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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 -
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 -
Experimental & Molecular Medicine Sep 2020In recent decades, the role of the peroxisome in physiology and disease conditions has become increasingly important. Together with the mitochondria and other cellular... (Review)
Review
In recent decades, the role of the peroxisome in physiology and disease conditions has become increasingly important. Together with the mitochondria and other cellular organelles, peroxisomes support key metabolic platforms for the oxidation of various fatty acids and regulate redox conditions. In addition, peroxisomes contribute to the biosynthesis of essential lipid molecules, such as bile acid, cholesterol, docosahexaenoic acid, and plasmalogen. Therefore, the quality control mechanisms that regulate peroxisome biogenesis and degradation are important for cellular homeostasis. Current evidence indicates that peroxisomal function is often reduced or dysregulated in various human disease conditions, such as neurodegenerative diseases. Here, we review the recent progress that has been made toward understanding the quality control systems that regulate peroxisomes and their pathological implications.
Topics: Animals; Biomarkers; Disease Susceptibility; Endoplasmic Reticulum; Homeostasis; Humans; Lipid Metabolism; Metabolic Networks and Pathways; Neurodegenerative Diseases; Oxidation-Reduction; Peroxisomes; Protein Processing, Post-Translational
PubMed: 32917959
DOI: 10.1038/s12276-020-00503-9 -
Foods (Basel, Switzerland) Aug 2023Plasmalogen, a functional glycerophospholipid, is known for its beneficial nutritional effects, such as anti-oxidation and anti-inflammation. As the porcine brain is a...
Plasmalogen, a functional glycerophospholipid, is known for its beneficial nutritional effects, such as anti-oxidation and anti-inflammation. As the porcine brain is a plasmalogen-rich resource, this study aimed to explore its potential for plasmalogen-based health food product development, with special attention on whether and how the industrial production processes influence the plasmalogen content and composition. In the present work, plasmalogens from different porcine brain products were investigated using liquid chromatography-tandem mass spectrometry. The results indicated that all the porcine brain products showed abundant total plasmalogens, of which more than 95% were ethanolamine plasmalogen species. Acetone precipitation, ethanol extraction, and drying did not significantly affect the plasmalogen content, whereas repeated freeze-thaw cycles in the production process led to noticeable loss. The chemometric investigation suggested that raw products and glycerophospholipid products exhibited different profiles; furthermore, the concentration step seemed to impact the plasmalogen composition. The nutritional assessment revealed that porcine brain products showed favorable values of multiple indexes, including PUFA/SFA ratio, n-6/n-3 ratio, thrombogenicity index, and unsaturation index, suggesting a health-beneficial value. The current study not only shows the feasibility of producing porcine brain-derived plasmalogens, but also provides possible strategies for developing and quality-controlling dietary plasmalogen supplements and healthcare products.
PubMed: 37627989
DOI: 10.3390/foods12162990 -
Scientific Reports Feb 2023The underlying mechanisms linking physical activity to better health are not fully understood. Here we examined the associations between physical activity and small...
The underlying mechanisms linking physical activity to better health are not fully understood. Here we examined the associations between physical activity and small circulatory molecules, the metabolome, to highlight relevant biological pathways. We examined plasma metabolites associated with self-reported physical activity among 2217 participants from the Airwave Health Monitoring Study. Metabolic profiling was conducted using the mass spectrometry-based Metabolon platform (LC/GC-MS), measuring 828 known metabolites. We replicated our findings in an independent subset of the study (n = 2971) using untargeted LC-MS. Mendelian randomisation was carried out to investigate potential causal associations between physical activity, body mass index, and metabolites. Higher vigorous physical activity was associated (P < 0.05/828 = 6.03 × 10) with circulatory levels of 28 metabolites adjusted for age, sex and body mass index. The association was inverse for glutamate and diacylglycerol lipids, and direct for 3-4-hydroxyphenyllactate, phenyl lactate (PLA), alpha-hydroxy isovalerate, tiglylcarnitine, alpha-hydroxyisocaproate, 2-hydroxy-3-methylvalerate, isobutyrylcarnitine, imidazole lactate, methionine sulfone, indole lactate, plasmalogen lipids, pristanate and fumarate. In the replication panel, we found 23 untargeted LC-MS features annotated to the identified metabolites, for which we found nominal associations with the same direction of effect for three features annotated to 1-(1-enyl-palmitoyl)-2-oleoyl-GPC (P-16:0/18:1), 1-(1-enyl-palmitoyl)-2-linoleoyl-GPC (P-16:0/18:2), 1-stearoyl-2-dihomo-linolenoyl-GPC (18:0/20:3n3 or 6). Using Mendelian randomisation, we showed a potential causal relationship between body mass index and three identified metabolites. Circulatory metabolites are associated with physical activity and may play a role in mediating its health effects.
Topics: Humans; Metabolome; Metabolomics; Exercise; Fatty Acids; Lactates
PubMed: 36759570
DOI: 10.1038/s41598-022-26377-7 -
Advanced Science (Weinheim,... Jun 2023Meat is among the most consumed foods worldwide and has a unique flavor and high nutrient density in the human diet. However, the genetic and biochemical bases of meat...
Meat is among the most consumed foods worldwide and has a unique flavor and high nutrient density in the human diet. However, the genetic and biochemical bases of meat nutrition and flavor are poorly understood. Here, 3431 metabolites and 702 volatiles in 423 skeletal muscle samples are profiled from a gradient consanguinity segregating population generated by Pekin duck × Liancheng duck crosses using metabolomic approaches. The authors identified 2862 metabolome-based genome-wide association studies (mGWAS) signals and 48 candidate genes potentially modulating metabolite and volatile levels, 79.2% of which are regulated by cis-regulatory elements. The level of plasmalogen is significantly associated with TMEM189 encoding plasmanylethanolamine desaturase 1. The levels of 2-pyrrolidone and glycerophospholipids are regulated by the gene expression of AOX1 and ACBD5, which further affects the levels of volatiles, 2-pyrrolidone and decanal, respectively. Genetic variations in GADL1 and CARNMT2 determine the levels of 49 metabolites including L-carnosine and anserine. This study provides novel insights into the genetic and biochemical basis of skeletal muscle metabolism and constitutes a valuable resource for the precise improvement of meat nutrition and flavor.
Topics: Animals; Humans; Genome-Wide Association Study; Ducks; Meat; Metabolome; Muscle, Skeletal; Carboxy-Lyases
PubMed: 37013465
DOI: 10.1002/advs.202300148 -
Biotechnology Advances 2021The energy crisis, depletion of oil reserves, and global climate changes are pressing problems of developed societies. One possibility to counteract that is microbial... (Review)
Review
The energy crisis, depletion of oil reserves, and global climate changes are pressing problems of developed societies. One possibility to counteract that is microbial production of butanol, a promising new fuel and alternative to many petrochemical reagents. However, the high butanol toxicity to all known microbial species is the main obstacle to its industrial implementation. The present state of the art review aims to expound the recent advances in modern omics approaches to resolving this insurmountable to date problem of low butanol tolerance. Genomics, transcriptomics, and proteomics show that butanol tolerance is a complex phenomenon affecting multiple genes and their expression. Efflux pumps, stress and multidrug response, membrane transport, and redox-related genes are indicated as being most important during butanol challenge, in addition to fine-tuning of global regulators of transcription (Spo0A, GntR), which may further improve tolerance. Lipidomics shows that the alterations in membrane composition (saturated lipids and plasmalogen increase) are very much species-specific and butanol-related. Glycomics discloses the pleiotropic effect of CcpA, the role of alternative sugar transport, and the production of exopolysaccharides as alternative routes to overcoming butanol stress. Unfortunately, the strain that simultaneously syntheses and tolerates butanol in concentrations that allow its commercialization has not yet been discovered or produced. Omics insight will allow the purposeful increase of butanol tolerance in natural and engineered producers and the effective heterologous expression of synthetic butanol pathways in strains hereditary butanol-resistant up to 3.2 - 4.9% (w/v). Future breakthrough can be achieved by a detailed study of the membrane proteome, of which 21% are proteins with unknown functions.
Topics: 1-Butanol; Butanols; Proteome; Proteomics
PubMed: 33220435
DOI: 10.1016/j.biotechadv.2020.107658 -
Foods (Basel, Switzerland) Jan 2021Plasmalogens are an animal-derived functional phospholipid increasingly known as a safe and effective nutritional ingredient, however, the quantitation and comparison of...
Plasmalogens are an animal-derived functional phospholipid increasingly known as a safe and effective nutritional ingredient, however, the quantitation and comparison of plasmalogen species in foods is limited. In the present work, determination methods for dietary plasmalogens using liquid chromatography-tandem mass spectroscopy under positive and negative ionization modes were compared. The negative-mode method, which showed better selectivity, sensitivity, and accuracy, was then applied in 14 kinds of livestock, poultry, and seafood samples. Livestock and poultry showed abundant total plasmalogen (530.83-944.94 nmol/g), higher than fish (46.08-399.75 nmol/g) and mollusk (10.00-384.76 nmol/g). While fish and mollusk samples expressed healthier fatty acyl composition, with higher eicosapentaenoyl and more beneficial n-6/n-3 ratio than the land animal meats, especially for squid and octopus, with eicosapentaenoyl of 98.4% and 94.5%, respectively. The correlations among plasmalogen species varied in different foodstuffs with distinguishing patterns, suggesting the customizable strategies for achieving targeted plasmalogen species. These findings not only provided fundamental comparison of plasmalogen among daily foodstuffs, but also contributed to extend the dietary plasmalogen sources for health food development.
PubMed: 33435634
DOI: 10.3390/foods10010124 -
Medicine and Science in Sports and... Oct 2023The aim of this study was to understand the serum metabolomic signatures of moderate-to-vigorous physical activity (MVPA) and sedentary behavior, and further associate...
PURPOSE
The aim of this study was to understand the serum metabolomic signatures of moderate-to-vigorous physical activity (MVPA) and sedentary behavior, and further associate their metabolomic signatures with incident cardiometabolic diseases.
METHODS
This analysis included 2711 US Hispanics/Latinos from the Hispanic Community Health Study/Study of Latinos (HCHS/SOL) aged 18-74 yr (2008-2011). An untargeted, liquid chromatography-mass spectrometry was used to profile the serum metabolome. The associations of metabolites with accelerometer-measured MVPA and sedentary time were examined using survey linear regressions adjusting for covariates. The weighted correlation network analysis identified modules of correlated metabolites in relation to sedentary time, and the modules were associated with incident diabetes, dyslipidemia, and hypertension over the 6-yr follow-up.
RESULTS
Of 624 metabolites, 5 and 102 were associated with MVPA and sedentary behavior at false discovery rate (FDR) <0.05, respectively, after adjusting for socioeconomic and lifestyle factors. The weighted correlation network analysis identified 8 modules from 102 metabolites associated with sedentary time. Four modules (branched-chain amino acids, erythritol, polyunsaturated fatty acid, creatine) were positively, and the other four (acyl choline, plasmalogen glycerol phosphatidyl choline, plasmalogen glycerol phosphatidyl ethanolamine, urea cycle) were negatively correlated with sedentary time. Among these modules, a higher branched-chain amino acid score and a lower plasmalogen glycerol phosphatidyl choline score were associated with increased risks of diabetes and dyslipidemia. A higher erythritol score was associated with an increased risk of diabetes, and a lower acyl choline score was linked to an increased risk of hypertension.
CONCLUSIONS
In this study of US Hispanics/Latinos, we identified multiple serum metabolomic signatures of sedentary behavior and their associations with risk of incident diabetes, hypertension, and dyslipidemia. These findings suggest a potential role of circulating metabolites in the links between sedentary behavior and cardiometabolic diseases.
Topics: Humans; Cardiovascular Diseases; Diabetes Mellitus; Glycerol; Hispanic or Latino; Hypertension; Metabolome; Plasmalogens; Risk Factors; Sedentary Behavior; Adolescent; Young Adult; Adult; Middle Aged; Aged
PubMed: 37170952
DOI: 10.1249/MSS.0000000000003205