-
Brain Research Bulletin Jan 2023Neuroinflammation (NF) is defined as the activation of brain glial cells that are found in neurodegenerative diseases including Alzheimer's disease (AD). It has been... (Review)
Review
Neuroinflammation (NF) is defined as the activation of brain glial cells that are found in neurodegenerative diseases including Alzheimer's disease (AD). It has been known that an increase in NF could reduce the memory process in the brain but the key factors, associated with NF, behind the dysregulation of memory remained elusive. We previously reported that the NF and aging processes reduced the special phospholipids, plasmalogens (Pls), in the murine brain by a mechanism dependent on the activation of transcription factors, NF-kB and c-MYC. A similar mechanism has also been found in postmortem human brain tissues with AD pathologies and in the AD model mice. Recent evidence showed that these phospholipids enhanced memory and reduced neuro-inflammation in the murine brain. Pls can stimulate the cellular signaling molecules, ERK and Akt, by activating the membrane-bound G protein-coupled receptors (GPCRs). Therefore, recent findings suggest that plasmalogens could be one of the key phospholipids in the brain to enhance memory and inhibit NF.
Topics: Animals; Mice; Humans; Plasmalogens; Signal Transduction; Alzheimer Disease; Cognition; Brain; NF-kappa B
PubMed: 36347405
DOI: 10.1016/j.brainresbull.2022.11.005 -
European Journal of Preventive... Oct 2023To evaluate the associations of dietary indices and quantitative cardiorespiratory fitness (CRF) measures in a large, community-based sample harnessing metabolomic...
AIMS
To evaluate the associations of dietary indices and quantitative cardiorespiratory fitness (CRF) measures in a large, community-based sample harnessing metabolomic profiling to interrogate shared biology.
METHODS AND RESULTS
Framingham Heart Study (FHS) participants underwent maximum effort cardiopulmonary exercise tests for CRF quantification (via peak VO2) and completed semi-quantitative food frequency questionnaires. Dietary quality was assessed by the Alternative Healthy Eating Index (AHEI) and Mediterranean-style Diet Score (MDS), and fasting blood concentrations of 201 metabolites were quantified. In 2380 FHS participants (54 ± 9 years, 54% female, body mass index 28 ± 5 kg/m2), 1 SD higher AHEI and MDS were associated with 5.2% (1.2 mL/kg/min, 95% CI 4.3-6.0%, P < 0.0001) and 4.5% (1.0 mL/kg/min, 95% CI 3.6-5.3%, P < 0.0001) greater peak VO2 in linear models adjusted for age, sex, total daily energy intake, cardiovascular risk factors, and physical activity. In participants with metabolite profiling (N = 1154), 24 metabolites were concordantly associated with both dietary indices and peak VO2 in multivariable-adjusted linear models (FDR < 5%). Metabolites that were associated with lower CRF and poorer dietary quality included C6 and C7 carnitines, C16:0 ceramide, and dimethylguanidino valeric acid, and metabolites that were positively associated with higher CRF and favourable dietary quality included C38:7 phosphatidylcholine plasmalogen and C38:7 and C40:7 phosphatidylethanolamine plasmalogens.
CONCLUSION
Higher diet quality is associated with greater CRF cross-sectionally in a middle-aged community-dwelling sample, and metabolites highlight potential shared favourable effects on cardiometabolic health.
Topics: Middle Aged; Humans; Female; Male; Cardiorespiratory Fitness; Health Status; Exercise; Diet, Healthy; Diet, Mediterranean
PubMed: 37164358
DOI: 10.1093/eurjpc/zwad113 -
Protein & Cell Feb 2018Ether lipids, such as plasmalogens, are peroxisome-derived glycerophospholipids in which the hydrocarbon chain at the sn-1 position of the glycerol backbone is attached... (Review)
Review
Ether lipids, such as plasmalogens, are peroxisome-derived glycerophospholipids in which the hydrocarbon chain at the sn-1 position of the glycerol backbone is attached by an ether bond, as opposed to an ester bond in the more common diacyl phospholipids. This seemingly simple biochemical change has profound structural and functional implications. Notably, the tendency of ether lipids to form non-lamellar inverted hexagonal structures in model membranes suggests that they have a role in facilitating membrane fusion processes. Ether lipids are also important for the organization and stability of lipid raft microdomains, cholesterol-rich membrane regions involved in cellular signaling. In addition to their structural roles, a subset of ether lipids are thought to function as endogenous antioxidants, and emerging studies suggest that they are involved in cell differentiation and signaling pathways. Here, we review the biology of ether lipids and their potential significance in human disorders, including neurological diseases, cancer, and metabolic disorders.
Topics: Animals; Disease; Ether; Humans; Lipid Metabolism; Lipids
PubMed: 28523433
DOI: 10.1007/s13238-017-0423-5 -
Lipids in Health and Disease Mar 2018The plasmalogens are a class of glycerophospholipids which contain a vinyl-ether and an ester bond at the sn-1 and sn-2 positions, respectively, in the glycerol... (Review)
Review
The plasmalogens are a class of glycerophospholipids which contain a vinyl-ether and an ester bond at the sn-1 and sn-2 positions, respectively, in the glycerol backbone. They constitute 10 mol% of the total mass of phospholipids in humans, mainly as membrane structure components. Plasmalogens are important for the organization and stability of lipid raft microdomains and cholesterol-rich membrane regions involved in cellular signaling. In addition to their structural roles, a subset of ether lipids are thought to function as endogenous antioxidants and emerging studies suggest that they are involved in cell differentiation and signaling pathways. Although the clinical significance of plasmalogens is linked to peroxisomal disorders, the pathophysiological roles and their possible metabolic pathways are not fully understood since they present unique structural attributes for the different tissue types. Studies suggest that changes in plasmalogen metabolism may contribute to the development of various types of cancer. Here, we review the molecular characteristics of plasmalogens in order to significantly increase our understanding of the plasmalogen molecule and its involvement in gastrointestinal cancers as well as other types of cancers.
Topics: Antineoplastic Agents; Biomarkers, Tumor; Gastrointestinal Neoplasms; Humans; Lipid Metabolism; Phospholipid Ethers; Plasmalogens
PubMed: 29514688
DOI: 10.1186/s12944-018-0685-9 -
Marine Drugs Dec 2022Τhis mini-review summarizes the hematopoietic and immunostimulating properties of alkyl glycerol ethers (AGs) reported earlier in the literature available to us. The...
Τhis mini-review summarizes the hematopoietic and immunostimulating properties of alkyl glycerol ethers (AGs) reported earlier in the literature available to us. The role of AGs in the nervous system and aging of the body are also briefly described. We made an attempt to consider the data in terms of adaptation. The hematopoietic, immunostimulating and antioxidant properties of AGs in a variety of experimental situations, including stress, as well as the protective action of AGs against some adaptation diseases, allow us to consider them as substances that prevent some negative effects of stress and promote adaptation. The new approach to AGs as adaptogens seems promising and opens good opportunities for their new application.
Topics: Glyceryl Ethers; Adaptation, Physiological; Antioxidants; Ethers; Glycerol
PubMed: 36662177
DOI: 10.3390/md21010004 -
Frontiers in Cell and Developmental... 2022Plasmalogens are plasma-borne antioxidant phospholipid species that provide protection as cellular lipid components during cellular oxidative stress. In this study we...
Plasmalogens are plasma-borne antioxidant phospholipid species that provide protection as cellular lipid components during cellular oxidative stress. In this study we investigated plasma plasmalogen levels in human sepsis as well as in rodent models of infection. In humans, levels of multiple plasmenylethanolamine molecular species were decreased in septic patient plasma compared to control subject plasma as well as an age-aligned control subject cohort. Additionally, lysoplasmenylcholine levels were significantly decreased in septic patients compared to the control cohorts. In contrast, plasma diacyl phosphatidylethanolamine and phosphatidylcholine levels were elevated in septic patients. Lipid changes were also determined in rats subjected to cecal slurry sepsis. Plasma plasmenylcholine, plasmenylethanolamine, and lysoplasmenylcholine levels were decreased while diacyl phosphatidylethanolamine levels were increased in septic rats compared to control treated rats. Kidney levels of lysoplasmenylcholine as well as plasmenylethanolamine molecular species were decreased in septic rats. Interestingly, liver plasmenylcholine and plasmenylethanolamine levels were increased in septic rats. Since COVID-19 is associated with sepsis-like acute respiratory distress syndrome and oxidative stress, plasmalogen levels were also determined in a mouse model of COVID-19 (intranasal inoculation of K18 mice with SARS-CoV-2). 3 days following infection, lung infection was confirmed as well as cytokine expression in the lung. Multiple molecular species of lung plasmenylcholine and plasmenylethanolamine were decreased in infected mice. In contrast, the predominant lung phospholipid, dipalmitoyl phosphatidylcholine, was not decreased following SARS-CoV-2 infection. Additionally total plasmenylcholine levels were decreased in the plasma of SARS-CoV-2 infected mice. Collectively, these data demonstrate the loss of plasmalogens during both sepsis and SARS-CoV-2 infection. This study also indicates plasma plasmalogens should be considered in future studies as biomarkers of infection and as prognostic indicators for sepsis and COVID-19 outcomes.
PubMed: 35784479
DOI: 10.3389/fcell.2022.912880 -
Bioscience, Biotechnology, and... May 2021A concise synthesis of a plasmenylethanolamine (PlsEtn-[16:0/18:1 n-9]), known as antioxidative phospholipids commonly found in cell membranes, has been achieved from an...
A concise synthesis of a plasmenylethanolamine (PlsEtn-[16:0/18:1 n-9]), known as antioxidative phospholipids commonly found in cell membranes, has been achieved from an optically active known diol through 8 steps. The key transformations for the synthesis of PlsEtn-[16:0/18:1 n-9] are (1) regio- and Z-selective vinyl ether formation via the alkylation of a lithioalkoxy allyl intermediate with an alkyl iodide, and (2) a one-pot phosphite esterification-oxidation sequence to construct the ethanolamine phosphonate moiety in the presence of the vinyl ether functionality. The piperidine salt of synthetic PlsEtn-[16:0/18:1 n-9] was desalinated through reversed-phase high-performance liquid chromatography purification.
Topics: Chemistry Techniques, Synthetic; Esterification; Oxidation-Reduction; Plasmalogens; Stereoisomerism
PubMed: 33705523
DOI: 10.1093/bbb/zbab037 -
Progress in Lipid Research Apr 2019Plasmalogens are a class of membrane glycerophospholipids with unique properties. They contain a vinyl-ether linked alkyl chain at the sn-1 position of the glycerol... (Review)
Review
Plasmalogens are a class of membrane glycerophospholipids with unique properties. They contain a vinyl-ether linked alkyl chain at the sn-1 position of the glycerol backbone and, typically, a polyunsaturated fatty acyl chain at the sn-2 position. Plasmalogens are critical for human health and have established roles in neuronal development, the immune response and as endogenous antioxidants. However, the mechanistic bases of these and other biological functions of plasmalogens are not well defined. Lipidomic studies have characterised reduced levels of plasmalogens in a number of disease states, including neurodegenerative and cardiometabolic disease, highlighting the potential of plasmalogen modulation as a therapeutic strategy. A number of approaches have been proposed to upregulate plasmalogen levels in different clinical settings; these include dietary intervention with inositol or the naturally occurring metabolic precursors known as alkylglycerols. Plasmalogen modulation has been utilised in both preclinical and clinical studies to prevent onset and/or attenuate progression of neurodegenerative diseases, atherosclerosis, insulin resistance and hepatosteatosis. These studies are providing new insight into the mechanistic role of plasmalogens in disease and their therapeutic potential. In this review, we will examine the strategies for plasmalogen modulation and recent progress toward therapeutic applications with a focus on neurodegenerative and cardiometabolic disease.
Topics: Animals; Cardiovascular Diseases; Fish Oils; Glycerol; Humans; Molecular Structure; Neurodegenerative Diseases; Plasmalogens
PubMed: 30974122
DOI: 10.1016/j.plipres.2019.04.003 -
Biology of Sex Differences Sep 2023We have previously reported that maternal obesity reduces placental transport capacity for lysophosphatidylcholine-docosahexaenoic acid (LPC-DHA), a preferred form for...
BACKGROUND
We have previously reported that maternal obesity reduces placental transport capacity for lysophosphatidylcholine-docosahexaenoic acid (LPC-DHA), a preferred form for transfer of DHA (omega 3) to the fetal brain, but only in male fetuses. Phosphatidylethanolamine (PE) and phosphatidylcholine (PC), have either sn-1 ester, ether or vinyl ether (plasmalogen) linkages to primarily unsaturated and monounsaturated fatty acids and DHA or arachidonic acid (ARA, omega 6) in the sn-2 position. Whether ether and plasmalogen PC and PE metabolism in placenta impacts transfer to the fetus is unexplored. We hypothesized that ether and plasmalogen PC and PE containing DHA and ARA are reduced in maternal-fetal unit in pregnancies complicated by obesity and these differences are dependent on fetal sex.
METHODS
In maternal, umbilical cord plasma and placentas from obese women (11 female/5 male infants) and normal weight women (9 female/7 male infants), all PC and PE species containing DHA and ARA were analyzed by LC-MS/MS. Placental protein expression of enzymes involved in phospholipid synthesis, were determined by immunoblotting. All variables were compared between control vs obese groups and separated by fetal sex, in each sample using the Benjamini-Hochberg false discovery rate adjustment to account for multiple testing.
RESULTS
Levels of ester PC containing DHA and ARA were profoundly reduced by 60-92% in male placentas of obese mothers, while levels of ether and plasmalogen PE containing DHA and ARA were decreased by 51-84% in female placentas. PLA2G4C abundance was lower in male placentas and LPCAT4 abundance was lower solely in females in obesity. In umbilical cord, levels of ester, ether and plasmalogen PC and PE with DHA were reduced by 43-61% in male, but not female, fetuses of obese mothers.
CONCLUSIONS
We found a fetal sex effect in placental PE and PC ester, ether and plasmalogen PE and PC containing DHA in response to maternal obesity which appears to reflect an ability of female placentas to adapt to maintain optimal fetal DHA transfer in maternal obesity.
Topics: Infant; Female; Humans; Male; Pregnancy; Placenta; Phosphatidylcholines; Phosphatidylethanolamines; Plasmalogens; Ether; Obesity, Maternal; Sex Characteristics; Chromatography, Liquid; Tandem Mass Spectrometry; Obesity; Ethyl Ethers; Ethers
PubMed: 37770949
DOI: 10.1186/s13293-023-00548-1 -
Proceedings of the Japan Academy.... 2016Peroxisome is a single-membrane-bounded ubiquitous organelle containing a hundred different enzymes that catalyze various metabolic pathways such as β-oxidation of very... (Review)
Review
Peroxisome is a single-membrane-bounded ubiquitous organelle containing a hundred different enzymes that catalyze various metabolic pathways such as β-oxidation of very long-chain fatty acids and synthesis of plasmalogens. To investigate peroxisome biogenesis and human peroxisome biogenesis disorders (PBDs) including Zellweger syndrome, more than a dozen different complementation groups of Chinese hamster ovary (CHO) cell mutants impaired in peroxisome biogenesis are isolated as a model experimental system. By taking advantage of rapid functional complementation assay of the CHO cell mutants, successful cloning of PEX genes encoding peroxins required for peroxisome assembly invaluably contributed to the accomplishment of cloning of pathogenic genes responsible for PBDs. Peroxins are divided into three groups: 1) peroxins including Pex3p, Pex16p and Pex19p, are responsible for peroxisome membrane biogenesis via Pex19p- and Pex3p-dependent class I and Pex19p- and Pex16p-dependent class II pathways; 2) peroxins that function in matrix protein import; 3) those such as Pex11pβ are involved in peroxisome division where DLP1, Mff, and Fis1 coordinately function.
Topics: Animals; CHO Cells; Cricetinae; Cricetulus; Humans; Peroxisomal Disorders; Peroxisomes
PubMed: 27941306
DOI: 10.2183/pjab.92.463