ORCID Profile
0000-0002-6050-1259
Current Organisations
UNSW Australia
,
Baker IDI Heart and Diabetes Institute
,
Curtin University
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Proteomics and metabolomics | Bioinformatics and computational biology | Systems biology | Genomics
Publisher: Elsevier BV
Date: 12-2021
Publisher: MDPI AG
Date: 21-09-2021
Abstract: Lipid metabolism is tightly linked to adiposity. Comprehensive lipidomic profiling offers new insights into the dysregulation of lipid metabolism in relation to weight gain. Here, we investigated the relationship of the human plasma lipidome and changes in waist circumference (WC) and body mass index (BMI). Adults (2653 men and 3196 women), 25–95 years old who attended the baseline survey of the Australian Diabetes, Obesity and Lifestyle Study (AusDiab) and the 5-year follow-up were enrolled. A targeted lipidomic approach was used to quantify 706 distinct molecular lipid species in the plasma s les. Multiple linear regression models were used to examine the relationship between the baseline lipidomic profile and changes in WC and BMI. Metabolic scores for change in WC were generated using a ridge regression model. Alkyl-diacylglycerol such as TG(O-50:2) [NL-18:1] displayed the strongest association with change in WC (β-coefficient = 0.125 cm increment per SD increment in baseline lipid level, p = 2.78 × 10−11. Many lipid species containing linoleate (18:2) fatty acids were negatively associated with both WC and BMI gain. Compared to traditional models, multivariate models containing lipid species identify in iduals at a greater risk of gaining WC: top quintile relative to bottom quintile (odds ratio, 95% CI = 5.4, 3.8–6.6 for women and 2.3, 1.7–3.0 for men). Our findings define metabolic profiles that characterize in iduals at risk of weight gain or WC increase and provide important insight into the biological role of lipids in obesity.
Publisher: Institute of Electrical and Electronics Engineers (IEEE)
Date: 02-2020
Publisher: Elsevier BV
Date: 07-2022
DOI: 10.1016/J.PLIPRES.2022.101177
Abstract: Large 'omics studies are of particular interest to population and clinical research as they allow elucidation of biological pathways that are often out of reach of other methodologies. Typically, these information rich datasets are produced from multiple coordinated profiling studies that may include lipidomics, metabolomics, proteomics or other strategies to generate high dimensional data. In lipidomics, the generation of such data presents a series of unique technological and logistical challenges to maximize the power (number of s les) and coverage (number of analytes) of the dataset while minimizing the sources of unwanted variation. Technological advances in analytical platforms, as well as computational approaches, have led to improvement of data quality - especially with regard to instrumental variation. In the small scale, it is possible to control systematic bias from beginning to end. However, as the size and complexity of datasets grow, it is inevitable that unwanted variation arises from multiple sources, some potentially unknown and out of the investigators control. Increases in cohort size and complexity have led to new challenges in s le collection, handling, storage, and preparation. If not considered and dealt with appropriately, this unwanted variation may undermine the quality of the data and reliability of any subsequent analysis. Here we review the various experimental phases where unwanted variation may be introduced and review general strategies and approaches to handle this variation, specifically addressing issues relevant to lipidomics studies.
Publisher: Wiley
Date: 20-07-2016
DOI: 10.1111/JMI.12446
Abstract: Semiquantitative immunofluorescence microscopy has become a key methodology in biomedical research. Typical statistical workflows are considered in the context of avoiding pseudo-replication and marginalising experimental error. However, immunofluorescence microscopy naturally generates hierarchically structured data that can be leveraged to improve statistical power and enrich biological interpretation. Herein, we describe a robust distribution fitting procedure and compare several statistical tests, outlining their potential advantages/disadvantages in the context of biological interpretation. Further, we describe tractable procedures for power analysis that incorporates the underlying distribution, s le size and number of images captured per s le. The procedures outlined have significant potential for increasing understanding of biological processes and decreasing both ethical and financial burden through experimental optimization.
Publisher: Springer Science and Business Media LLC
Date: 03-06-2014
Publisher: The Endocrine Society
Date: 04-02-2020
Abstract: Insulin resistance (IR) remains a global health challenge. Lipidomics offers an opportunity to identify biomarkers and better understand mechanisms of IR associated with abnormal lipid metabolism. The objective of this article is to determine plasma lipid species associated with indices of IR and evaluate the lipidome response to an oral glucose tolerance test (OGTT). This study was community based and cross-sectional. Plasma s les (collected at 0 and 120 min during an OGTT) from nonobese, young adults age 18 to 34 years (n = 246) were analyzed using liquid chromatography–tandem mass spectrometry. The associations between indices of IR and lipid classes and species (with a sex interaction term), or changes in lipid levels during an OGTT, were tested using linear models (adjusted for age, sex, body mass index, total cholesterol, high-density lipoprotein cholesterol, and triglycerides). Some (213) and (199) lipid species were associated with the homeostatic model assessment of insulin resistance and insulin area under curve (AUC), respectively. Alkylphosphatidylcholine (10), alkenylphosphatidylcholine (23), and alkylphosphatidylethanolamine (6) species were associated with insulin AUC in men only. Species of phosphatidylcholine (7) and sphingomyelin (5) were associated in women only. In response to an OGTT, a perturbation in the plasma lipidome, particularly in acylcarnitine species, was observed and the changes in many lipid species were associated with insulin AUC. The plasma lipidome and changes in lipid levels during an OGTT were associated with indices of IR. These findings underlie the involvement of molecular lipid species in the pathogenesis of IR and possibly crosstalk between IR and sex-specific regulation of lipid metabolism.
Publisher: Springer US
Date: 2023
Publisher: Elsevier BV
Date: 09-2018
DOI: 10.1016/J.CELREP.2018.08.017
Abstract: Exercise-induced heart growth provides protection against cardiovascular disease, whereas disease-induced heart growth leads to heart failure. These distinct forms of growth are associated with different molecular profiles (e.g., mRNAs, non-coding RNAs, and proteins), and targeting differentially regulated genes has therapeutic potential for heart failure. The effects of exercise on the cardiac and circulating lipidomes in comparison to disease are unclear. Lipidomic profiling was performed on hearts and plasma of mice subjected to swim endurance training or a cardiac disease model (moderate or severe pressure overload). Several sphingolipid species and phospholipids containing omega-3/6 fatty acids were distinctly altered in heart and/or plasma with exercise versus pressure overload. A subset of lipids was validated in an independent mouse model with heart failure and atrial fibrillation. This study highlights the adaptations that occur to lipid profiles in response to endurance training versus pathology and provides a resource to investigate potential therapeutic targets and biomarkers.
Publisher: eLife Sciences Publications, Ltd
Date: 02-03-2022
DOI: 10.7554/ELIFE.72779
Abstract: There is mounting evidence that in utero and early life exposures may predispose an in idual to metabolic disorders in later life and dysregulation of lipid metabolism is critical in such outcomes. However, there is limited knowledge about lipid metabolism and factors causing lipid dysregulation in early life that could result in adverse health outcomes in later life. We studied the effect of antenatal factors such as gestational age, birth weight, and mode of birth on lipid metabolism at birth changes in the circulating lipidome in the first 4 years of life and the effect of breastfeeding in the first year of life. From this study, we aim to generate a framework for deeper understanding into factors effecting lipid metabolism in early life, to provide early interventions for those at risk of developing metabolic disorders including cardiovascular diseases. We performed comprehensive lipid profiling of 1074 mother-child dyads in the Barwon Infant Study (BIS), a population-based pre-birth cohort and measured 776 distinct lipid features across 39 lipid classes using ultra-high-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS). We measured lipids in 1032 maternal serum s les at 28 weeks’ gestation, 893 cord serum s les at birth, 793, 735, and 511 plasma s les at 6, 12 months, and 4 years, respectively. Cord serum was enriched with long chain poly-unsaturated fatty acids (LC-PUFAs), and corresponding cholesteryl esters relative to the maternal serum. We performed regression analyses to investigate the associations of cord serum lipid species with antenatal factors: gestational age, birth weight, mode of birth and duration of labour. The lipidome differed between mother and newborn and changed markedly with increasing child’s age. Alkenylphosphatidylethanolamine species containing LC-PUFAs increased with child’s age, whereas the corresponding lysophospholipids and triglycerides decreased. Majority of the cord serum lipids were strongly associated with gestational age and birth weight, with most lipids showing opposing associations. Each mode of birth showed an independent association with cord serum lipids. Breastfeeding had a significant impact on the plasma lipidome in the first year of life, with up to 17-fold increases in a few species of alkyldiaclylglycerols at 6 months of age. This study sheds light on lipid metabolism in infancy and early childhood and provide a framework to define the relationship between lipid metabolism and health outcomes in early childhood. This work was supported by the A*STAR-NHMRC joint call funding (1711624031).
Publisher: Public Library of Science (PLoS)
Date: 12-2016
Publisher: Frontiers Media SA
Date: 24-07-2017
Publisher: Springer Science and Business Media LLC
Date: 07-03-2015
Publisher: eLife Sciences Publications, Ltd
Date: 31-03-2023
DOI: 10.7554/ELIFE.86139
Abstract: Cardiometabolic diseases encompass a range of interrelated conditions that arise from underlying metabolic perturbations precipitated by genetic, environmental, and lifestyle factors. While obesity, dyslipidaemia, smoking, and insulin resistance are major risk factors for cardiometabolic diseases, in iduals still present in the absence of such traditional risk factors, making it difficult to determine those at greatest risk of disease. Thus, it is crucial to elucidate the genetic, environmental, and molecular underpinnings to better understand, diagnose, and treat cardiometabolic diseases. Much of this information can be garnered using systems genetics, which takes population-based approaches to investigate how genetic variance contributes to complex traits. Despite the important advances made by human genome-wide association studies (GWAS) in this space, corroboration of these findings has been h ered by limitations including the inability to control environmental influence, limited access to pertinent metabolic tissues, and often, poor classification of diseases or phenotypes. A complementary approach to human GWAS is the utilisation of model systems such as genetically erse mouse panels to study natural genetic and phenotypic variation in a controlled environment. Here, we review mouse genetic reference panels and the opportunities they provide for the study of cardiometabolic diseases and related traits. We discuss how the post-GWAS era has prompted a shift in focus from discovery of novel genetic variants to understanding gene function. Finally, we highlight key advantages and challenges of integrating complementary genetic and multi-omics data from human and mouse populations to advance biological discovery.
Publisher: Springer Science and Business Media LLC
Date: 25-07-2022
DOI: 10.1186/S12916-022-02432-Y
Abstract: Lipids play a vital role in health and disease, but changes to their circulating levels and the link with obesity remain poorly characterized in expecting mothers and their offspring in early childhood. LC-MS/MS-based quantitation of 480 lipid species was performed on 2491 plasma s les collected at 4 time points in the mother-offspring Asian cohort GUSTO (Growing Up in Singapore Towards healthy Outcomes). These 4 time points constituted s les collected from mothers at 26–28 weeks of gestation ( n =752) and 4–5 years postpartum ( n =650), and their offspring at birth ( n =751) and 6 years of age ( n =338). Linear regression models were used to identify the pregnancy and developmental age-specific variations in the plasma lipidomic profiles, and their association with obesity risk. An independent birth cohort ( n =1935), the Barwon Infant Study (BIS), comprising mother-offspring dyads of Caucasian origin was used for validation. Levels of 36% of the profiled lipids were significantly higher (absolute fold change 1.5 and P adj 0.05) in antenatal maternal circulation as compared to the postnatal phase, with phosphatidylethanolamine levels changing the most. Compared to antenatal maternal lipids, cord blood showed lower concentrations of most lipid species (79%) except lysophospholipids and acylcarnitines. Changes in lipid concentrations from birth to 6 years of age were much higher in magnitude (log 2 FC=−2.10 to 6.25) than the changes observed between a 6-year-old child and an adult (postnatal mother) (log 2 FC=−0.68 to 1.18). Associations of cord blood lipidomic profiles with birth weight displayed distinct trends compared to the lipidomic profiles associated with child BMI at 6 years. Comparison of the results between the child and adult BMI identified similarities in association with consistent trends ( R 2 =0.75). However, large number of lipids were associated with BMI in adults (67%) compared to the children (29%). Pre-pregnancy BMI was specifically associated with decrease in the levels of phospholipids, sphingomyelin, and several triacylglycerol species in pregnancy. In summary, our study provides a detailed landscape of the in utero lipid environment provided by the gestating mother to the growing fetus, and the magnitude of changes in plasma lipidomic profiles from birth to early childhood. We identified the effects of adiposity on the circulating lipid levels in pregnant and non-pregnant women as well as offspring at birth and at 6 years of age. Additionally, the pediatric vs maternal overlap of the circulating lipid phenotype of obesity risk provides intergenerational insights and early opportunities to track and intervene the onset of metabolic adversities. This birth cohort is a prospective observational study, which was registered on 1 July 2010 under the identifier NCT01174875 .
Publisher: MDPI AG
Date: 25-05-2021
Abstract: Statins are the first-line lipid-lowering therapy for reducing cardiovascular disease (CVD) risk. A plasma lipid ratio of two phospholipids, PI(36:2) and PC(18:0_20:4), was previously identified to explain 58% of the relative CVD risk reduction associated with pravastatin, independent of a change in low-density lipoprotein-cholesterol. This ratio may be a potential biomarker for the treatment effect of statins however, the underlying mechanisms linking this ratio to CVD risk remain unclear. In this study, we investigated the effect of altered cholesterol conditions on the lipidome of cultured human liver cells (Hep3B). Hep3B cells were treated with simvastatin (5 μM), cyclodextrin (20 mg/mL) or cholesterol-loaded cyclodextrin (20 mg/mL) for 48 h and their lipidomes were examined. Induction of a low-cholesterol environment via simvastatin or cyclodextrin was associated with elevated levels of lipids containing arachidonic acid and decreases in phosphatidylinositol species and the PI(36:2)/PC(18:0_20:4) ratio. Conversely, increasing cholesterol levels via cholesterol-loaded cyclodextrin resulted in reciprocal regulation of these lipid parameters. Expression of genes involved in cholesterol and fatty acid synthesis supported the lipidomics data. These findings demonstrate that the PI(36:2)/PC(18:0_20:4) ratio responds to changes in intracellular cholesterol abundance per se, likely through a flux of the n-6 fatty acid pathway and altered phosphatidylinositol synthesis. These findings support this ratio as a potential marker for CVD risk reduction and may be useful in monitoring treatment response.
Publisher: Institute of Electrical and Electronics Engineers (IEEE)
Date: 11-2017
Publisher: Frontiers Media SA
Date: 2013
Publisher: Springer Science and Business Media LLC
Date: 06-06-2022
DOI: 10.1038/S41467-022-30875-7
Abstract: We integrated lipidomics and genomics to unravel the genetic architecture of lipid metabolism and identify genetic variants associated with lipid species putatively in the mechanistic pathway for coronary artery disease (CAD). We quantified 596 lipid species in serum from 4,492 in iduals from the Busselton Health Study. The discovery GWAS identified 3,361 independent lipid-loci associations, involving 667 genomic regions (479 previously unreported), with validation in two independent cohorts. A meta-analysis revealed an additional 70 independent genomic regions associated with lipid species. We identified 134 lipid endophenotypes for CAD associated with 186 genomic loci. Associations between independent lipid-loci with coronary atherosclerosis were assessed in ∼456,000 in iduals from the UK Biobank. Of the 53 lipid-loci that showed evidence of association ( P 1 × 10 −3 ), 43 loci were associated with at least one lipid endophenotype. These findings illustrate the value of integrative biology to investigate the aetiology of atherosclerosis and CAD, with implications for other complex diseases.
Publisher: Springer Science and Business Media LLC
Date: 10-11-2020
DOI: 10.1038/S41467-020-19473-7
Abstract: Changes to lipid metabolism are tightly associated with the onset and pathology of Alzheimer’s disease (AD). Lipids are complex molecules comprising many isomeric and isobaric species, necessitating detailed analysis to enable interpretation of biological significance. Our expanded targeted lipidomics platform (569 species across 32 classes) allows for detailed lipid separation and characterisation. In this study we examined peripheral s les of two cohorts (AIBL, n = 1112 and ADNI, n = 800). We are able to identify concordant peripheral signatures associated with prevalent AD arising from lipid pathways including ether lipids, sphingolipids (notably GM 3 gangliosides) and lipid classes previously associated with cardiometabolic disease (phosphatidylethanolamine and triglycerides). We subsequently identified similar lipid signatures in both cohorts with future disease. Lastly, we developed multivariate lipid models that improved classification and prediction. Our results provide a holistic view between the lipidome and AD using a comprehensive approach, providing targets for further mechanistic investigation.
Publisher: Wiley
Date: 30-01-2014
DOI: 10.1002/JAT.2985
Abstract: Epidemiological studies indicate that exposure to diesel exhaust (DE) is associated with vascular-based disorders. To investigate the effect of DE on blood-brain barrier (BBB) function and integrity, 8-week-old BALB/c mice were randomized to DE in a cyclical treatment regimen over a 2-week period. Functional integrity of BBB was determined by considering brain parenchymal abundance of IgG within the hippoc al formation and cortex at 6 h and 24 h intervals following final exposure treatment. Neurovascular inflammation was expressed as the abundance of glial fibrillar acidic protein. Two doses of DE were studied and compared to air-only treated mice. Mice exposed to DE had substantially greater abundance of parenchymal IgG compared to control mice not exposed to DE. Increased parenchymal glial fibrillar acidic protein at 24 h post-DE exposure suggested heightened neurovascular inflammation. Our findings are proof-of-concept that inhalation of DE can compromise BBB function and support the broader contention that DE exposure may contribute to neurovascular disease risk.
Publisher: Springer Science and Business Media LLC
Date: 07-10-2023
Publisher: Cold Spring Harbor Laboratory
Date: 28-05-2020
DOI: 10.1101/2020.05.26.20114215
Abstract: Changes to lipid metabolism are tightly associated with the onset and pathology of Alzheimer’s disease (AD). Lipids are complex molecules comprising of many isomeric and isobaric species, necessitating detailed analysis to enable interpretation of biological significance. Our expanded targeted lipidomics platform (569 lipid species across 32 lipid (sub)classes) allows for detailed isomeric and isobaric lipid separation. We applied the methodology to examine plasma s les from the Australian Imaging, Biomarkers and Lifestyle flagship study of aging (AIBL, n = 1112) and serum from the Alzheimer’s Disease Neuroimaging Initiative (ADNI, n = 800) studies. Cross sectional analysis using both cohorts identified concordant unique peripheral signatures associated with AD. Specific pathways include sphingolipids, including G M3 gangliosides, where their acyl composition drove the major associations, and lipids previously associated with dysfunctional lipid metabolism in cardiometabolic disease including the phosphatidylethanolamine and triglyceride classes. Infomation derived from improved isomeric seperation highlighted pathway-specific changes with ether lipids including plasmalogens implicating perixosmal dysfunction in disease pathology. Longitudinal analysis revealed similar lipid signitures in both AIBL and ADNI cohorts with future disease onset. We utilised the two independent studies to train and validate multivariate lipid models that significantly improved disease classification and prediction. Together our results provide a holistic view of the lipidome and its relationship with AD using a comprehensive lipidomics approach, providing targets for further mechanistic investigation.
Publisher: Oxford University Press (OUP)
Date: 05-03-2015
DOI: 10.1093/NTR/NTV044
Abstract: Emerging evidence suggests that integrity of blood-brain barrier (BBB) is pivotal to pathology and pathogenesis of vascular-based neurodegenerative disorders. We have recently reported BBB protective effects of nutraceutical agents with anti-inflammatory properties in an established dietary-induced BBB dysfunction model. Studies also reported that nicotine exhibits anti-oxidative/-inflammatory effects and improve cognitive impairment in Alzheimer's disease. However there has been no studies reporting the effect of nicotine on high-fat-induced BBB dysfunction. In the present study, we investigated the effect of nicotine on BBB integrity and neuro-inflammation in an established mouse model of BBB disruption induced by a diet enriched in saturated fatty acids (SFA). Wild-type C57BL/6J mice were fed chow enriched in SFA (23% w/w) with/without nicotine for 10 weeks. Compared to mice maintained on SFA-free and low-fat (LF) chow (4% w/w), capillary permeability indicated by the parenchymal extravasation of plasma derived IgG, was significantly greater in the SFA treatment group. Nicotine provided concomitantly with the SFA diet significantly attenuated IgG extravasation, however it remained significantly greater than LF-controls. Markers of neurovascular inflammation glial fibrillary acidic protein, cyclooxygenase-2, and glucose regulated protein 78 remained exaggerated in SFA+nicotine treated mice compared to LF-controls. Nicotine did however modestly, but not significantly, improve plasma total anti-oxidative status in SFA fed mice. Nicotine moderately attenuated BBB disruption induced by chronic ingestion of high-SFA diet, but had no significant effect on neuroinflammation per se.
Publisher: Research Square Platform LLC
Date: 21-04-2023
DOI: 10.21203/RS.3.RS-2809465/V1
Abstract: Obesity is a risk factor for type 2 diabetes and cardiovascular disease. However, a substantial proportion of patients with these conditions have a seemingly normal body mass index (BMI). Conversely, not all obese in iduals present with metabolic disorders giving rise to the concept of “metabolically healthy obese”. Using comprehensive lipidomic datasets from two large independent population cohorts in Australia (n = 14,831), we developed models that predicted BMI and calculated a metabolic BMI score (mBMI) as a measure of metabolic dysregulation associated with obesity. We postulated that the mBMI score would be an independent metric for defining obesity and help identify a hidden risk for metabolic disorders regardless of the measured BMI. Based on the difference between mBMI and BMI (mBMI delta “mBMIΔ”), we identified in iduals with a similar BMI but differing in their metabolic health profiles. Participants in the top quintile of mBMIΔ (Q5) were more than four times more likely to be newly diagnosed with T2DM (OR = 4.5 95% CI = 3.1–6.6), more than two times more likely to develop T2DM over a five year follow up period (OR = 2.5 CI = 1.5–4.1) and had higher odds of cardiovascular disease (heart attack or stroke) (OR = 2.1 95% CI = 1.5–3.1) relative to those in the bottom quintile (Q1). Exercise and diet were associated with mBMIΔ suggesting the ability to modify mBMI with lifestyle intervention. In conclusion, our findings show that, the mBMI score captures information on metabolic dysregulation that is independent of the measured BMI and so provides an opportunity to assess metabolic health to identify in iduals at risk for targeted intervention and monitoring.
Publisher: Cold Spring Harbor Laboratory
Date: 20-06-2023
DOI: 10.1101/2023.06.13.23291049
Abstract: Alzheimer’s disease (AD) is a major neurodegenerative disorder with significant environmental factors, including diet and lifestyle, influencing its onset and progression. Although previous studies have suggested that certain diets may reduce the incidence of AD, the underlying mechanisms remain unclear. In this randomized crossover study of 20 elderly adults, we investigated the effects of a modified Mediterranean ketogenic diet (MMKD) on the plasma lipidome, analyzing 784 lipid species across 47 classes. We identified substantial changes in response to intervention, notably a global elevation across all plasmanyl and plasmenyl ether lipid species among others, with many changes linked with changes to clinical and biochemical markers of AD. Leveraging our prior clinical studies on AD (n = 1,912), we found that MMKD was inversely associated with the lipidomic signature of prevalent and incident AD. Given its low risk and cost, MMKD could be a promising approach for prevention or early symptomatic treatment of AD.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 04-06-2019
Abstract: Although acute coronary syndromes (ACS) are a major cause of morbidity and mortality, relationships with biologically active lipid species potentially associated with plaque disruption/erosion in the context of their lipoprotein carriers are indeterminate. The aim was to characterize lipid species within lipoprotein particles which differentiate ACS from stable coronary artery disease. Venous blood was obtained from 130 in iduals with de novo presentation of an ACS (n=47) or stable coronary artery disease (n=83) before coronary catheterization. Lipidomic measurements (533 lipid species liquid chromatography electrospray ionization/tandem mass spectrometry) were performed on whole plasma as well as 2 lipoprotein subfractions: apolipoprotein A1 (apolipoprotein A, high‐density lipoprotein) and apolipoprotein B. Compared with stable coronary artery disease, ACS plasma was lower in phospholipids including lyso species and plasmalogens, with the majority of lipid species differing in abundance located within high‐density lipoprotein (high‐density lipoprotein, 113 lipids plasma, 73 lipids). Models including plasma lipid species alone improved discrimination between the stable and ACS groups by 0.16 (C‐statistic) compared with conventional risk factors. Models utilizing lipid species either in plasma or within lipoprotein fractions had a similar ability to discriminate groups, though the C‐statistic was highest for plasma lipid species (0.80 95% CI, 0.75–0.86). Multiple lysophospholipids, but not cholesterol, featured among the lipids which were present at low concentration within high‐density lipoprotein of those presenting with ACS. Lipidomics, when applied to either whole plasma or lipoprotein fractions, was superior to conventional risk factors in discriminating ACS from stable coronary artery disease. These associative mechanistic insights elucidate potential new preventive, prognostic, and therapeutic avenues for ACS which require investigation in prospective analyses.
Publisher: Elsevier BV
Date: 07-2018
DOI: 10.1016/J.PLIPRES.2018.06.003
Abstract: Recent advances in analytical techniques have greatly enhanced the depth of coverage, however lipidomic studies are still restricted to analysing only a subset of known lipids. Numerous complementary techniques are used for investigation of cellular lipidomes, including mass spectrometry (MS), nuclear magnetic resonance and vibrational spectroscopy. The development in electrospray ionization (ESI) MS has accelerated lipidomics research in the past two decades and represents one of the most widely used technique. The versatility of ESI-MS systems allows development of methods to detect and quantify a large ersity of lipid species and classes. However, highly targeted and specific approaches can preclude global analysis of many lipid classes. Indeed, experimental procedures are generally optimised for the lipid species, or lipid class of interest. Therefore, careful consideration of experimental procedures is required for characterisation of biological lipidomes. The current review will describe the lipidomic approaches for considering tissue lipid physiology. Discussion of the main sequences in a lipidomics workflow will be presented, including preparation of s les, accurate quantitation of lipid species and statistical modelling.
Publisher: American Society for Clinical Investigation
Date: 06-09-2018
Publisher: MDPI AG
Date: 31-05-2023
DOI: 10.3390/BIOM13060917
Abstract: The current coronary artery disease (CAD) risk scores for predicting future cardiovascular events rely on well-recognized traditional cardiovascular risk factors derived from a population level but often fail in iduals, with up to 25% of first-time heart attack patients having no risk factors. Non-invasive imaging technology can directly measure coronary artery plaque burden. With an advanced lipidomic measurement methodology, for the first time, we aim to identify lipidomic biomarkers to enable intervention before cardiovascular events. With 994 participants from BioHEART-CT Discovery Cohort, we collected clinical data and performed high-performance liquid chromatography with mass spectrometry to determine concentrations of 683 plasma lipid species. Statin-naive participants were selected based on subclinical CAD (sCAD) categories as the analytical cohort (n = 580), with sCAD+ (n = 243) compared to sCAD− (n = 337). Through a machine learning approach, we built a lipid risk score (LRS) and compared the performance of the existing Framingham Risk Score (FRS) in predicting sCAD+. We obtained in idual classifiability scores and determined Body Mass Index (BMI) as the modifying variable. FRS and LRS models achieved similar areas under the receiver operating characteristic curve (AUC) in predicting the validation cohort. LRS enhanced the prediction of sCAD+ in the healthy-weight group (BMI 25 kg/m2), where FRS performed poorly and identified in iduals at risk that FRS missed. Lipid features have strong potential as biomarkers to predict CAD plaque burden and can identify residual risk not captured by traditional risk factors/scores. LRS compliments FRS in prediction and has the most significant benefit in healthy-weight in iduals.
Publisher: MDPI AG
Date: 28-09-2020
Abstract: Brown adipose tissue (BAT) activation is a possible therapeutic strategy to increase energy expenditure and improve metabolic homeostasis in obesity. Recent studies have revealed novel interactions between BAT and circulating lipid species—in particular, the non-esterified fatty acid (NEFA) and oxylipin lipid classes. This study aimed to identify in idual lipid species that may be associated with cold-stimulated BAT activity in humans. A panel of 44 NEFA and 41 oxylipin species were measured using mass-spectrometry-based lipidomics in the plasma of fourteen healthy male participants before and after 90 min of mild cold exposure. Lipid measures were correlated with BAT activity measured via 18F-fluorodeoxyglucose ([18F]FDG) positron emission tomography/computed tomography (PET/CT), along with norepinephrine (NE) concentration (a surrogate marker of sympathetic activity). The study identified a significant increase in total NEFA concentration following cold exposure that was positively associated with NE concentration change. In idually, 33 NEFA and 11 oxylipin species increased significantly in response to cold exposure. The concentration of the omega-3 NEFA, docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) at baseline was significantly associated with BAT activity, and the cold-induced change in 18 NEFA species was significantly associated with BAT activity. No significant associations were identified between BAT activity and oxylipins.
Publisher: S. Karger AG
Date: 02-11-2012
DOI: 10.1159/000343211
Abstract: b i Background: /i /b Disturbances in blood-brain barrier (BBB) integrity contribute to the onset and progression of neurodegenerative diseases including Alzheimer's disease (AD) and vascular dementia (VaD). Aging is positively associated with AD and VaD risk, but this may reflect comorbidities or the effects of other chronic modulators of vascular function such as diet. b i Objective: /i /b To explore putative synergistic effects of aging with diet, in this study genetically unmanipulated mice were maintained on diets enriched in saturated fatty acids (SFA) or cholesterol and compared to mice provided with low-fat (LF) feed formula. b i Methods: /i /b The functional integrity of the BBB was assessed following 3, 6 and 12 months of dietary intervention commenced at 6 weeks of age, by determining the brain parenchymal extravasation of immunoglobulin G (IgG). b i Results: /i /b Mice maintained on the SFA- or cholesterol-enriched diet showed significant parenchymal IgG abundance following 3 months of feeding, concomitant with diminished expression of the tight junction protein occludin. LF control mice had essentially no evidence of BBB disturbances. Six months of SFA feeding exacerbated the difference in IgG abundance compared to the LF mice. At 12 months of feeding, the control LF mice also had significant parenchymal IgG that was comparable to mice fed the SFA- or cholesterol-enriched diet for 3 months. However, there may have been an adaptation to the fat-enriched diets because SFA and cholesterol did not exacerbate IgG parenchymal accumulation beyond 6 months of feeding. b i Conclusion: /i /b Collectively, the study suggests that diets enriched in SFA or cholesterol accelerate the onset of BBB dysfunction that otherwise occurs with aging.
Publisher: Springer Science and Business Media LLC
Date: 27-02-2017
DOI: 10.1038/IJO.2017.57
Abstract: While vascular risk factors including Western-styled diet and obesity are reported to induce cognitive decline and increase dementia risk, recent reports consistently suggest that compromised integrity of cerebrovascular blood-brain barrier (BBB) may have an important role in neurodegeneration and cognitive deficits. A number of studies report that elevated blood pressure increases the permeability of BBB. In this study, we investigated the effects of antihypertensive agents, candesartan or ursodeoxycholic acid (UDCA), on BBB dysfunction and cognitive decline in wild-type mice maintained on high fat and fructose (HFF) diet for 24 weeks. In HFF-fed mice, significantly increased body weight with elevated blood pressure, plasma insulin and glucose compared with mice fed with low-fat control chow was observed. Concomitantly, significant disruption of BBB and cognitive decline were evident in the HFF-fed obese mice. Hypertension was completely prevented by the coprovision of candesartan or UDCA in mice maintained on HFF diet, while only candesartan significantly reduced the body weight compared with HFF-fed mice. Nevertheless, BBB dysfunction and cognitive decline remained unaffected by candesartan or UDCA. These data conclusively indicate that modulation of blood pressure and/or body weight may not be directly associated with BBB dysfunction and cognitive deficits in Western diet-induced obese mice, and hence antihypertensive agents may not be effective in preventing BBB disruption and cognitive decline. The findings may provide important mechanistical insights to obesity-associated cognitive decline and its therapy.
Publisher: Wiley
Date: 28-02-2017
DOI: 10.1111/JNC.13964
Abstract: Accumulation of ceramide is implicated in mediating the cellular responses to stress and aberrant sphingolipid metabolism is frequently associated with metabolic and neurodegenerative diseases. It is often assumed that (i) peripheral disturbances in sphingolipid concentrations are reflective of processes occurring in the brain, or (ii) circulating sphingolipids directly influence cerebral sphingolipid abundance. In order to address these assumptions, this study explores, in a physiological system, the metabolic pathways regulating sphingolipid metabolism in the brain and plasma of mice. Male C57Bl/6 were maintained on a low fat (control diet) or saturated fat enriched (SFA) diet with, or without the provision of sphingolipid modulating agents. Following 6 months of feeding, the abundance of seven sphingolipid classes was assessed by LC-ESI-MS/MS in the hippoc us (HPF), cerebral cortex (CTX), and plasma. Long-term consumption of the SFA diet increased ceramide and dihydroceramide in the plasma. Inhibiting de novo synthesis ameliorated this effect, while inhibition of acidic sphingomyelinase, or the sphingosine-1-phosphate receptor agonist did not. SFA feeding did not influence sphingolipid levels in either the HPF or CTX. De novo synthesis inhibition reduced ceramide in the CTX, while treatment with a sphingosine-1-phosphate receptor agonist reduced ceramides in the HPF. Analysis of the in idual ceramide species revealed the effects were chain-length dependent. Both positive and negative correlations were observed between plasma and HPF/CTX ceramide species. The findings in this study show that HPF and CTX sphingolipid concentration are influenced by distinct pathways, independent of peripheral sphingolipid concentration.
Publisher: American Society for Clinical Investigation
Date: 11-07-2019
Publisher: MyJove Corporation
Date: 21-10-2017
DOI: 10.3791/56138
Publisher: Wiley
Date: 25-01-2022
DOI: 10.1002/ALZ.12538
Abstract: The apolipoprotein E ( APOE ) genotype is the strongest genetic risk factor for late‐onset Alzheimer's disease. However, its effect on lipid metabolic pathways, and their mediating effect on disease risk, is poorly understood. We performed lipidomic analysis on three independent cohorts (the Australian Imaging, Biomarkers and Lifestyle [AIBL] flagship study, n = 1087 the Alzheimer's Disease Neuroimaging Initiative [ADNI] 1 study, n = 819 and the Busselton Health Study [BHS], n = 4384), and we defined associations between APOE ε2 and ε4 and 569 plasma/serum lipid species. Mediation analysis defined the proportion of the treatment effect of the APOE genotype mediated by plasma/serum lipid species. A total of 237 and 104 lipid species were associated with APOE ε2 and ε4, respectively. Of these 68 (ε2) and 24 (ε4) were associated with prevalent Alzheimer's disease. In idual lipid species or lipidomic models of APOE genotypes mediated up to 30% and 10% of APOE ε2 and ε4 treatment effect, respectively. Plasma lipid species mediate the treatment effect of APOE genotypes on Alzheimer's disease and as such represent a potential therapeutic target.
Publisher: Elsevier BV
Date: 09-2019
DOI: 10.1194/JLR.P094433
Publisher: MDPI AG
Date: 12-01-2023
DOI: 10.3390/S23020899
Abstract: The electroencephalogram (EEG) signal is a key parameter used to identify the different sleep stages present in an overnight sleep recording. Sleep staging is crucial in the diagnosis of several sleep disorders however, the manual annotation of the EEG signal is a costly and time-consuming process. Automatic sleep staging algorithms offer a practical and cost-effective alternative to manual sleep staging. However, due to the limited availability of EEG sleep datasets, the reliability of existing sleep staging algorithms is questionable. Furthermore, most reported experimental results have been obtained using adult EEG signals the effectiveness of these algorithms using pediatric EEGs is unknown. In this paper, we conduct an intensive study of two state-of-the-art single-channel EEG-based sleep staging algorithms, namely DeepSleepNet and AttnSleep, using a recently released large-scale sleep dataset collected from 3984 patients, most of whom are children. The paper studies how the performance of these sleep staging algorithms varies when applied on different EEG channels and across different age groups. Furthermore, all results were analyzed within in idual sleep stages to understand how each stage is affected by the choice of EEG channel and the participants’ age. The study concluded that the selection of the channel is crucial for the accuracy of the single-channel EEG-based automatic sleep staging methods. For instance, channels O1-M2 and O2-M1 performed consistently worse than other channels for both algorithms and through all age groups. The study also revealed the challenges in the automatic sleep staging of newborns and infants (1–52 weeks).
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 06-2021
DOI: 10.1161/CIRCGEN.120.003232
Abstract: The identification and understanding of therapeutic targets for atherosclerotic cardiovascular disease is of fundamental importance given its global health and economic burden. Inhibition of ANGPTL3 (angiopoietin-like 3) has demonstrated a cardioprotective effect, showing promise for atherosclerotic cardiovascular disease treatment, and is currently the focus of ongoing clinical trials. Here, we assessed the genetic basis of variation in ANGPTL3 levels in the San Antonio Family Heart Study. We assayed ANGPTL3 protein levels in ≈1000 Mexican Americans from extended pedigrees. By drawing upon existing plasma lipidome profiles and genomic data we conducted analyses to understand the genetic basis to variation in ANGPTL3 protein levels, and accordingly the correlation with the plasma lipidome. In a variance components framework, we identified that variation in ANGPTL3 was significantly heritable (h 2 =0.33, P =1.31×10 −16 ). To explore the genetic basis of this heritability, we conducted a genome-wide linkage scan and identified significant linkage (logarithm of odds =6.18) to a locus on chromosome 1 at 90 centimorgans, corresponding to the ANGPTL3 gene location. In the genomes of 23 in iduals from a single pedigree, we identified a loss-of-function variant, rs398122988 (N121Kfs*2), in ANGPTL3 , that was significantly associated with lower ANGPTL3 levels (β=−1.69 SD units, P =3.367×10 −13 ), and accounted for the linkage signal at this locus. Given the known role of ANGPTL3 as an inhibitor of endothelial and lipoprotein lipase, we explored the association of ANGPTL3 protein levels and rs398122988 with the plasma lipidome and related phenotypes, identifying novel associations with phosphatidylinositols. Variation in ANGPTL3 protein levels is heritable and under significant genetic control. Both ANGPTL3 levels and loss-of-function variants in ANGPTL3 have significant associations with the plasma lipidome. These findings further our understanding of ANGPTL3 as a therapeutic target for atherosclerotic cardiovascular disease.
Publisher: Cold Spring Harbor Laboratory
Date: 22-09-2021
DOI: 10.1101/2021.09.15.21263636
Abstract: There is mounting evidence that in utero and early life exposures may predispose an in idual to metabolic disorders in later life and dysregulation of lipid metabolism is critical in such outcomes. However, there is limited knowledge about lipid metabolism and factors causing lipid dysregulation in early life that could result in adverse health outcomes in later life. In this study, we aim to understand the lipid metabolism in pregnancy, and from birth to four years. We performed comprehensive lipid profiling of 1074 mother-child dyads in the Barwon Infant Study (BIS), a population based pre-birth cohort and measured 776 distinct lipid species across 42 lipid classes using ultra high-performance liquid chromatography (UHPLC). We measured lipids in 1032 maternal serum s les at 28 weeks’ gestation, 893 cord serum s les at birth, 793, 735, and 511 plasma s les at six, twelve months, and four years, respectively. The lipidome differed between mother and newborn and changed markedly with increasing postnatal age. Cord serum was enriched with long chain poly-unsaturated fatty acids (LC-PUFAs), and corresponding cholesteryl esters relative to the maternal serum. Alkenyl-phosphatidylethanolamine species containing LC-PUFAs increased with postnatal age, whereas the corresponding lysophospholipids and triglycerides decreased. We performed regression analyses to investigate the associations of cord serum lipid species with birth factors: gestational age, birth weight, mode of birth and duration of labor. Majority of the cord serum lipids were strongly associated with gestational age and birth weight, with most lipids showing opposing associations. Each mode of birth showed an independent association with cord serum lipids. There were marked changes in the plasma lipidome over the first four years of life. This study sheds light on lipid metabolism in infancy and early childhood and provide a framework to define the relationship between lipid metabolism and health outcomes in early childhood. This work was supported by the A*STAR-NHMRC joint call funding (1711624031).
Publisher: Springer Science and Business Media LLC
Date: 04-2023
DOI: 10.1038/S41591-023-02271-1
Abstract: Autism omics research has historically been reductionist and diagnosis centric, with little attention paid to common co-occurring conditions (for ex le, sleep and feeding disorders) and the complex interplay between molecular profiles and neurodevelopment, genetics, environmental factors and health. Here we explored the plasma lipidome (783 lipid species) in 765 children (485 diagnosed with autism spectrum disorder (ASD)) within the Australian Autism Biobank. We identified lipids associated with ASD diagnosis ( n = 8), sleep disturbances ( n = 20) and cognitive function ( n = 8) and found that long-chain polyunsaturated fatty acids may causally contribute to sleep disturbances mediated by the FADS gene cluster. We explored the interplay of environmental factors with neurodevelopment and the lipidome, finding that sleep disturbances and unhealthy diet have a convergent lipidome profile (with potential mediation by the microbiome) that is also independently associated with poorer adaptive function. In contrast, ASD lipidome differences were accounted for by dietary differences and sleep disturbances. We identified a large chr19p13.2 copy number variant genetic deletion spanning the LDLR gene and two high-confidence ASD genes ( ELAVL3 and SMARCA4 ) in one child with an ASD diagnosis and widespread low-density lipoprotein-related lipidome derangements. Lipidomics captures the complexity of neurodevelopment, as well as the biological effects of conditions that commonly affect quality of life among autistic people.
Publisher: Elsevier BV
Date: 2021
Publisher: Cold Spring Harbor Laboratory
Date: 25-08-2021
DOI: 10.1101/2021.08.20.21261814
Abstract: We integrated lipidomics and genomics to unravel the genetic architecture of lipid metabolism and identify genetic variants associated with lipid species that are putatively in the mechanistic pathway to coronary artery disease (CAD). We quantified 596 lipid species in serum from 4,492 phenotyped in iduals from the Busselton Health Study. In our discovery GWAS we identified 667 independent loci associations with these lipid species (479 novel), followed by meta-analysis and validation in two independent cohorts. Lipid endophenotypes (134) identified for CAD were associated with variation at 186 genomic loci. Associations between independent lipid-loci with coronary atherosclerosis were assessed in ∼456,000 in iduals from the UK Biobank. Of the 53 lipid-loci that showed evidence of association (P ×10 −3 ), 43 loci were associated with at least one of the 134 lipid endophenotypes. The findings of this study illustrate the value of integrative biology to investigate the genetics and lipid metabolism in the aetiology of atherosclerosis and CAD, with implications for other complex diseases.
Publisher: Springer Science and Business Media LLC
Date: 19-06-2013
Abstract: Emerging evidence suggests that disturbances in the blood–brain barrier (BBB) may be pivotal to the pathogenesis and pathology of vascular-based neurodegenerative disorders. Studies suggest that heightened systemic and central inflammations are associated with BBB dysfunction. This study investigated the effect of the anti-inflammatory nutraceuticals garlic extract-aged (GEA), alpha lipoic acid (ALA), niacin, and nicotinamide (NA) in a murine dietary-induced model of BBB dysfunction. C57BL/6 mice were fed a diet enriched in saturated fatty acids (SFA, 40% fat of total energy) for nine months to induce systemic inflammation and BBB disturbances. Nutraceutical treatment groups included the provision of either GEA, ALA, niacin or NA in the positive control SFA-group and in low-fat fed controls. Brain parenchymal extravasation of plasma derived immunoglobulin G (IgG) and large macromolecules (apolipoprotein (apo) B lipoproteins) measured by quantitative immunofluorescent microscopy, were used as markers of disturbed BBB integrity. Parenchymal glial fibrillar acidic protein (GFAP) and cyclooxygenase-2 (COX-2) were considered in the context of surrogate markers of neurovascular inflammation and oxidative stress. Total anti-oxidant status and glutathione reductase activity were determined in plasma. Brain parenchymal abundance of IgG and apoB lipoproteins was markedly exaggerated in mice maintained on the SFA diet concomitant with significantly increased GFAP and COX-2, and reduced systemic anti-oxidative status. The nutraceutical GEA, ALA, niacin, and NA completely prevented the SFA-induced disturbances of BBB and normalized the measures of neurovascular inflammation and oxidative stress. The anti-inflammatory nutraceutical agents GEA, ALA, niacin, or NA are potent inhibitors of dietary fat-induced disturbances of BBB induced by systemic inflammations.
Publisher: Frontiers Media SA
Date: 06-06-2022
Abstract: Cardiovascular disease (CVD) is the leading cause of mortality worldwide and is the leading cause of death in the US. Lipid dysregulation is a well-known precursor to metabolic diseases, including CVD. There is a growing body of literature that suggests MRI-derived epicardial fat volume, or epicardial adipose tissue (EAT) volume, is linked to the development of coronary artery disease. Interestingly, epicardial fat is also actively involved in lipid and energy homeostasis, with epicardial adipose tissue having a greater capacity for release and uptake of free fatty acids. However, there is a scarcity of knowledge on the influence of plasma lipids on EAT volume. The focus of this study is on the identification of novel lipidomic species associated with CMRI-derived measures of epicardial fat in Mexican American in iduals. We performed lipidomic profiling on 200 Mexican American in iduals. High-throughput mass spectrometry enabled rapid capture of precise lipidomic profiles, providing measures of 799 unique species from circulating plasma s les. Because of our extended pedigree design, we utilized a standard quantitative genetic linear mixed model analysis to determine whether lipids were correlated with EAT by formally testing for association between each lipid species and the CMRI epicardial fat phenotype. After correction for multiple testing using the FDR approach, we identified 135 lipid species showing significant association with epicardial fat. Of those, 131 lipid species were positively correlated with EAT, where increased circulating lipid levels were correlated with increased epicardial fat. Interestingly, the top 10 lipid species associated with an increased epicardial fat volume were from the deoxyceramide (Cer(m)) and triacylglycerol (TG) families. Deoxyceramides are atypical and neurotoxic sphingolipids. Triacylglycerols are an abundant lipid class and comprise the bulk of storage fat in tissues. Pathologically elevated TG and Cer(m) levels are related to CVD risk and, in our study, to EAT volume. Our results indicate that specific lipid abnormalities such as enriched saturated triacylglycerols and the presence of toxic ceramides Cer(m) in plasma of our in iduals could precede CVD with increased EAT volume.
Publisher: Elsevier BV
Date: 09-2020
Publisher: Elsevier BV
Date: 09-2019
Publisher: American Chemical Society (ACS)
Date: 03-2019
DOI: 10.1021/ACSCHEMNEURO.9B00039
Abstract: Non-insulin-dependent diabetes mellitus (NIDDM) is reported to increase the risk of cognitive impairment and dementia. However, the underlying mechanisms are not fully understood. While the brain homeostasis of metals and lipids is pivotal to maintaining energy metabolism and redox homeostasis for healthy brain function, no studies have reported hippoc al metal and biochemical changes in NIDDM. Therefore, we here utilized direct spectroscopic imaging to reveal the elemental distribution within the hippoc al subregions of an established murine model of NIDDM, db/db mice. In 26-week-old insulin resistant db/db mice, X-ray fluorescence microscopy revealed that the Cu content within the dentate gyrus and CA3 was significantly greater than that of the age-matched nondiabetic control mice. In addition, Fourier transform infrared (FTIR) spectroscopy analysis indicated a significant increase in the abundance of lactate within the corpus callosum (CC), dentate gyrus, CA1, and CA3 regions of diabetic db/db mice compared to that of the control, indicating altered energy metabolism. FTIR analysis also showed a significant decrease in the level of lipid methylene and ester within the CC of db/db mice. Furthermore, immunomicroscopy analyses demonstrated the increase in the level of glial fibrillary acidic protein expression and peri-vascular extravasation of IgG, indicating astrogliosis and blood-brain barrier dysfunction, respectively. These data suggest that astrogliosis-induced alterations in the supply of Cu, lipids, and energy substrates may be involved in the mechanisms of NIDDM-associated cognitive decline.
Publisher: Elsevier BV
Date: 04-2020
Publisher: Frontiers Media SA
Date: 12-2017
Publisher: Springer Science and Business Media LLC
Date: 21-03-2021
Publisher: American Diabetes Association
Date: 28-10-2020
DOI: 10.2337/DB20-0653
Abstract: The incidence of atrial fibrillation (AF) is higher in patients with diabetes. The goal of this study was to assess if the addition of plasma lipids to traditional risk factors could improve the ability to detect and predict future AF in patients with type 2 diabetes. Logistic regression models were used to identify lipids associated with AF or future AF from plasma lipids (n = 316) measured from participants in the ADVANCE trial (n = 3,772). To gain mechanistic insight, follow-up lipid analysis was undertaken in a mouse model that has an insulin-resistant heart and is susceptible to AF. Sphingolipids, cholesteryl esters, and phospholipids were associated with AF prevalence, whereas two monosialodihexosylganglioside (GM3) ganglioside species were associated with future AF. For AF detection and prediction, addition of six and three lipids, respectively, to a base model (n = 12 conventional risk factors) increased the C-statistics (detection: from 0.661 to 0.725 prediction: from 0.674 to 0.715) and categorical net reclassification indices. The GM3(d18:1/24:1) level was lower in patients in whom AF developed, improved the C-statistic for the prediction of future AF, and was lower in the plasma of the mouse model susceptible to AF. This study demonstrates that plasma lipids have the potential to improve the detection and prediction of AF in patients with diabetes.
Publisher: Public Library of Science (PLoS)
Date: 09-12-2020
Publisher: Public Library of Science (PLoS)
Date: 28-09-2020
Publisher: Public Library of Science (PLoS)
Date: 13-04-2015
Start Date: 2023
End Date: 12-2025
Amount: $569,146.00
Funder: Australian Research Council
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