial cell barrier function and cell viability. The silencing of SIRT3 abolished both the anti-inflammatory effect and the retention of cell integrity in BEAS-2B cells. Together these results indicate that treatment with RvD4 can (i) protect against LPS-induced lung injury by inhibiting inflammation, and (ii) maintain epithelial barrier function via a reduction in the downregulation of SIRT3.
{"title":"Resolvin D4 mitigates lipopolysaccharide-induced lung injury in mice","authors":"Rika Inomata , Hironobu Tsubouchi , Toshifumi Takao , Mone Kurokawa , Shigehisa Yanagi , Katsuya Sakai , Taiga Miyazaki","doi":"10.1016/j.plefa.2024.102652","DOIUrl":"10.1016/j.plefa.2024.102652","url":null,"abstract":"<div><div>Acute respiratory distress syndrome (ARDS) is a life-threatening condition involving severe lung inflammation. The excessive oxidative stress and persistent inflammation that occur in ARDS lead to decreased epithelial integrity and hypoxemia due to pulmonary edema via increased vascular permeability. Resolvin D4 (RvD4) is one of the lipid mediators that is biosynthesized from omega-3 polyunsaturated fatty acids. It plays a role in the resolution of inflammation and reduces oxidative stress and cell death. We investigated the therapeutic potential of the administration of RvD4 in a murine model of lipopolysaccharide (LPS)-induced ARDS. Concurrent with the intratracheal administration of LPS, RvD4 or saline was administered to mice via the caudal vein every 12 h. This treatment with RvD4 alleviated the LPS-induced infiltration of inflammatory cells in lungs, inhibited increased pulmonary vascular permeability, decreased the levels of IL-1β, IL-6, and TNF-α in bronchoalveolar lavage fluid (BALF), and suppressed the reduction of the expression levels of the tight junction protein, Zonula occludens-1 (Zo-1) and the NAD+-dependent deacetylase, Sirtuin-3 (Sirt3). In vitro experiments revealed that in LPS-stimulated BEAS-2B cells, treatment with RvD4 suppressed the increases in the expressions of pro-inflammatory cytokines and maintained the epithelial cell barrier function and cell viability. The silencing of <em>SIRT3</em> abolished both the anti-inflammatory effect and the retention of cell integrity in BEAS-2B cells. Together these results indicate that treatment with RvD4 can (<em>i</em>) protect against LPS-induced lung injury by inhibiting inflammation, and (<em>ii</em>) maintain epithelial barrier function via a reduction in the downregulation of SIRT3.</div></div>","PeriodicalId":94179,"journal":{"name":"Prostaglandins, leukotrienes, and essential fatty acids","volume":"203 ","pages":"Article 102652"},"PeriodicalIF":3.0,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142378749","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Mice fed a diet containing an adequate amount of ω-3 fatty acids (ω-3 Adq) or a deficient diet (ω-3 Def) were irradiated with ultraviolet-B (UV-B) and were measured daily changes in transepidermal water loss (TEWL). TEWL was significantly increased in ω-3 Def mice with repeated UV-B irradiation, but this increase was significantly reduced in ω-3 Adq mice. The epidermal layers revealed thickening of the spinous and basal layers induced by UV-B irradiation in both groups. Moreover, the ω-3 Def mice had a disturbed epidermal structure and a coarser stratum corneum. And the granule cell layer is significantly reduced, and abnormal layer formation (parakeratosis) occurred in the stratum corneum. These results suggest that continuous UV-B irradiation promotes epidermal turnover and leads to epidermal thickening, but ω-3 fatty acids protect the body from UV-B-induced stress.
{"title":"Omega-3 fatty acids mitigate skin damage caused by ultraviolet-B radiation","authors":"Akiko Harauma , Yui Enomoto , Sayaka Endo , Himeka Hariya , Toru Moriguchi","doi":"10.1016/j.plefa.2024.102641","DOIUrl":"10.1016/j.plefa.2024.102641","url":null,"abstract":"<div><p>Mice fed a diet containing an adequate amount of ω-3 fatty acids (ω-3 Adq) or a deficient diet (ω-3 Def) were irradiated with ultraviolet-B (UV-B) and were measured daily changes in transepidermal water loss (TEWL). TEWL was significantly increased in ω-3 Def mice with repeated UV-B irradiation, but this increase was significantly reduced in ω-3 Adq mice. The epidermal layers revealed thickening of the spinous and basal layers induced by UV-B irradiation in both groups. Moreover, the ω-3 Def mice had a disturbed epidermal structure and a coarser stratum corneum. And the granule cell layer is significantly reduced, and abnormal layer formation (parakeratosis) occurred in the stratum corneum. These results suggest that continuous UV-B irradiation promotes epidermal turnover and leads to epidermal thickening, but ω-3 fatty acids protect the body from UV-B-induced stress.</p></div>","PeriodicalId":94179,"journal":{"name":"Prostaglandins, leukotrienes, and essential fatty acids","volume":"203 ","pages":"Article 102641"},"PeriodicalIF":3.0,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0952327824000358/pdfft?md5=c3429b485f7e0c2196629fd7f048d66d&pid=1-s2.0-S0952327824000358-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142238087","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-03-01DOI: 10.1016/j.plefa.2024.102627
Elisabetta Di Profio , Patrizia Risé , Lara Orlandi , Elena Zoia , Christian Pinna , Angelo Sala , Gianvincenzo Zuccotti , Elvira Verduci
The growing interest in Omega-3 fatty acids as diagnostic markers or new therapeutic approaches also for COVID-19 disease, led us to investigate the presence of potential correlations between Omega-3 fatty acids’ levels in whole blood and days of hospitalization or admission to the paediatric intensive care unit (PICU) in 51 children with MIS-C diagnosis following SARS-CoV-2 infection. A statistically significant negative correlation was observed between days of hospitalization and docosapentaenoic acid (22:5n-3,DPA), docosahexaenoic acid (DHA) and total Omega-3 FA levels. Dividing the study group into quartiles according to Omega-3-Index (O3I), no statistically significant difference was observed with respect to the PICU admission rate. In contrast, the number of days of hospitalization in Q4 (O3I ≥ 2.51 %) was different from the number observed in groups Q1-3 (O3I < 2.51 %), with subjects showing higher O3I needing shorter hospitalizations than the subjects with lower O3I. According to previous study investigating O3I in adults affected by Sars-cov-2 we explored the levels of this nutrients in children with MIS-C. Our exploratory study shows that high DPA, DHA and O3I levels could be effective in reducing the length of hospitalization.
{"title":"Unsaturated fatty acids, omega-3 index and hospitalization in MISC","authors":"Elisabetta Di Profio , Patrizia Risé , Lara Orlandi , Elena Zoia , Christian Pinna , Angelo Sala , Gianvincenzo Zuccotti , Elvira Verduci","doi":"10.1016/j.plefa.2024.102627","DOIUrl":"10.1016/j.plefa.2024.102627","url":null,"abstract":"<div><p>The growing interest in Omega-3 fatty acids as diagnostic markers or new therapeutic approaches also for COVID-19 disease, led us to investigate the presence of potential correlations between Omega-3 fatty acids’ levels in whole blood and days of hospitalization or admission to the paediatric intensive care unit (PICU) in 51 children with MIS-C diagnosis following SARS-CoV-2 infection. A statistically significant negative correlation was observed between days of hospitalization and docosapentaenoic acid (22:5n-3,DPA), docosahexaenoic acid (DHA) and total Omega-3 FA levels. Dividing the study group into quartiles according to Omega-3-Index (O3I), no statistically significant difference was observed with respect to the PICU admission rate. In contrast, the number of days of hospitalization in Q4 (O3I ≥ 2.51 %) was different from the number observed in groups Q1-3 (O3I < 2.51 %), with subjects showing higher O3I needing shorter hospitalizations than the subjects with lower O3I. According to previous study investigating O3I in adults affected by Sars-cov-2 we explored the levels of this nutrients in children with MIS-C. Our exploratory study shows that high DPA, DHA and O3I levels could be effective in reducing the length of hospitalization.</p></div>","PeriodicalId":94179,"journal":{"name":"Prostaglandins, leukotrienes, and essential fatty acids","volume":"202 ","pages":"Article 102627"},"PeriodicalIF":3.0,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141536293","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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