The foundations and development of lipidomics

Journal of Lipid Research, Journal Year: 2021, Volume and Issue: 63(2), P. 100164 - 100164

Published: Dec. 22, 2021

For over a century, the importance of lipid metabolism in biology was recognized but difficult to mechanistically understand due lack sensitive and robust technologies for identification quantification molecular species. The enabling technological breakthroughs emerged 1980s with development soft ionization methods (Electrospray Ionization Matrix Assisted Laser Desorption/Ionization) that could identify quantify intact individual These laid foundations what be later named field lipidomics. Further innovative advances multistage fragmentation, dramatic improvements resolution mass accuracy, multiplexed sample analysis fueled early growth lipidomics through 1990s. exponentially grew use variety strategic approaches, which included direct infusion, chromatographic separation, charge-switch derivatization, facilitated access low abundance species lipidome. In this Thematic Review, we provide broad perspective foundations, advances, predicted future directions field.

Language: Английский

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Genome-wide association analysis of plasma lipidome identifies 495 genetic associations

Nature Communications, Journal Year: 2023, Volume and Issue: 14(1)

Published: Oct. 31, 2023

The human plasma lipidome captures risk for cardiometabolic diseases. To discover new lipid-associated variants and understand the link between lipid species disorders, we perform univariate multivariate genome-wide analyses of 179 in 7174 Finnish individuals. We fine-map associated loci, prioritize genes, examine their disease links 377,277 FinnGen participants. identify 495 genome-trait associations 56 genetic loci including 8 novel with a considerable boost provided by analysis. For 26 fine-mapping identifies high causal probability, 14 coding indicating likely genes. A phenome-wide analysis across 953 endpoints reveals 40 loci. 11 coronary artery variants, detect strong species. Our study demonstrates power correlated lipidomics data diseases beyond standard lipids.

Language: Английский

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Comprehensive Metabolic Profiling of Inflammation Indicated Key Roles of Glycerophospholipid and Arginine Metabolism in Coronary Artery Disease

Frontiers in Immunology, Journal Year: 2022, Volume and Issue: 13

Published: March 8, 2022

Background Systemic immune inflammation is a key mediator in the progression of coronary artery disease (CAD), concerning various metabolic and lipid changes. In this study, relationship between inflammatory index profile patients with CAD was investigated to provide deep insights into disturbances related inflammation. Methods Widely targeted plasma metabolomic lipidomic profiling performed 1,234 CAD. Laboratory circulating markers were mainly used define general systemic low-grade states. Multivariable-adjusted linear regression adopted assess associations 860 metabolites 7 markers. Least absolute shrinkage selection operator (LASSO) logistic-based classifiers multivariable logistic applied identify biomarkers states develop models for discriminating an advanced state. Results Multiple species linearly associated seven [false discovery rate (FDR) <0.05]. LASSO multivariable-adjusted analysis identified significant 45 immune-inflammation index, 46 neutrophil–lymphocyte ratio states, 32 score, 26 high-sensitivity C-reactive protein ( P < 0.05). Glycerophospholipid metabolism arginine proline determined as altered pathways Predictive based solely on metabolite combinations showed feasibility (area under curve: 0.81 0.88) four parameters that represent successfully validated using validation cohort. The inflammation-associated metabolite, namely, β-pseudouridine, carotid arteriosclerosis indicators Conclusions This study provides further information profiles represented by These potential pathological changes during may aid development therapeutic targets.

Language: Английский

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Proteomics and lipidomics in atherosclerotic cardiovascular disease risk prediction

European Heart Journal, Journal Year: 2023, Volume and Issue: 44(18), P. 1594 - 1607

Published: March 29, 2023

Given the limited accuracy of clinically used risk scores such as Systematic COronary Risk Evaluation 2 system and Second Manifestations ARTerial disease scores, novel algorithms determining an individual's susceptibility future incident or recurrent atherosclerotic cardiovascular (ASCVD) are urgently needed. Due to major improvements in assay techniques, multimarker proteomic lipidomic panels hold promise be reliably assessed a high-throughput routine. Novel machine learning-based approaches have facilitated use this high-dimensional data resulting from these analyses for ASCVD prediction. More than dozen large-scale retrospective studies using different sets biomarkers statistical methods consistently demonstrated additive prognostic value over traditionally clinical scores. Prospective needed determine utility biomarker panel stratification. When combined with genetic predisposition captured polygenic actual phenotype observed coronary artery imaging, proteomics lipidomics can advance understanding complex multifactorial causes underlying risk.

Language: Английский

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Genetic factors shaping the plasma lipidome and the relations to cardiometabolic risk in children and adolescents

EBioMedicine, Journal Year: 2025, Volume and Issue: 112, P. 105537 - 105537

Published: Jan. 2, 2025

Language: Английский

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Lipidome‐ and Genome‐Wide Study to Understand Sex Differences in Circulatory Lipids

Journal of the American Heart Association, Journal Year: 2022, Volume and Issue: 11(19)

Published: Oct. 4, 2022

Background Despite well‐recognized differences in the atherosclerotic cardiovascular disease risk between men and women, sex factors sex‐specific mechanisms pathophysiology of remain poorly understood. Lipid metabolism plays a central role development disease. Understanding lipids their genetic determinants could provide mechanistic insights into aid precise assessment. Herein, we examined plasma lipidome heterogeneity influences on women through sex‐stratified genome‐wide association analyses. Methods Results We used data consisting 179 lipid species measured by shotgun lipidomics 7266 individuals from Finnish GeneRISK cohort sought for replication using independent 2045 participants. Significant levels 141 were observed ( P <7.0×10 −4 ). Interestingly, 121 showed significant age‐sex interactions, with opposite age‐related changes 39 species. In general, most cholesteryl esters, ceramides, lysophospholipids, glycerides higher 45‐ to 50‐year‐old compared same age, but narrowed down or reversed age. did not observe any major effect analyses, which suggests that common variants do have lipidome. Conclusions Our study provides comprehensive view circulatory pointing potential highlights need sex‐ age‐specific prevention strategies.

Language: Английский

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Oxidative Stress, Atherogenic Dyslipidemia, and Cardiovascular Risk

Biomedicines, Journal Year: 2023, Volume and Issue: 11(11), P. 2897 - 2897

Published: Oct. 26, 2023

Oxidative stress is the consequence of an overproduction reactive oxygen species (ROS) that exceeds antioxidant defense mechanisms. Increased levels ROS contribute to development cardiovascular disorders through oxidative damage macromolecules, particularly by oxidation plasma lipoproteins. One most prominent features atherogenic dyslipidemia accumulation small dense LDL (sdLDL) particles, characterized increased susceptibility oxidation. Indeed, a considerable and diverse body evidence from animal models epidemiological studies was generated supporting modification sdLDL particles as earliest event in atherogenesis. Lipid peroxidation results formation various bioactive atherosclerotic process different pathophysiological mechanisms, including foam cell formation, direct detrimental effects, receptor-mediated activation pro-inflammatory signaling pathways. In this paper, we will discuss recent data on role their interplay atherosclerosis. addition, special focus be placed clinical applicability novel, promising biomarkers these processes.

Language: Английский

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Lipidomic risk scores are independent of polygenic risk scores and can predict incidence of diabetes and cardiovascular disease in a large population cohort

PLoS Biology, Journal Year: 2022, Volume and Issue: 20(3), P. e3001561 - e3001561

Published: March 3, 2022

Type 2 diabetes (T2D) and cardiovascular disease (CVD) represent significant burdens for most societies susceptibility to these diseases is strongly influenced by diet lifestyle. Physiological changes associated with T2D or CVD, such has high blood pressure cholesterol glucose levels in the blood, are often apparent prior incidence. Here we integrated genetics, lipidomics, standard clinical diagnostics assess future CVD risk 4,067 participants from a large prospective population-based cohort, Malmö Diet Cancer-Cardiovascular Cohort. By training Ridge regression-based machine learning models on measurements obtained at baseline when individuals were healthy, computed several scores incidence during up 23 years of follow-up. We used stratify into groups found that lipidomics score based quantification 184 plasma lipid concentrations resulted 168% 84% increase rate highest group 77% 53% decrease lowest respectively, compared average case rates 13.8% 22.0%. Notably, lipidomic correlated only marginally polygenic risk, indicating lipidome genetic variants may constitute largely independent factors CVD. Risk stratification was further improved adding variables model, resulting 51.0% 53.3% respectively. The showed significantly altered compositions affecting 167 157 species Our results demonstrated subset developing can be identified before which derived one single mass spectrometric measurement cheap fast, informative could extend traditional assessment assays.

Language: Английский

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The biomarkers discovery of hyperuricemia and gout: proteomics and metabolomics

PeerJ, Journal Year: 2022, Volume and Issue: 11, P. e14554 - e14554

Published: Jan. 6, 2022

Background Hyperuricemia and gout are a group of disorders purine metabolism. In recent years, the incidence hyperuricemia has been increasing, which is severe threat to people’s health. Several studies on in proteomics metabolomics have conducted recently. Some literature identified biomarkers that distinguish asymptomatic from acute or remission gout. We summarize physiological processes these may be involved their role disease progression. Methodology used professional databases including PubMed, Web Science conduct review. This review addresses current landscape with focus metabolomics. Results Proteomic methods identify differentially expressed proteins find specific biomarkers. These findings suggestive for diagnosis treatment explore pathogenesis. The mediators link between hyperuricemia, kidney disease, metabolic syndrome, diabetes hypertriglyceridemia. Metabolomics reveals main influential pathways through small molecule metabolites, such as amino acid metabolism, lipid other characteristic pathways. contributed discovery Chinese medicine. traditional medicine compounds can improve disease. Conclusions suggest some possible relationships potential inflammatory episodes, complement activation, able different stages development. However, there relatively few proteomic well metabolomic gout, experiments only primary screening tests, need further in-depth study.

Language: Английский

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Effect of biological sex on human circulating lipidome: An overview of the literature

Atherosclerosis, Journal Year: 2023, Volume and Issue: 384, P. 117274 - 117274

Published: Sept. 22, 2023

Cardiovascular diseases (CVD) are the leading cause of death worldwide for both men and women, but their prevalence burden show marked sex differences. The existing knowledge gaps in research, prevention, treatment women emphasize need understanding biological mechanisms contributing to differences CVD. Sex plasma lipids that well-known risk factors predictors CVD events have been recognized believed contribute known disparities manifestations women. However, current has mainly come from studies on routinely measured standard lipids- low-density lipoprotein cholesterol (LDL-C), high-density (HDL-C), total triglycerides, cholesterol, which mainstay lipid profiling. individual species, collectively called lipidome, until recently less explored due technological challenges analytic costs. With advancements last decade growing interest sexual dimorphism metabolic disorders, many investigators utilized metabolomics lipidomics based platforms examine effect detailed lipidomic profiles species. This review presents an overview research concentrations circulating focusing findings metabolome- lipidome-wide studies. We also discuss potential contribution genetic including chromosomes sex-specific physiological such as menopause hormones profiles.

Language: Английский

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