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Keywords = DHA-PC

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15 pages, 3968 KiB  
Article
Brain Pericytes Enhance MFSD2A Expression and Plasma Membrane Localization in Brain Endothelial Cells Through the PDGF-BB/PDGFRβ Signaling Pathway
by Takuro Iwao, Fuyuko Takata, Hisataka Aridome, Miho Yasunaga, Miki Yokoya, Junko Mizoguchi and Shinya Dohgu
Int. J. Mol. Sci. 2025, 26(13), 5949; https://doi.org/10.3390/ijms26135949 - 20 Jun 2025
Viewed by 399
Abstract
The brain actively obtains nutrients through various transporters on brain microvessel endothelial cells (BMECs). Major facilitator superfamily domain–containing protein 2a (MFSD2A) serves as a key transporter of docosahexaenoic acid (DHA) at the blood–brain barrier (BBB) and is exclusively expressed in BMECs. Although brain [...] Read more.
The brain actively obtains nutrients through various transporters on brain microvessel endothelial cells (BMECs). Major facilitator superfamily domain–containing protein 2a (MFSD2A) serves as a key transporter of docosahexaenoic acid (DHA) at the blood–brain barrier (BBB) and is exclusively expressed in BMECs. Although brain pericytes (PCs) regulate MFSD2A expression in BMECs, the underlying mechanism remains unclear. To determine whether PDGF-BB/PDGFRβ signaling between endothelial cells (ECs) and PCs affects MFSD2A protein expression and plasma membrane localization in ECs, we examined the impact of AG1296 (a PDGF receptor inhibitor) and Pdgfrb-knockdown PCs on a non-contact coculture BBB model comprising the primary cultures of rat brain ECs and PCs. The effects of PCs on MFSD2A expression, localization, and brain endothelial DHA uptake was assessed using Western blot, immunofluorescence staining, and [14C]DHA uptake by ECs, respectively. In ECs cocultured with PCs, MFSD2A expression and plasma membrane localization were significantly higher than in EC monolayers. Moreover, conditioned medium derived from PCs failed to enhance MFSD2A expression. The increased expression and membrane localization of MFSD2A were inhibited by AG1296 and Pdgfrb-knockdown PCs. Furthermore, PCs significantly increased [14C]DHA uptake by ECs. These findings suggest that PCs enhance MFSD2A expression and plasma membrane localization in ECs through PDGF-BB/PDGFRβ signaling. Full article
(This article belongs to the Collection Feature Papers in Molecular Neurobiology)
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16 pages, 1293 KiB  
Article
Comprehensive Characterization of Serum Lipids of Dairy Cows: Effects of Negative Energy Balance on Lipid Remodelling
by Zhiqian Liu, Wenjiao Wang, Joanne E. Hemsworth, Coralie M. Reich, Carolyn R. Bath, Monique J. Berkhout, Muhammad S. Tahir, Vilnis Ezernieks, Leah C. Marett, Amanda J. Chamberlain, Mike E. Goddard and Simone J. Rochfort
Metabolites 2025, 15(4), 274; https://doi.org/10.3390/metabo15040274 - 15 Apr 2025
Viewed by 610
Abstract
Background: The presence and concentration of lipids in serum of dairy cows have significant implications for both animal health and productivity and are potential biomarkers for several common diseases. However, information on serum lipid composition is rather fragmented, and lipid remodelling during the [...] Read more.
Background: The presence and concentration of lipids in serum of dairy cows have significant implications for both animal health and productivity and are potential biomarkers for several common diseases. However, information on serum lipid composition is rather fragmented, and lipid remodelling during the transition period is only partially understood. Methods: Using a combination of reversed-phase liquid chromatography-mass spectrometry (RP-LC-MS), hydrophilic interaction-mass spectrometry (HILIC-MS), and lipid annotation software, we performed a comprehensive identification and quantification of serum of dairy cows in pasture-based Holstein-Friesian cows. The lipid remodelling induced by negative energy balance was investigated by comparing the levels of all identified lipids between the fresh lactation (5–14 days in milk, DIM) and full lactation (65–80 DIM) stages. Results: We identified 535 lipid molecular species belonging to 19 classes. The most abundant lipid class was cholesteryl ester (CE), followed by phosphatidylcholine (PC), sphingomyelin (SM), and free fatty acid (FFA), whereas the least abundant lipids included phosphatidylserine (PS), phosphatidic acid (PA), phosphatidylglycerol (PG), acylcarnitine (AcylCar), ceramide (Cer), glucosylceramide (GluCer), and lactosylceramide (LacCer). Conclusions: A remarkable increase in most lipids and a dramatic decrease in FFAs, AcylCar, and DHA-containing species were observed at the full lactation compared to fresh lactation stage. Several serum lipid biomarkers for detecting negative energy balance in cows were also identified. Full article
(This article belongs to the Special Issue Effects of Stress on Animal Metabolism)
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22 pages, 12534 KiB  
Article
A Multi-Omics Study of Neurodamage Induced by Growth-Stage Real-Time Air Pollution Exposure in Mice via the Microbiome–Gut–Brain Axis
by Zijun Yang, Yi Zhang, Shanshan Ran, Jingyi Zhang, Fei Tian, Hui Shi, Shengtao Wei, Xiuxiu Li, Xinyue Li, Yonggui Gao, Guang Jia, Hualiang Lin, Zhangjian Chen and Zilong Zhang
Toxics 2025, 13(4), 260; https://doi.org/10.3390/toxics13040260 - 29 Mar 2025
Viewed by 768
Abstract
Air pollution has been widely recognized as a risk factor for neurological disorders, and the gut microbiome may play a mediating role. However, current evidence remains limited. In this study, a mouse model was employed with continuous exposure to real-time air pollution from [...] Read more.
Air pollution has been widely recognized as a risk factor for neurological disorders, and the gut microbiome may play a mediating role. However, current evidence remains limited. In this study, a mouse model was employed with continuous exposure to real-time air pollution from conception to late adolescence. Effects of growth-stage air pollution exposure on the gut microbiome, host metabolites, and brain tissue were assessed. Pathological damage in the hippocampus and cortex was observed. Fecal metagenomic sequencing revealed alterations in both compositions and functions of the gut microbiome. Metabolic disturbances in unsaturated fatty acids and glycerophospholipids were identified in the intestine, serum, and brain tissues, with significant changes in metabolites (e.g., gamma-linolenic acid, alpha-linolenic acid, docosahexaenoic acid (DHA), phosphatidylethanolamine (PE), phosphatidylcholine (PC) and phosphatidylserine (PS). Serum levels of the pro-inflammatory mediator leukotriene C4 were also elevated. Correlation analysis identified a group of different gut microbiome species that were associated with host metabolites. Furthermore, mediation analysis showed that intestinal and serum metabolites mediated the associations between the key gut microbiome and brain microbiome. These findings indicate that the metabolic crosstalk in the gut–brain axis mediates the neuronal damage in mice induced by growth-stage air pollution exposure, potentially through pathways involving lipid metabolism and inflammation. Full article
(This article belongs to the Special Issue Health Effects of Exposure to Environmental Pollutants)
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16 pages, 2189 KiB  
Article
Enzymatic Synthesis of Bioactive Structured DHA Phospholipids via Stable Immobilized Phospholipase-Catalyzed Esterification in a Solvent-Free Medium
by Ernestina Garcia-Quinto, Jose M. Guisan and Gloria Fernandez-Lorente
Processes 2025, 13(2), 442; https://doi.org/10.3390/pr13020442 - 6 Feb 2025
Cited by 1 | Viewed by 1212
Abstract
The enzymatic esterification of docosahexaenoic acid (DHA) with glycerophosphocholine (GPC) was investigated to produce bioactive structured DHA phospholipids with DHA esterified at the sn-2 position, which may contribute to the prevention of neurodegenerative diseases such as Alzheimer’s. This reaction is complex due to [...] Read more.
The enzymatic esterification of docosahexaenoic acid (DHA) with glycerophosphocholine (GPC) was investigated to produce bioactive structured DHA phospholipids with DHA esterified at the sn-2 position, which may contribute to the prevention of neurodegenerative diseases such as Alzheimer’s. This reaction is complex due to the low solubility of GPC in anhydrous organic media and the limited stability of enzymes under such conditions. The immobilized phospholipase Quara® LowP (QlowP-C18) proved to be the most effective catalyst, achieving a 58% yield of di-substituted DHA phospholipids (Di-DHA-PC) in just 48 h under optimal conditions (solvent-free media at 60 °C) with 95% purity. Advanced immobilization and post-immobilization techniques significantly improved the stability of QlowP-C18, increasing its longevity threefold and enabling reuse for up to five reaction cycles at 40 °C. The total production reached 120.4 mg of highly pure DHA-di-substituted phospholipid. These findings highlight the effectiveness of stable immobilized enzymes in solvent-free systems and underscore their potential for the efficient and sustainable production of highly pure Di-DHA-PC, which could be used as a functional or nutraceutical ingredient for the prevention of neurodegenerative diseases. Full article
(This article belongs to the Section Food Process Engineering)
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19 pages, 3209 KiB  
Article
Lipidomics Analysis Reveals the Effects of Docosahexaenoic Acid from Different Sources on Prefrontal-Cortex Synaptic Plasticity
by Zude He, Wei Xiong, Yue Yang, Yifan Zhang, Boying Li, Fuqing Wang, Yixuan Li, Ran Wang and Yanan Sun
Nutrients 2025, 17(3), 457; https://doi.org/10.3390/nu17030457 - 27 Jan 2025
Viewed by 1726
Abstract
Background: Docosahexaenoic Acid (DHA) is an extensively used nutrition supplement in dairy food because of its beneficial effects on cognition. To find an effective DHA intervention for the synapses in the cortex during this period, this study aimed to use targeted lipidomics to [...] Read more.
Background: Docosahexaenoic Acid (DHA) is an extensively used nutrition supplement in dairy food because of its beneficial effects on cognition. To find an effective DHA intervention for the synapses in the cortex during this period, this study aimed to use targeted lipidomics to evaluate the lipid composition of prefrontal-cortex (PFC) tissue in different DHA interference methods. Methods: Analyzed samples were taken from interfering feeding Bama pigs (BPs) (3 months) fed with soybean oil (Group B), blended oil (Group M), naturally DHA-supplemented milk with blended oil (Group OM), and DHA from fish oil (FO) with blended oil (Group Y). We also examined the protein expression levels of BDNF, GAP43, and MBP. Results: The lipidomics analysis identified 80 different related negative-ion lipid content and filtered the biomarker lipids in PFC tissue. We observed significant lipid composition changes between group Y and other groups, especially for content levels of phosphatidylcholine (PC), phosphatidylethanolamine (PE), phosphatidylinositol (PI), phosphatidylserine (PS), and sphingomyelin (SM). The same observations were made from mRNA and protein expressions related to lipid transportation, phosphatidylserine (PS) synthetase, and synaptic plasticity in PFC tissues between group Y and other groups, including the mRNA expression levels of CD36, BDNF, and PTDSS1. The analysis of protein expression levels showed that the metabolism mode of DHA intervention from FO benefited the PFC, PS metabolism, and PFC synaptic plasticity of infants. Conclusions: The results highlight further prospects for the DHA intervention mode, which provides new routes for other studies on polyunsaturated-fatty-acid (PUFA) interference for infants. Full article
(This article belongs to the Special Issue Nutrition Interventions and Their Impact on Brain Health and Disease)
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16 pages, 10924 KiB  
Article
Building of CuO2@Cu-TA@DSF/DHA Nanoparticle Targets MAPK Pathway to Achieve Synergetic Chemotherapy and Chemodynamic for Pancreatic Cancer Cells
by Jiaru Zhang, Zuoping Li, Zhenzhen Xie, Shiwan You, Yanbing Chen, Yuling Zhang, Jing Zhang, Na Zhao, Xiling Deng and Shiguo Sun
Pharmaceutics 2024, 16(12), 1614; https://doi.org/10.3390/pharmaceutics16121614 - 19 Dec 2024
Cited by 1 | Viewed by 1247
Abstract
Background/Objectives: With the increase of reactive oxygen species (ROS) production, cancer cells can avoid cell death and damage by up-regulating antioxidant programs. Therefore, it will be more effective to induce cell death by using targeted strategies to further improve ROS levels and drugs [...] Read more.
Background/Objectives: With the increase of reactive oxygen species (ROS) production, cancer cells can avoid cell death and damage by up-regulating antioxidant programs. Therefore, it will be more effective to induce cell death by using targeted strategies to further improve ROS levels and drugs that inhibit antioxidant programs. Methods: Considering that dihydroartemisinin (DHA) can cause oxidative damage to protein, DNA, or lipids by producing excessive ROS, while, disulfiram (DSF) can inhibit glutathione (GSH) levels and achieve the therapeutic effect by inhibiting antioxidant system and amplifying oxidative stress, they were co-loaded onto the copper peroxide nanoparticles (CuO2) coated with copper tannic acid (Cu-TA), to build a drug delivery system of CuO2@Cu-TA@DSF/DHA nanoparticles (CCTDD NPs). In response to the tumor microenvironment, DHA interacts with copper ion (Cu2+) to produce ROS, and a double (diethylthiocarbamate)-copper (II) (CuET) is generated by the complexation of DSF and Cu2+, which consumes GSH and inhibits antioxidant system. Meanwhile, utilizing the Fenton-like effect induced by the multi-copper mode can achieve ROS storm, activate the MAPK pathway, and achieve chemotherapy (CT) and chemodynamic (CDT). Results: Taking pancreatic cancer cell lines PANC-1 and BxPC-3 as the research objects, cell line experiments in vitro proved that CCTDD NPs exhibit efficient cytotoxicity on cancer cells. Conclusions: The CCTDD NPs show great potential in resisting pancreatic cancer cells and provides a simple strategy for designing powerful metal matrix composites. Full article
(This article belongs to the Special Issue Biocompatible Polymers for Drug Delivery)
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19 pages, 2606 KiB  
Article
Pro-Resolving Inflammatory Effects of a Marine Oil Enriched in Specialized Pro-Resolving Mediators (SPMs) Supplement and Its Implication in Patients with Post-COVID Syndrome (PCS)
by Asun Gracia Aznar, Fernando Moreno Egea, Rafael Gracia Banzo, Rocio Gutierrez, Jose Miguel Rizo, Pilar Rodriguez-Ledo, Isabel Nerin and Pedro-Antonio Regidor
Biomedicines 2024, 12(10), 2221; https://doi.org/10.3390/biomedicines12102221 - 29 Sep 2024
Cited by 4 | Viewed by 1836
Abstract
Objectives: This study aimed to evaluate the eicosanoid and pro-resolutive parameters in patients with Post-COVID Syndrome (PCS) during a 12-week supplementation with a marine oil enriched in specialized pro-resolving mediators (SPMs). Patient and methods: This study was conducted on 53 adult patients with [...] Read more.
Objectives: This study aimed to evaluate the eicosanoid and pro-resolutive parameters in patients with Post-COVID Syndrome (PCS) during a 12-week supplementation with a marine oil enriched in specialized pro-resolving mediators (SPMs). Patient and methods: This study was conducted on 53 adult patients with PCS. The subjects included must have had a positive COVID-19 test (PCR, fast antigen test, or serologic test) and persistent symptoms related to COVID-19 at least 12 weeks before their enrolment in the study. The following parameters were evaluated: polyunsaturated fatty acids EPA, DHA, ARA, and DPA; specialized pro-resolving mediators (SPMs), 17-HDHA, 18-HEPE, 14-HDHA, resolvins, maresins, protectins, and lipoxins. The eicosanoids group included prostaglandins, thromboxanes, and leukotrienes. The development of the clinical symptoms of fatigue and dyspnea were evaluated using the Fatigue Severity Scale (FSS) and the Modified Medical Research Council (mMRC) Dyspnea Scale. Three groups with different intake amounts were evaluated (daily use of 500 mg, 1500 mg, and 3000 mg) and compared to a control group not using the product. Results: In the serum from patients with PCS, an increase in 17-HDHA, 18-HEPE, and 14-HDHA could be observed, and a decrease in the ratio between the pro-inflammatory and pro-resolutive lipid mediators was detected; both differences were significant (p < 0.05). There were no differences found between the three treatment groups. Fatigue and dyspnea showed a trend of improvement after supplementation in all groups. Conclusions: A clear enrichment in the serum of the three monohydroxylated SPMs could be observed at a dosage of 500 mg per day. Similarly, a clear improvement in fatigue and dyspnea was observed with this dosage. Full article
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17 pages, 5615 KiB  
Article
Sex-Specific Lipid Profiles and Flavor Volatiles in Giant Salamander (Andrias davidianus) Tails Revealed by Lipidomics and GC-IMS
by Shibo Zhao, Jinghong Yu, Linjie Xi, Xiangdong Kong, Jinjin Pei, Pengfei Jiang, Ruichang Gao and Wengang Jin
Foods 2024, 13(19), 3048; https://doi.org/10.3390/foods13193048 - 25 Sep 2024
Cited by 3 | Viewed by 1500
Abstract
To elucidate the relationships between lipid components and odor traits, this study comparatively characterized the distinct lipid compositions and flavor volatiles in giant salamander tails of different sexes via mass-spectrometry-based lipidomics and GC-IMS. A total of 3145 fat metabolites were detected in male [...] Read more.
To elucidate the relationships between lipid components and odor traits, this study comparatively characterized the distinct lipid compositions and flavor volatiles in giant salamander tails of different sexes via mass-spectrometry-based lipidomics and GC-IMS. A total of 3145 fat metabolites were detected in male and female giant salamander tails, with the largest contributors being triglycerides (TGs, 840) and phosphatidylcholines (PCs, 383). Notably, the contents of PCs and TGs were greater in female tails than in male tails, and the levels of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) were also greater in the female group. Additionally, a total of 45 volatile components were detected, namely, 14 aldehydes, 14 alcohols, 9 ketones, 3 acids, 3 esters, 1 ether, and 1 amine. Alcohols (29.96% to 34.85%) and aldehydes (21.07% to 22.75%) were the predominant volatiles. Multivariate statistical analysis revealed 22 key differential fats and 26 differential odor substances as distinguishing labels between sexes. Correlation analysis revealed that the concentrations of triethylamine, dimethyl sulfide, ethanol-D, and 3-methyl butanal-D were significantly positively correlated with the concentrations of diglyceride (DG) (26:6e), cardiolipin (CL) (59:4), acylcarnitine (AcCa) (22:4), and triglyceride (TG) (52:10) (p < 0.01). Threefold cross-validation revealed that the prediction accuracies of these differential lipids and volatile compounds for sex recognition via the random forest model were 100%. These findings might not only provide insight into the effects of sexes on the lipid and volatile profiles of giant salamander tails but also provide clues for their gender recognition. Full article
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11 pages, 1319 KiB  
Communication
Employing Bidirectional Two-Sample Mendelian Randomization Analysis to Verify the Potential of Polyunsaturated Fatty Acid Levels in the Prevention of Pancreatic Cancer
by Hao Sha and Weifeng Zhu
Curr. Issues Mol. Biol. 2024, 46(6), 6041-6051; https://doi.org/10.3390/cimb46060360 - 14 Jun 2024
Cited by 1 | Viewed by 1875
Abstract
Polyunsaturated fatty acids (PUFAs), specifically Omega-3 (FAω3) and docosahexaenoic acid (DHA), have been studied for their potential role in modulating pancreatic cancer (PC) risk. Although observational studies suggest a beneficial effect in reducing this risk, their findings are often limited by confounding variables [...] Read more.
Polyunsaturated fatty acids (PUFAs), specifically Omega-3 (FAω3) and docosahexaenoic acid (DHA), have been studied for their potential role in modulating pancreatic cancer (PC) risk. Although observational studies suggest a beneficial effect in reducing this risk, their findings are often limited by confounding variables and issues of reverse causation. This study used a two-way two-sample Mendelian randomization (MR) method to test the hypothesized genetic causal relationship between PUFAs and PC risk. Data from an extensive genome-wide association study (GWAS) were analyzed, focusing on FAω3 and FAω6 levels, their ratios, and DHA as variables and PC incidence as outcomes. This relationship was comprehensively evaluated using related MR methods, such as inverse variance weighting (IVW), MR Egger, and weighted median (WM). This study finds a significant negative correlation between FAω3 and DHA levels and PC risk, while FAω6 levels show no significant correlation. Interestingly, the ratio of FAω6 to FAω3 was positively associated with increased risk of PC. Neither the MR Egger nor the MR-PRESSO tests detected significant pleiotropy, nor did the Cochrane’s Q test show significant heterogeneity. Leave-one-out analyzes further confirmed the robustness of these results. Using MR analysis of two samples, this study provides genetic causal evidence that FAω3 and DHA levels reduce the risk of PC, whereas the ratio of FAω6 to FAω3 increases the risk of PC. These insights highlight the potential utility of supplementing FAω3 and DHA or altering PUFAs in developing PC prevention strategies. Full article
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21 pages, 7190 KiB  
Article
Solitary and Synergistic Effects of Different Hydrophilic and Hydrophobic Phospholipid Moieties on Rat Behaviors
by Shuhei Kikuchi, Yugo Iwasaki, Mina Yoshioka, Kodai Hino, Shin-ya Morita, Ryu Tada, Yasuhiro Uchimura, Yoshinori Kubo, Tomoya Kobayashi, Yusuke Kinoshita, Masahiro Hayashi, Yoshio Furusho, Hitoshi Tamiaki, Hiroaki Ishiyama, Minoru Kuroda and Jun Udagawa
Pharmaceutics 2024, 16(6), 762; https://doi.org/10.3390/pharmaceutics16060762 - 4 Jun 2024
Cited by 2 | Viewed by 1548
Abstract
Glycerophospholipids have hydrophobic and hydrophilic moieties. Previous studies suggest that phospholipids with different moieties have different effects on rodent behavior; however, the relationship between chemical structures and behavioral effects remains unclear. To clarify the functions of phospholipid moieties, we injected male rats with [...] Read more.
Glycerophospholipids have hydrophobic and hydrophilic moieties. Previous studies suggest that phospholipids with different moieties have different effects on rodent behavior; however, the relationship between chemical structures and behavioral effects remains unclear. To clarify the functions of phospholipid moieties, we injected male rats with phospholipids with different moieties and conducted behavioral tests. Exploratory activity was reduced by phosphatidylethanolamine (PE)(18:0/22:6) but not PE(18:0/18:0) or PE(18:0/20:4). Conversely, exploratory activity was increased by plasmanyl PE(16:0/22:6), which harbors an alkyl–ether linkage, but not by phosphatidylcholine (PC)(16:0/22:6) or plasmanyl PC(16:0/22:6). Docosahexaenoic acid (DHA)(22:6) and an alkyl–ether linkage in PE were thus postulated to be involved in exploratory activity. Anxiety-like behavior was reduced by plasmenyl PC(18:0/20:4), which harbors a vinyl–ether linkage, but not by PC(18:0/20:4) or plasmanyl PC(18:0/20:4), suggesting the anxiolytic effects of vinyl–ether linkage. The activation of social interaction was suppressed by PE(18:0/18:0), PE(18:0/22:6), PC(16:0/22:6), plasmanyl PE(16:0/22:6), and plasmanyl PC(16:0/22:6) but not by PE(18:0/20:4), plasmenyl PE(18:0/20:4), or plasmanyl PC(18:0/22:6). DHA may suppress social interaction, whereas arachidonic acid(20:4) or a combination of alkyl–ether linkage and stearic acid(18:0) may restore social deficits. Our findings indicate the characteristic effects of different phospholipid moieties on rat behavior, and may help to elucidate patterns between chemical structures and their effects. Full article
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19 pages, 889 KiB  
Article
New Forms of Neuroactive Phospholipids for DHA Enrichment in Brain
by Romina Gomes, Inês Mendes, Maria Paula Duarte, Narcisa M. Bandarra and Ana Gomes-Bispo
Mar. Drugs 2024, 22(3), 116; https://doi.org/10.3390/md22030116 - 29 Feb 2024
Cited by 3 | Viewed by 4333
Abstract
Low levels of docosahexaenoic acid (DHA) in the brain have been related to neurological disorders, like Alzheimer’s disease (AD). After ingestion, dietary DHA must cross the blood–brain barrier, where it is absorbed as lysophosphatidylcholine (LPC), due to its role as a preferential DHA [...] Read more.
Low levels of docosahexaenoic acid (DHA) in the brain have been related to neurological disorders, like Alzheimer’s disease (AD). After ingestion, dietary DHA must cross the blood–brain barrier, where it is absorbed as lysophosphatidylcholine (LPC), due to its role as a preferential DHA carrier in the brain. This work aimed at the production of LPC-DHA extracts to be used in supplementation/food fortification intended neural enrichment in DHA. As it is rich in DHA, especially its phospholipids (PL), Atlantic mackerel (Scomber scombrus, caught in Spring/2022) was used as a raw material. The polar lipids fraction was separated and hydrolysed with Rhizomucor miehei lipase, to enzymatically convert phosphatidylcholine (PC) into LPC. The fish (muscle and by-products) lipids fraction was used for total lipids (TL) content, lipid classes (LC) and fatty acid (FA) profile evaluation, whilst polar lipids extracts were studied for LC production and FA analysis. Muscle TL ranged between 1.45 and 4.64 g/100 g (WW), while by-products accounted for 7.56-8.96 g/100 g, with the highest contents being found in March. However, PL were more abundant in muscle (22.46–32.20% of TL). For polar lipids extracts, PL represented 50.79% of TL, among which PC corresponded to 57.76% and phosphatidylethanolamine to 42.24%. After hydrolysis, nearly half of this PC was converted into LPC. When compared to the initial PC, DHA relative content (33.6% of total FA) was significantly higher after hydrolysis: 55.6% in PC and 73.6% in LPC. Such extract, obtained from this undervalued species, may represent a promising strategy to increase DHA uptake into brain cells while allowing this species to upgrade. Full article
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16 pages, 2701 KiB  
Article
Carrier–Tumor Cell Membrane Interactions for Optimized Delivery of a Promising Drug, 4(RS)-4-F4t-Neuroprostane
by Ariana Abawi, Céline Thomann, Giovanna Lollo, Thierry Granjon, Emma Petiot, Anna Bérot, Camille Oger, Valérie Bultel-Poncé, Alexandre Guy, Jean-Marie Galano, Thierry Durand, Agnès Girard-Egrot and Ofelia Maniti
Pharmaceutics 2023, 15(12), 2739; https://doi.org/10.3390/pharmaceutics15122739 - 7 Dec 2023
Cited by 3 | Viewed by 1787
Abstract
Nanomedicines engineered to deliver molecules with therapeutic potentials, overcoming drawbacks such as poor solubility, toxicity or a short half-life, are targeted towards their cellular destination either passively or through various elements of cell membranes. The differences in the physicochemical properties of the cell [...] Read more.
Nanomedicines engineered to deliver molecules with therapeutic potentials, overcoming drawbacks such as poor solubility, toxicity or a short half-life, are targeted towards their cellular destination either passively or through various elements of cell membranes. The differences in the physicochemical properties of the cell membrane between tumor and nontumor cells have been reported, but they are not systematically used for drug delivery purposes. Thus, in this study, a new approach based on a match between the liposome compositions, i.e., membrane fluidity, to selectively interact with the targeted cell membrane was used. Lipid-based carriers of two different fluidities were designed and used to deliver 4(RS)-4-F4t-Neuroprostane (F4t-NeuroP), a potential antitumor molecule derived from docosahexaenoic acid (DHA). Based on its hydrophobic character, F4t-NeuroP was added to the lipid mixture prior to liposome formation, a protocol that yielded over 80% encapsulation efficiency in both rigid and fluid liposomes. The presence of the active molecule did not modify the liposome size but increased the liposome negative charge and the liposome membrane fluidity, which suggested that the active molecule was accommodated in the lipid membrane. F4t-NeuroP integration in liposomes with a fluid character allowed for the selective targeting of the metastatic prostate cell line PC-3 vs. fibroblast controls. A significant decrease in viability (40%) was observed for the PC-3 cancer line in the presence of F4t-NeuroP fluid liposomes, whereas rigid F4t-NeuroP liposomes did not alter the PC-3 cell viability. These findings demonstrate that liposomes encapsulating F4t-NeuroP or other related molecules may be an interesting model of drug carriers based on membrane fluidity. Full article
(This article belongs to the Special Issue Nano-Drug Carriers Based on Membrane Fluidity)
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14 pages, 1351 KiB  
Article
Dynamics of Docosahexaenoic Acid Utilization by Mouse Peritoneal Macrophages
by Patricia Monge, Alma M. Astudillo, Laura Pereira, María A. Balboa and Jesús Balsinde
Biomolecules 2023, 13(11), 1635; https://doi.org/10.3390/biom13111635 - 10 Nov 2023
Cited by 1 | Viewed by 1851
Abstract
In this work, the incorporation of docosahexaenoic acid (DHA) in mouse resident peritoneal macrophages and its redistribution within the various phospholipid classes were investigated. Choline glycerophospholipids (PC) behaved as the major initial acceptors of DHA. Prolonged incubation with the fatty acid resulted in [...] Read more.
In this work, the incorporation of docosahexaenoic acid (DHA) in mouse resident peritoneal macrophages and its redistribution within the various phospholipid classes were investigated. Choline glycerophospholipids (PC) behaved as the major initial acceptors of DHA. Prolonged incubation with the fatty acid resulted in the transfer of DHA from PC to ethanolamine glycerophospholipids (PE), reflecting phospholipid remodeling. This process resulted in the cells containing similar amounts of DHA in PC and PE in the resting state. Mass spectrometry-based lipidomic analyses of phospholipid molecular species indicated a marked abundance of DHA in ether phospholipids. Stimulation of the macrophages with yeast-derived zymosan resulted in significant decreases in the levels of all DHA-containing PC and PI species; however, no PE or PS molecular species were found to decrease. In contrast, the levels of an unusual DHA-containing species, namely PI(20:4/22:6), which was barely present in resting cells, were found to markedly increase under zymosan stimulation. The levels of this phospholipid also significantly increased when the calcium-ionophore A23187 or platelet-activating factor were used instead of zymosan to stimulate the macrophages. The study of the route involved in the synthesis of PI(20:4/22:6) suggested that this species is produced through deacylation/reacylation reactions. These results define the increases in PI(20:4/22:6) as a novel lipid metabolic marker of mouse macrophage activation, and provide novel information to understand the regulation of phospholipid fatty acid turnover in activated macrophages. Full article
(This article belongs to the Collection Feature Papers in Lipids)
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13 pages, 4031 KiB  
Article
Dietary Phospholipids Alleviate Diet-Induced Obesity in Mice: Which Fatty Acids and Which Polar Head
by Lingyu Zhang, Jiaqin Mu, Jing Meng, Wenjin Su and Jian Li
Mar. Drugs 2023, 21(11), 555; https://doi.org/10.3390/md21110555 - 25 Oct 2023
Cited by 3 | Viewed by 2799
Abstract
The weight loss effects of dietary phospholipids have been extensively studied. However, little attention has been paid to the influence of phospholipids (PLs) with different fatty acids and polar headgroups on the development of obesity. High-fat-diet-fed mice were administrated with different kinds of [...] Read more.
The weight loss effects of dietary phospholipids have been extensively studied. However, little attention has been paid to the influence of phospholipids (PLs) with different fatty acids and polar headgroups on the development of obesity. High-fat-diet-fed mice were administrated with different kinds of PLs (2%, w/w) with specific fatty acids and headgroups, including EPA-enriched phosphatidylcholine/phosphatidylethanolamine/phosphatidylserine (EPA-PC/PE/PS), DHA-PC/PE/PS, Egg-PC/PE/PS, and Soy-PC/PE/PS for eight weeks. Body weight, white adipose tissue weight, and the levels of serum lipid and inflammatory markers were measured. The expression of genes related to lipid metabolism in the liver were determined. The results showed that PLs decreased body weight, fat storage, and circulating lipid levels, and EPA-PLs had the best efficiency. Serum TNF-α, MCP-1 levels were significantly reduced via treatment with DHA-PLs and PS groups. Mechanistic investigation revealed that PLs, especially EPA-PLs and PSs, reduced fat accumulation through enhancing the expression of genes involved in fatty acid β-oxidation (Cpt1a, Cpt2, Cd36, and Acaa1a) and downregulating lipogenesis gene (Srebp1c, Scd1, Fas, and Acc) expression. These data suggest that EPA-PS exhibits the best effects among other PLs in terms of ameliorating obesity, which might be attributed to the fatty acid composition of phospholipids, as well as their headgroup. Full article
(This article belongs to the Special Issue Marine Fish Oils as Functional Foods)
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15 pages, 3728 KiB  
Article
Lysophosphatidylcholine-DHA Specifically Induces Cytotoxic Effects of the MDA-MB-231 Human Breast Cancer Cell Line In Vitro—Comparative Effects with Other Lipids Containing DHA
by Dalal Mohamad Ali, Kevin Hogeveen, Rose-Marie Orhant, Tiphaine Le Gal de Kerangal, Françoise Ergan, Lionel Ulmann and Gaëlle Pencreac’h
Nutrients 2023, 15(9), 2137; https://doi.org/10.3390/nu15092137 - 29 Apr 2023
Cited by 5 | Viewed by 4135
Abstract
Docosahexaenoic acid (DHA, C22:6 ω-3) is a dietary polyunsaturated fatty acid that has an important role in human health. Epidemiological studies linked a high intake of DHA to a reduced risk of certain cancers. Recently, attention focused on how the lipid carrier in [...] Read more.
Docosahexaenoic acid (DHA, C22:6 ω-3) is a dietary polyunsaturated fatty acid that has an important role in human health. Epidemiological studies linked a high intake of DHA to a reduced risk of certain cancers. Recently, attention focused on how the lipid carrier in which DHA is delivered, i.e., esterified on acylglycerols, phospholipids, or free, affects its biological effects. However, studies comparing the effects of these different forms for DHA supply to cancer cells in vitro are limited. In this study, the effect of free DHA and five lipids carrying one to three DHA chains (LPC-DHA, PC-DHA, MAG-DHA, DAG-DHA and TAG-DHA) on the viability of the MDA-MB-231 breast cancer cell line was compared. Our results revealed a strong structure–function relationship of DHA-carrying lipids on the viability of MDA-MB-231 cells. Glycerophosphocholine-based lipids are the most effective DHA carriers in reducing the viability of MDA-MB-231 cells, with LPC-DHA being more effective (IC50 = 23.7 µM) than PC-DHA (IC50 = 67 µM). The other tested lipids are less toxic (MAG-DHA, free DHA) or even not toxic (DAG-DHA, TAG-DHA) under our conditions. Investigating the mechanism of cell death induced by LPC-DHA revealed increased oxidative stress and membrane cell damage. Full article
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