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Biochemistry and Biophysics Reports Jul 2024Cancer is the major cause of premature death in humans worldwide, demanding more efficient therapeutics. Aberrant cell proliferation resulting from the loss of cell...
Cancer is the major cause of premature death in humans worldwide, demanding more efficient therapeutics. Aberrant cell proliferation resulting from the loss of cell cycle regulation is the major hallmark of cancer, so targeting cell cycle is a promising strategy to combat cancer. However, the molecular mechanism underlying the dysregulation of cell cycle of cancer cells remains poorly understood. TMEM189, a newly identified protein, plays roles in the biosynthesis of ethanolamine plasmalogen and the regulation of autophagy. Here, we demonstrated that the expression level of TMEM189 was negatively correlated with the survival rate of the cancer patients. TMEM189 deficiency significantly suppresses the cancer cell proliferation and migration, and causes cell cycle G2/M arrest both and . Furthermore, TMEM189 depletion suppressed the growth of breast tumors . Taken together, our work indicated that TMEM189 promotes cancer progression by regulating cell cycle G2/M transition, suggesting that it is a promising target in cancer therapy.
PubMed: 38873225
DOI: 10.1016/j.bbrep.2024.101744 -
EBioMedicine Jun 2024Decreased levels of circulating ethanolamine plasmalogens [PE(P)], and a concurrent increase in phosphatidylethanolamine (PE) are consistently reported in various...
Development and validation of a plasmalogen score as an independent modifiable marker of metabolic health: population based observational studies and a placebo-controlled cross-over study.
BACKGROUND
Decreased levels of circulating ethanolamine plasmalogens [PE(P)], and a concurrent increase in phosphatidylethanolamine (PE) are consistently reported in various cardiometabolic conditions. Here we devised, a plasmalogen score (Pls Score) that mirrors a metabolic signal that encompasses the levels of PE(P) and PE and captures the natural variation in circulating plasmalogens and perturbations in their metabolism associated with disease, diet, and lifestyle.
METHODS
We utilised, plasma lipidomes from the Australian Obesity, Diabetes and Lifestyle study (AusDiab; n = 10,339, 55% women) a nationwide cohort, to devise the Pls Score and validated this in the Busselton Health Study (BHS; n = 4,492, 56% women, serum lipidome) and in a placebo-controlled crossover trial involving Shark Liver Oil (SLO) supplementation (n = 10, 100% men). We examined the association of the Pls Score with cardiometabolic risk factors, type 2 diabetes mellitus (T2DM), cardiovascular disease and all-cause mortality (over 17 years).
FINDINGS
In a model, adjusted for age, sex and BMI, individuals in the top quintile of the Pls Score (Q5) relative to Q1 had an OR of 0.31 (95% CI 0.21-0.43), 0.39 (95% CI 0.25-0.61) and 0.42 (95% CI 0.30-0.57) for prevalent T2DM, incident T2DM and prevalent cardiovascular disease respectively, and a 34% lower mortality risk (HR = 0.66; 95% CI 0.56-0.78). Significant associations between diet and lifestyle habits and Pls Score exist and these were validated through dietary supplementation of SLO that resulted in a marked change in the Pls Score.
INTERPRETATION
The Pls Score as a measure that captures the natural variation in circulating plasmalogens, was not only inversely related to cardiometabolic risk and all-cause mortality but also associate with diet and lifestyle. Our results support the potential utility of the Pls Score as a biomarker for metabolic health and its responsiveness to dietary interventions. Further research is warranted to explore the underlying mechanisms and optimise the practical implementation of the Pls Score in clinical and population settings.
FUNDING
National Health and Medical Research Council (NHMRC grant 233200), National Health and Medical Research Council of Australia (Project grant APP1101320), Health Promotion Foundation of Western Australia, and National Health and Medical Research Council of Australia Senior Research Fellowship (#1042095).
PubMed: 38861870
DOI: 10.1016/j.ebiom.2024.105187 -
Analytical and Bioanalytical Chemistry Jun 2024Plasmalogens are a special class of glycerophospholipids characterized by a vinyl ether bond (-C = C-O-) at the sn-1 position of the glycerol backbone. Altered...
Plasmalogens are a special class of glycerophospholipids characterized by a vinyl ether bond (-C = C-O-) at the sn-1 position of the glycerol backbone. Altered plasmalogen profiles have been observed in neurodegenerative diseases and cancers. Profiling of plasmalogens requires specifying the vinyl ether bond and differentiating them from various types of isobars and isomers. Herein, by coupling C = C derivatization via offline Paternò-Büchi reaction with liquid chromatography-tandem mass spectrometry, we have developed a sensitive workflow for analysis of plasmalogens from biological samples. Using bovine heart lipid extract as a model system, we profiled more than 100 distinct structures of plasmenylethanolamines (PE-Ps) and plasmenylcholines (PC-Ps) at the C = C location level, far exceeding previous reports. Analysis of human glioma and normal brain tissue samples revealed elevated n-10 C = C isomers of PE-Ps in the glioma tissue samples. These findings suggest that the developed workflow holds potential in aiding the study of altered metabolism of plasmalogens in clinical samples.
PubMed: 38861160
DOI: 10.1007/s00216-024-05376-9 -
Journal of the Science of Food and... Jun 2024Lack of n-3 polyunsaturated fatty acids during the period of maternity drastically lowers the docosahexaenoic acid (DHA) level in the brain of offspring and studies have...
Effects of short-term supplementation with DHA-enriched phosphatidylcholine and phosphatidylserine on lipid profiles in the brain and liver of n-3 PUFA-deficient mice in early life after weaning.
BACKGROUND
Lack of n-3 polyunsaturated fatty acids during the period of maternity drastically lowers the docosahexaenoic acid (DHA) level in the brain of offspring and studies have demonstrated that different molecular forms of DHA are beneficial to brain development. The aim of this study was to investigate the effect of short-term supplementation with DHA-enriched phosphatidylserine (PS) and phosphatidylcholine (PC) on DHA levels in the liver and brain of congenital n-3-deficient mice.
RESULTS
Dietary supplementation with DHA significantly changed the fatty acid composition of various phospholipid molecules in the cerebral cortex and liver while DHA-enriched phospholipid was more effective than DHA triglyceride (TG) in increasing brain and liver DHA. Both DHA-PS and DHA-PC could effectively increase the DHA levels, but DHA in the PS form was superior to PC in the contribution of DHA content in the brain ether-linked PC (ePC) and liver lyso-phosphatidylcholine molecular species. DHA-PC showed more significant effects on the increase of DHA in liver TG, PC, ePC, phosphatidylethanolamine (PE) and PE plasmalogen (pPE) molecular species and decreasing the arachidonic acid level in liver PC plasmalogen, ePC, PE and pPE molecular species compared with DHA-PS.
CONCLUSION
The effect of dietary interventions with different molecular forms of DHA for brain and liver lipid profiles is different, which may provide theoretical guidance for dietary supplementation of DHA for people. © 2024 Society of Chemical Industry.
PubMed: 38843481
DOI: 10.1002/jsfa.13625 -
Food Chemistry Oct 2024Milk phospholipids have multiple health benefits, but the deficiency of detailed phospholipid profiles in dairy products brings obstacles to intake calculation and...
Milk phospholipids have multiple health benefits, but the deficiency of detailed phospholipid profiles in dairy products brings obstacles to intake calculation and function evaluation of dairy phospholipids. In present study, 306 phospholipid molecular species were identified and quantified among 207 milk, yogurt and cream products using a HILIC-ESI-Q-TOF MS and a HILIC-ESI-QQQ MS. The phospholipid profiles of five mammals' milk show that camel milk contains the most abundant phosphatidylethanolamine, phosphatidylserine and sphingomyelin; cow, yak and goat milk have similar phospholipidomes, while buffalo milk contains abundant phosphatidylinositol. Fewer plasmalogens but more lyso-glycerolphospholipids were found in ultra-high-temperature (UHT) sterilized milk than in pasteurized milk, and higher proportions of lyso-glycerolphospholipid/total phospholipid were observed in both cream and skimmed/semi-skimmed milk than whole milk, indicating that UHT and skimming processes improve glycerolphospholipid degradation and phospholipid nutrition loss. Meanwhile, more diacyl-glycerolphospholipids and less of their degradation products make yogurt a better phospholipid resource than whole milk.
Topics: Animals; Phospholipids; Milk; Yogurt; Cattle; Food Handling; Goats; Dairy Products; Camelus; Buffaloes
PubMed: 38805923
DOI: 10.1016/j.foodchem.2024.139733 -
Journal of Proteome Research Jun 2024The metabolites and microbiota in tongue coating display distinct characteristics in certain digestive disorders, yet their relationship with colorectal cancer (CRC)...
The metabolites and microbiota in tongue coating display distinct characteristics in certain digestive disorders, yet their relationship with colorectal cancer (CRC) remains unexplored. Here, we employed liquid chromatography coupled with tandem mass spectrometry to analyze the lipid composition of tongue coating using a nontargeted approach in 30 individuals with colorectal adenomas (CRA), 32 with CRC, and 30 healthy controls (HC). We identified 21 tongue coating lipids that effectively distinguished CRC from HC (AUC = 0.89), and 9 lipids that differentiated CRC from CRA (AUC = 0.9). Furthermore, we observed significant alterations in the tongue coating lipid composition in the CRC group compared to HC/CRA groups. As the adenoma-cancer sequence progressed, there was an increase in long-chain unsaturated triglycerides (TG) levels and a decrease in phosphatidylethanolamine plasmalogen (PE-P) levels. Furthermore, we noted a positive correlation between -acyl ornithine (NAOrn), sphingomyelin (SM), and ceramide phosphoethanolamine (PE-Cer), potentially produced by members of the phylum. The levels of inflammatory lipid metabolite 12-HETE showed a decreasing trend with colorectal tumor progression, indicating the potential involvement of tongue coating microbiota and tumor immune regulation in early CRC development. Our findings highlight the potential utility of tongue coating lipid analysis as a noninvasive tool for CRC diagnosis.
Topics: Humans; Colorectal Neoplasms; Lipidomics; Male; Female; Tongue; Middle Aged; Tandem Mass Spectrometry; Phosphatidylethanolamines; Aged; Chromatography, Liquid; Lipids; Triglycerides; Adenoma; Sphingomyelins; 12-Hydroxy-5,8,10,14-eicosatetraenoic Acid; Plasmalogens; Case-Control Studies; Ethanolamines; Ceramides; Adult
PubMed: 38775738
DOI: 10.1021/acs.jproteome.4c00063 -
Food Research International (Ottawa,... Jun 2024The quality of Pacific oyster (Crassostrea gigas) can be affected by many factors during depuration, in which temperature is the major element. In this study, we aim to...
The quality of Pacific oyster (Crassostrea gigas) can be affected by many factors during depuration, in which temperature is the major element. In this study, we aim to determine the quality and plasmalogen changes in C. gigas depurated at different temperatures. The quality was significantly affected by temperature, represented by varying survival rate, glycogen content, total antioxidant capacity, alkaline phosphatase activity between control and stressed groups. Targeted MS analysis demonstrated that plasmalogen profile was significantly changed during depuration with PUFA-containing plasmalogen species being most affected by temperature. Proteomics analysis and gene expression assay further verified that plasmalogen metabolism is regulated by temperature, specifically, the plasmalogen synthesis enzyme EPT1 was significantly downregulated by high temperature and four plasmalogen-related genes (GPDH, PEDS, Pex11, and PLD1) were transcriptionally regulated. The positive correlations between the plasmalogen level and quality characteristics suggested plasmalogen could be regarded as a quality indicator of oysters during depuration.
Topics: Animals; Plasmalogens; Crassostrea; Temperature; Shellfish; Proteomics; Antioxidants; Alkaline Phosphatase; Food Quality
PubMed: 38729722
DOI: 10.1016/j.foodres.2024.114356 -
The Journal of Nutrition May 2024The intake of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) have been associated with health benefits. Blood levels of these fatty acids, measured by gas...
BACKGROUND
The intake of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) have been associated with health benefits. Blood levels of these fatty acids, measured by gas chromatography (GC), are associated with their dietary intake, but the relationships with lipidomic measurements are not well defined.
OBJECTIVES
This study aimed to determine the lipidomic biomarkers in whole blood that predict intakes of EPA + DHA and examine the relationship between lipidomic and GC-based n-3 polyunsaturated fatty acid (n-3 PUFA) biomarkers.
METHODS
Lipidomic and fatty acid analyses were completed on 120 whole blood samples collected from Danish participants. Dietary intakes were completed using a web-based 7-d food diary. Stepwise multiple linear regression was used to identify the fatty acid and lipidomic variables that predict intakes of EPA + DHA and to determine lipidomic species that predict commonly used fatty acid biomarkers.
RESULTS
Stepwise regression selected lipidomic variables with an R = 0.52 for predicting EPA + DHA intake compared to R = 0.40 for the selected fatty acid GC-based variables. More predictive models were generated when the lipidomic variables were selected for females only (R = 0.62, n = 68) and males only (R = 0.72, n = 52). Phosphatidylethanolamine plasmalogen species containing EPA or DHA tended to be the most predictive lipidomic variables. Stepwise regression also indicated that selected lipidomic variables can predict commonly used fatty acid GC-based n-3 PUFA biomarkers as the R values ranged from 0.84 to 0.91.
CONCLUSIONS
Both fatty acid and lipidomic data can be used to predict EPA + DHA intakes, and fatty acid GC-based biomarkers can be emulated by lipidomic species. Lipidomic-based biomarkers appear to be influenced by sex differences, probably in n-3 PUFA and lipoprotein metabolism. These results improve our ability to understand the relationship between novel lipidomic data and GC fatty acid data and will increase our ability to apply lipidomic methods to fatty acid and lipid nutritional research.
PubMed: 38710305
DOI: 10.1016/j.tjnut.2024.04.038 -
Vascular Pharmacology Jun 2024Atherosclerosis is a major cause of ischemic stroke, and early detection of advanced atherosclerosis in the carotid artery is important for reducing morbidity and... (Comparative Study)
Comparative Study
BACKGROUND
Atherosclerosis is a major cause of ischemic stroke, and early detection of advanced atherosclerosis in the carotid artery is important for reducing morbidity and mortality. What is even more important is not only detection of atherosclerosis but early determination whether the patients are at high risk of an event with adverse effects as the size of the plaque does not necessarily reflect its potential to trigger such events.
AIM
We studied whether plasma lipidomics profile can be used as a diagnostic tool for stratification of stable or unstable plaques without the need of removing the carotid plaque.
METHODS
This study used liquid chromatography high-resolution tandem mass spectrometry lipidomics to characterize lipid profiles in patients' plasma and found that patients with significant and complicated (vulnerable) atherosclerotic plaque had distinct lipid profiles compared to those with insignificant plaques.
RESULTS
The lipid classes that were most predictive of vulnerable plaque were lysophosphoethanolamines, fatty acyl esters of hydroxy fatty acids, free fatty acids, plasmalogens, and triacylglycerols. Most of these compounds were found decreased in plasma of patients with unstable plaques which enabled sufficient performance of a statistical model used for patient stratification.
CONCLUSIONS
Plasma lipidomes measured by liquid chromatography-mass spectrometry show differences in patients with stable and unstable carotid plaques, therefore these compounds could potentially be used as biomarkers for unstable plaque in future clinical diagnosis.
Topics: Humans; Lipidomics; Plaque, Atherosclerotic; Male; Female; Aged; Lipids; Carotid Artery Diseases; Biomarkers; Middle Aged; Tandem Mass Spectrometry; Chromatography, Liquid; Predictive Value of Tests; Rupture, Spontaneous; Aged, 80 and over; Case-Control Studies
PubMed: 38705432
DOI: 10.1016/j.vph.2024.107377 -
European Journal of Epidemiology May 2024There is growing interest in incorporating metabolomics into public health practice. However, Black women are under-represented in many metabolomics studies. If...
There is growing interest in incorporating metabolomics into public health practice. However, Black women are under-represented in many metabolomics studies. If metabolomic profiles differ between Black and White women, this under-representation may exacerbate existing Black-White health disparities. We therefore aimed to estimate metabolomic differences between Black and White women in the U.S. We leveraged data from two prospective cohorts: the Nurses' Health Study (NHS; n = 2077) and Women's Health Initiative (WHI; n = 2128). The WHI served as the replication cohort. Plasma metabolites (n = 334) were measured via liquid chromatography-tandem mass spectrometry. Observed metabolomic differences were estimated using linear regression and metabolite set enrichment analyses. Residual metabolomic differences in a hypothetical population in which the distributions of 14 risk factors were equalized across racial groups were estimated using inverse odds ratio weighting. In the NHS, Black-White differences were observed for most metabolites (75 metabolites with observed differences |0.50| standard deviations). Black women had lower average levels than White women for most metabolites (e.g., for N6, N6-dimethlylysine, mean Black-White difference = - 0.98 standard deviations; 95% CI: - 1.11, - 0.84). In metabolite set enrichment analyses, Black women had lower levels of triglycerides, phosphatidylcholines, lysophosphatidylethanolamines, phosphatidylethanolamines, and organoheterocyclic compounds, but higher levels of phosphatidylethanolamine plasmalogens, phosphatidylcholine plasmalogens, cholesteryl esters, and carnitines. In a hypothetical population in which distributions of 14 risk factors were equalized, Black-White metabolomic differences persisted. Most results replicated in the WHI (88% of 272 metabolites available for replication). Substantial differences in metabolomic profiles exist between Black and White women. Future studies should prioritize racial representation.
PubMed: 38703248
DOI: 10.1007/s10654-024-01111-x