Melbourne Medical School Collected Works - Research Publications
Permanent URI for this collection
Search Results
1 - 6 of 6
-
ItemOntogeny of circulating lipid metabolism in pregnancy and early childhood - a longitudinal population study(eLIFE SCIENCES PUBL LTD, 2022-03-02)BACKGROUND: There is mounting evidence that in utero and early life exposures may predispose an individual 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. METHODS: 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 samples at 28 weeks' gestation, 893 cord serum samples at birth, 793, 735, and 511 plasma samples 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. RESULTS: 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. CONCLUSIONS: 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. FUNDING: This work was supported by the A*STAR-NHMRC joint call funding (1711624031).
-
ItemLipidomic Signatures of Changes in Adiposity: A Large Prospective Study of 5849 Adults from the Australian Diabetes, Obesity and Lifestyle Study(MDPI, 2021-09)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 samples. 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 individuals 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 individuals at risk of weight gain or WC increase and provide important insight into the biological role of lipids in obesity.
-
ItemOral Supplementation of an Alkylglycerol Mix Comprising Different Alkyl Chains Effectively Modulates Multiple Endogenous Plasmalogen Species in Mice(MDPI, 2021-05)Plasmalogens or alkenylphospholipids are a sub-class of glycerophospholipids with numerous biological functions and are thought to have protective effects against metabolic disease. Dietary supplementation with alkylglycerols (AKGs) has been shown to increase endogenous plasmalogen levels, however effective modulation of different molecular plasmalogen species has not yet been demonstrated. In this study, the effects of an orally-administered AKG mix (a mixture of chimyl, batyl and selachyl alcohol at a 1:1:1 ratio) on plasma and tissue lipids, including plasmalogens, was evaluated. Mice on a Western-type diet were treated with either an AKG mix or vehicle (lecithin) for 1, 2, 4, 8 and 12 weeks. Treatment with the AKG mix significantly increased the total plasmalogen content of plasma, liver and adipose tissue as a result of elevations in multiple plasmalogen species with different alkenyl chains. Alkylphospholipids, the endogenous precursors of plasmalogens, showed a rapid and significant increase in plasma, adipose tissue, liver and skeletal muscle. A significant accumulation of alkyl-diacylglycerol and lyso-ether phospholipids was also observed in plasma and tissues. Additionally, the dynamics of plasmalogen-level changes following AKG mix supplementation differed between tissues. These findings indicate that oral supplementation with an AKG mix is capable of upregulating and maintaining stable expression of multiple molecular plasmalogen species in circulation and tissues.
-
ItemNovel Lipid Species for Detecting and Predicting Atrial Fibrillation in Patients With Type 2 Diabetes(AMER DIABETES ASSOC, 2021-01)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.
-
ItemConcordant peripheral lipidome signatures in two large clinical studies of Alzheimer's disease(NATURE PORTFOLIO, 2020-11-10)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 samples 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 GM3 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.
-
ItemKrill Oil Has Different Effects on the Plasma Lipidome Compared with Fish Oil Following 30 Days of Supplementation in Healthy Women: A Randomized Controlled and Crossover Study(MDPI, 2020-09)This is a follow-up of our previous postprandial study and it focused on the plasma lipidomic responses to 30 days of krill oil (KO) versus fish oil (FO) supplementations in healthy women. Eleven women (aged 18-50 years) consumed KO or FO for 30 days in a randomized, cross-over study, with at least a four-week washout period between supplementations. The daily supplements provided 1.27 g/day of long-chain (LC) omega-3 polyunsaturated fatty acids (PUFA) from KO (containing 0.76 g eicosapentaenoic acid (EPA), 0.42 g docosahexaenoic acid (DHA)) and 1.44 g/day from FO (containing 0.79 g EPA, 0.47 g DHA). Fasting plasma samples at days 0, 15, and 30 were analyzed using gas chromatography and liquid chromatography electrospray ionisation-tandem mass spectrometry. KO resulted in a significantly greater relative area under the curve (relAUC) for plasma EPA after 30 days. Lipidomic analysis showed that 26 of 43 lipid molecular species had a significantly greater relAUC in the KO group, while 17/43 showed a significantly lower relAUC compared with the FO group. More than 38% of the lipids species which increased more following KO contained omega-3 PUFA, while where FO was greater than KO, only 12% contained omega-3 PUFA. These data show that KO and FO do not have equivalent effects on the plasma lipidome.