Project description:Use untargeted lipidomics to investigate differences in hepatic lipid profile between wild type and knockout mice. Mice were fed with high fat diet for 10 weeks and sacrificed under randomly fed condition. Liver were harvested freshly and frozen into liquid nitrogen immediately. Each sample was combined liver tissues from three individual mice in the same group.
Project description:Plasma high-density lipoprotein (HDL), originally studied for its role in lipid transport, is now appreciated to have wide-ranging biological functions that become defective during disease. While >200 lipids have collectively been detected in HDL, published HDL lipidomic analyses in different diseases have commonly been targeted to prespecified subsets of lipids. Here, we report the results of untargeted lipidomic analysis of HDL isolated from 101 subjects referred for computed tomographic coronary imaging for whom multiple additional clinical and lipoprotein metadata were measured. Unsupervised clustering of the total HDL lipidome revealed that the subjects fell into one of two discrete groups, herein referred to as HDL "metabotypes." Patients in metabotype 1 were likelier to be female and tended to have a less atherogenic lipoprotein profile, higher HDL cholesterol efflux capacity (CEC), and lower-grade non-calcified burden on coronary imaging than metabotype 2 counterparts. Specific lipids were relatively enriched in metabotype 1 HDL. Linear modeling revealed that several of these lipids were positively associated with CEC, statin use, HDL size, and HDL particle number, and positively correlated with HDL apolipoprotein A-1, suggesting that they may be informative HDL biomarkers. Taken together, we posit a novel, clinically relevant categorization for HDL revealed by systems biology.
Project description:Understanding the biological mechanisms underlying racial differences in diseases is crucial to developing targeted prevention and treatment. There is, however, limited knowledge of the impact of race on lipids. To address this, we performed comprehensive lipidomics analyses to evaluate racial differences in lipid species among 506 non-Hispanic White (NHW) and 163 non-Hispanic Black (NHB) women. Plasma lipidomic profiling quantified 982 lipid species. We used multivariable linear regression models, adjusted for confounders, to identify racial differences in lipid species and corrected for multiple testing using a Bonferroni-adjusted p-value < 10-5. We identified 248 lipid species that were significantly associated with race. NHB women had lower levels of several lipid species, most notably in the triacylglycerols sub-pathway (N = 198 out of 518) with 46 lipid species exhibiting an absolute percentage difference ≥ 50% lower in NHB compared with NHW women. We report several novel differences in lipid species between NHW and NHB women, which may underlie racial differences in health and have implications for disease prevention.
Project description:Sarcopenia, a multifactorial systemic disorder, has attracted extensive attention, yet its pathogenesis is not fully understood, partly due to limited research on the relationship between lipid metabolism abnormalities and sarcopenia. Lipidomics offers the possibility to explore this relationship. Our research utilized LC/MS-based nontargeted lipidomics to investigate the lipid profile changes as-sociated with sarcopenia, aiming to enhance understanding of its underlying mechanisms. The study included 40 sarcopenia patients and 40 control subjects matched 1:1 by sex and age. Plasma lipids were detected and quantified, with differential lipids identified through univariate and mul-tivariate statistical analyses. A weighted correlation network analysis (WGCNA) and MetaboAna-lyst were used to identify lipid modules related to the clinical traits of sarcopenia patients and to conduct pathway analysis, respectively. A total of 34 lipid subclasses and 1446 lipid molecules were detected. Orthogonal partial least squares discriminant analysis (OPLS-DA) identified 80 differen-tial lipid molecules, including 38 phospholipids. Network analysis revealed that the brown module (encompassing phosphatidylglycerol (PG) lipids) and the yellow module (containing phosphati-dylcholine (PC), phosphatidylserine (PS), and sphingomyelin (SM) lipids) were closely associated with the clinical traits such as maximum grip strength and skeletal muscle mass (SMI). Pathway analysis highlighted the potential role of the glycerophospholipid metabolic pathway in lipid me-tabolism within the context of sarcopenia. These findings suggest a correlation between sarcopenia and lipid metabolism disturbances, providing valuable insights into the disease's underlying mechanisms and indicating potential avenues for further investigation.
Project description:BackgroundNonpuerperal mastitis (NPM) is a disease that presents with redness, swelling, heat, and pain during nonlactation and can often be confused with breast cancer. The etiology of NPM remains elusive; however, emerging clinical evidence suggests a potential involvement of lipid metabolism.MethodLiquid chromatography‒mass spectrometry (LC/MS)-based untargeted lipidomics analysis combined with multivariate statistics was performed to investigate the NPM lipid change in breast tissue. Twenty patients with NPM and 10 controls were enrolled in this study.ResultsThe results revealed significant differences in lipidomics profiles, and a total of 16 subclasses with 14,012 different lipids were identified in positive and negative ion modes. Among these lipids, triglycerides (TGs), phosphatidylethanolamines (PEs) and cardiolipins (CLs) were the top three lipid components between the NPM and control groups. Subsequently, a total of 35 lipids were subjected to screening as potential biomarkers, and the chosen lipid biomarkers exhibited enhanced discriminatory capability between the two groups. Furthermore, pathway analysis elucidated that the aforementioned alterations in lipids were primarily associated with the arachidonic acid metabolic pathway. The correlation between distinct lipid populations and clinical phenotypes was assessed through weighted gene coexpression network analysis (WGCNA).ConclusionsThis study demonstrates that untargeted lipidomics assays conducted on breast tissue samples from patients with NPM exhibit noteworthy alterations in lipidomes. The findings of this study highlight the substantial involvement of arachidonic acid metabolism in lipid metabolism within the context of NPM. Consequently, this study offers valuable insights that can contribute to a more comprehensive comprehension of NPM in subsequent investigations.Trial registrationShuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine (Number: 2019-702-57; Date: July 2019).
Project description:Background and Aims: The diagnosis of Wilson's disease (WD) is challenging by clinical or genetic criteria. A typical early pathological change of WD is the increased liver lipid deposition and lowered serum triglyceride (TG). Therefore, the contents of serum lipids may provide evidence for screening of biomarkers for WD. Methods: 34 WD patients, 31 WD relatives, and 65 normal controls were enrolled in this study. Serum lipidomics data was acquired by an ultra-high-performance liquid chromatography high-resolution mass spectrometry system, and the data were analyzed by multivariate statistical methods. Results: Of all 510 identified lipids, there are 297 differential lipids between the WD and controls, 378 differential lipids between the relatives and controls, and 119 differential lipids between the patients and relatives. In WD, the abundances of most saturated TG were increased, whereas other unsaturated lipids decreased, including phosphatidylcholine (PC), sphingomyelin (SM), lysophosphatidylcholine (LPC), ceramide (Cer), and phosphatidylserine (PS). We also found many serum lipid species may be used as biomarkers for WD. The areas under the receiver operating characteristic curve (AUC) of PS (35:0), PS (38:5), and PS (34:0) were 0.919, 0.843, and 0.907. The AUCs of TG (38:0) and CerG1 (d42:2) were 0.948 and 0.915 and the AUCs of LPC (17:0) and LPC (15:0) were 0.980 and 0.960, respectively. The lipid biomarker panel exhibits good diagnostic performance for WD. The correlation networks were built among the different groups and the potential mechanisms of differential lipids were discussed. Interestingly, similar lipid profile of WD is also found in their relatives, which indicated the changes may also related to the mutation of the ATP7B gene. Conclusions: Lipid deregulation is another important hallmark of WD besides the deposition of copper. Our lipidomic results provide new insights into the diagnostic and therapeutic targets of WD.
Project description:Seaweeds are macrophytic algae that have been gaining interest as alternative healthy foods, renewable drug sources, and climate change mitigation agents. In terms of their nutritional value, seaweeds are renowned for their high content of biologically active polyunsaturated fatty acids. However, little is known about the regiochemistry-the geometry and position of carbon-carbon double bonds-of free and conjugated fatty acids in seaweeds. In the present work, a detailed characterization of the seaweed lipidome was achieved based on untargeted HRMS-based analysis and lipid derivatization with a photochemical aza-Paternò-Büchi reaction. A triple-data processing strategy was carried out to achieve high structural detail on the seaweed lipidome, i.e., (i) a first data processing workflow with all samples for aligning peak and statistical analysis that led to the definition of lipid sum compositions (e.g., phosphatidylglycerol (PG) 34:1), (ii) a second data processing workflow in which the samples of each seaweed were processed separately to annotate molecular lipids with known fatty acyl isomerism (e.g., PG 16:0_18:1), and (iii) the annotation of lipid regioisomers following MS/MS annotation of the lipid derivatives obtained following the aza-Paternò-Büchi reaction (e.g., PG 16:0_18:1 ω-9). Once the platform was set up, the lipid extracts from 8 seaweed species from different seaweed families were characterized, describing over 900 different lipid species, and information on the regiochemistry of carbon-carbon double bonds uncovered unknown peculiarities of seaweeds belonging to different families. The overall analytical approach helped to fill a gap in the knowledge of the nutritional composition of seaweeds.
Project description:Extracellular vesicles (EV) are membranous vesicles considered as significant players in cell-to-cell communication. Milk provides adequate nutrition, transfers immunity, and promotes neonatal development, and milk EV are suggested to play a crucial role in these processes. Milk samples were obtained on days 0, 7, and 14 after parturition from sows receiving either a standard diet (ω-6:ω-3 = 13:1) or a test diet enriched in ω-3 (ω-6:ω-3 = 4:1). EV were isolated using ultracentrifugation coupled with size exclusion chromatography, and characterized by nanoparticle tracking analysis, transmission electron microscopy, and assessment of EV markers via Western blotting. The lipidome was determined following a liquid chromatography-quadrupole time-of-flight mass spectrometry approach. Here, we show that different stages of lactation (colostrum vs mature milk) have a distinct extracellular vesicle lipidomic profile. The distinct lipid content can be further explored to understand and regulate milk EV functionalities and primordial for enabling their diagnostic and therapeutic potential.