lipid species
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2022 ◽  
Vol 12 ◽  
Author(s):  
Sofie Olund Villumsen ◽  
Rui Benfeitas ◽  
Andreas Dehlbæk Knudsen ◽  
Marco Gelpi ◽  
Julie Høgh ◽  
...  

People living with HIV (PLWH) require life-long anti-retroviral treatment and often present with comorbidities such as metabolic syndrome (MetS). Systematic lipidomic characterization and its association with the metabolism are currently missing. We included 100 PLWH with MetS and 100 without MetS from the Copenhagen Comorbidity in HIV Infection (COCOMO) cohort to examine whether and how lipidome profiles are associated with MetS in PLWH. We combined several standard biostatistical, machine learning, and network analysis techniques to investigate the lipidome systematically and comprehensively and its association with clinical parameters. Additionally, we generated weighted lipid-metabolite networks to understand the relationship between lipidomic profiles with those metabolites associated with MetS in PLWH. The lipidomic dataset consisted of 917 lipid species including 602 glycerolipids, 228 glycerophospholipids, 61 sphingolipids, and 26 steroids. With a consensus approach using four different statistical and machine learning methods, we observed 13 differentially abundant lipids between PLWH without MetS and PLWH with MetS, which mainly belongs to diacylglyceride (DAG, n = 2) and triacylglyceride (TAG, n = 11). The comprehensive network integration of the lipidomics and metabolomics data suggested interactions between specific glycerolipids’ structural composition patterns and key metabolites involved in glutamate metabolism. Further integration of the clinical data with metabolomics and lipidomics resulted in the association of visceral adipose tissue (VAT) and exposure to earlier generations of antiretroviral therapy (ART). Our integrative omics data indicated disruption of glutamate and fatty acid metabolism, suggesting their involvement in the pathogenesis of PLWH with MetS. Alterations in the lipid homeostasis and glutaminolysis need clinical interventions to prevent accelerated aging in PLWH with MetS.


2022 ◽  
Vol 13 (1) ◽  
Author(s):  
Denise Wolrab ◽  
Robert Jirásko ◽  
Eva Cífková ◽  
Marcus Höring ◽  
Ding Mei ◽  
...  

AbstractPancreatic cancer has the worst prognosis among all cancers. Cancer screening of body fluids may improve the survival time prognosis of patients, who are often diagnosed too late at an incurable stage. Several studies report the dysregulation of lipid metabolism in tumor cells, suggesting that changes in the blood lipidome may accompany tumor growth. Here we show that the comprehensive mass spectrometric determination of a wide range of serum lipids reveals statistically significant differences between pancreatic cancer patients and healthy controls, as visualized by multivariate data analysis. Three phases of biomarker discovery research (discovery, qualification, and verification) are applied for 830 samples in total, which shows the dysregulation of some very long chain sphingomyelins, ceramides, and (lyso)phosphatidylcholines. The sensitivity and specificity to diagnose pancreatic cancer are over 90%, which outperforms CA 19-9, especially at an early stage, and is comparable to established diagnostic imaging methods. Furthermore, selected lipid species indicate a potential as prognostic biomarkers.


2022 ◽  
pp. 1-21
Author(s):  
Mamta Rai ◽  
Fabio Demontis

Skeletal muscle health and function are important determinants of systemic metabolic homeostasis and organism-wide responses, including disease outcome. While it is well known that exercise protects the central nervous system (CNS) from aging and disease, only recently this has been found to depend on the endocrine capacity of skeletal muscle. Here, we review muscle-secreted growth factors and cytokines (myokines), metabolites (myometabolites), and other unconventional signals (e.g. bioactive lipid species, enzymes, and exosomes) that mediate muscle-brain and muscle-retina communication and neuroprotection in response to exercise and associated processes, such as the muscle unfolded protein response and metabolic stress. In addition to impacting proteostasis, neurogenesis, and cognitive functions, muscle-brain signaling influences complex brain-dependent behaviors, such as depression, sleeping patterns, and biosynthesis of neurotransmitters. Moreover, myokine signaling adapts feeding behavior to meet the energy demands of skeletal muscle. Contrary to protective myokines induced by exercise and associated signaling pathways, inactivity and muscle wasting may derange myokine expression and secretion and in turn compromise CNS function. We propose that tailoring muscle-to-CNS signaling by modulating myokines and myometabolites may combat age-related neurodegeneration and brain diseases that are influenced by systemic signals.


Author(s):  
Aya Mousa ◽  
Kevin Huynh ◽  
Stacey J Ellery ◽  
Boyd J Strauss ◽  
Anju E Joham ◽  
...  

Abstract Background Dyslipidaemia is a feature of polycystic ovary syndrome (PCOS) and may augment metabolic dysfunction in this population. Objective Using comprehensive lipidomic profiling and gold-standard metabolic measures, we examined whether distinct lipid biomarkers were associated with metabolic risk in women with and without PCOS. Methods Using pre-existing data and bio-banked samples from 76 women (n=42 with PCOS), we profiled >700 lipid species by mass spectrometry. Lipids were compared between women with and without PCOS and correlated with direct measures of adiposity (dual X-ray absorptiometry and computed tomography) and insulin sensitivity (hyperinsulinaemic-euglycaemic clamp), as well as fasting insulin, HbA1c, and hormonal parameters (luteinizing and follicle stimulating hormones; total and free testosterone; sex hormone-binding globulin [SHBG]; and free androgen index [FAI]). Multivariable linear regression was used with correction for multiple testing. Results Despite finding no differences by PCOS status, lysophosphatidylinositol (LPI) species esterified with an 18:0 fatty acid were the strongest lipid species associated with all the metabolic risk factors measured in women with and without PCOS. Across the cohort, higher concentrations of LPI(18:0) and lower concentrations of lipids containing docosahexaenoic acid (DHA, 22:6) n-3 polyunsaturated fatty acids (PUFA) were associated with higher adiposity, insulin resistance, fasting insulin, HbA1c and FAI, and lower SHBG. Conclusions Our data indicate that a distinct lipidomic signature comprising high LPI(18:0) and low DHA-containing lipids are associated with key metabolic risk factors that cluster in PCOS, independent of PCOS status. Prospective studies are needed to corroborate these findings in larger cohorts of women with varying PCOS phenotypes.


Nutrients ◽  
2021 ◽  
Vol 14 (1) ◽  
pp. 158
Author(s):  
Talat Bashir Ahmed ◽  
Merete Eggesbø ◽  
Rachel Criswell ◽  
Olaf Uhl ◽  
Hans Demmelmair ◽  
...  

Human milk lipids are essential for infant health. However, little is known about the relationship between total milk fatty acid (FA) composition and polar lipid species composition. Therefore, we aimed to characterize the relationship between the FA and polar lipid species composition in human milk, with a focus on differences between milk with higher or lower milk fat content. From the Norwegian Human Milk Study (HUMIS, 2002–2009), a subset of 664 milk samples were analyzed for FA and polar lipid composition. Milk samples did not differ in major FA, phosphatidylcholine, or sphingomyelin species percentages between the highest and lowest quartiles of total FA concentration. However, milk in the highest FA quartile had a lower phospholipid-to-total-FA ratio and a lower sphingomyelin-to-phosphatidylcholine ratio than the lowest quartile. The only FAs associated with total phosphatidylcholine or sphingomyelin were behenic and tridecanoic acids, respectively. Milk FA and phosphatidylcholine and sphingomyelin species containing these FAs showed modest correlations. Associations of arachidonic and docosahexaenoic acids with percentages of phosphatidylcholine species carrying these FAs support the conclusion that the availability of these FAs limits the synthesis of phospholipid species containing them.


Biomolecules ◽  
2021 ◽  
Vol 12 (1) ◽  
pp. 40
Author(s):  
Arati Tripathi ◽  
Saranna Fanning ◽  
Ulf Dettmer

Neuronal loss in Parkinson’s disease and related brain diseases has been firmly linked to the abundant neuronal protein α-synuclein (αS). However, we have gained surprisingly little insight into how exactly αS exerts toxicity in these diseases. Hypotheses of proteotoxicity, disturbed vesicle trafficking, mitochondrial dysfunction and other toxicity mechanisms have been proposed, and it seems possible that a combination of different mechanisms may drive pathology. A toxicity mechanism that has caught increased attention in the recent years is αS-related lipotoxicity. Lipotoxicity typically occurs in a cell when fatty acids exceed the metabolic needs, triggering a flux into harmful pathways of non-oxidative metabolism. Genetic and experimental approaches have revealed a significant overlap between lipid storage disorders, most notably Gaucher’s disease, and synucleinopathies. There is accumulating evidence for lipid aberrations causing synuclein misfolding as well as for αS excess and misfolding causing lipid aberration. Does that mean the key problem in synucleinopathies is lipotoxicity, the accumulation of harmful lipid species or alteration in lipid equilibrium? Here, we review the existing literature in an attempt to get closer to an answer.


Viruses ◽  
2021 ◽  
Vol 14 (1) ◽  
pp. 3
Author(s):  
Katherine E. Havranek ◽  
Judith Mary Reyes Ballista ◽  
Kelly Marie Hines ◽  
Melinda Ann Brindley

The viral lifecycle is critically dependent upon host lipids. Enveloped viral entry requires fusion between viral and cellular membranes. Once an infection has occurred, viruses may rely on host lipids for replication and egress. Upon exit, enveloped viruses derive their lipid bilayer from host membranes during the budding process. Furthermore, host lipid metabolism and signaling are often hijacked to facilitate viral replication. We employed an untargeted HILIC-IM-MS lipidomics approach and identified host lipid species that were significantly altered during vesicular stomatitis virus (VSV) infection. Many glycerophospholipid and sphingolipid species were modified, and ontological enrichment analysis suggested that the alterations to the lipid profile change host membrane properties. Lysophosphatidylcholine (LPC), which can contribute to membrane curvature and serve as a signaling molecule, was depleted during infection, while several ceramide sphingolipids were augmented during infection. Ceramide and sphingomyelin lipids were also enriched in viral particles, indicating that sphingolipid metabolism is important during VSV infection.


2021 ◽  
Author(s):  
Julia Hernández Lluesa ◽  
Luis Carlos López-Romero ◽  
José Jesús Broseta ◽  
Marta Roca Marugán ◽  
Iris Viejo Boyano ◽  
...  

Abstract Background. Lipids are molecules that constitute a fundamental part of the plasma. Chronic kidney disease (CKD) produces profound changes in lipid metabolism, and associated lipid disorders, in turn, contribute to the progression of CKD. Patients on peritoneal dialysis (PD) have more atherogenic lipid profiles than non-dialysis-dependent CKD patients. Methods. Single-center prospective observational study of a cohort of CKD patients who started renal replacement therapy with continuous ambulatory peritoneal dialysis. The differences in the lipid profile and analytical variables before and six months after the start of peritoneal dialysis were analyzed. Samples were analyzed on an Ultra-Performance Liquid Chromatography system. Results. Thirty-nine patients were enrolled in this study. Their mean age was 57.9 ± 16.3 years. A total of 157 endogenous lipid species of 11 lipid subclasses were identified. There were significant increases in total free fatty acids (p< 0.05), diacylglycerides (p <0.01), triacylglycerides, (p <0.01), phosphatidylcholines (p <0.01), phosphatidylethanolamines (p <0.01), ceramides (p <0.01), sphingomyelins (p <0.01), and cholesterol esters (p<0.01) from baseline to 6 months. However, there were no differences in the classical lipid markers, neither lysophosphatidylcholines, monoacylglycerides, and sphingosine levels. Conclusions. Patients on PD present changes in the lipidomic profile beyond the classic markers of dyslipidemia, that suggest an increased cardiovascular risk in them.


2021 ◽  
Author(s):  
Anne Baumann ◽  
Andrew R Denninger ◽  
Marek Domin ◽  
Bruno Deme ◽  
Daniel A Kirschner

Myelin is a natural and dynamic multilamellar membrane structure that continues to be of significant biological and neurological interest, especially its biosynthesis and assembly in the context of its normal formation and renewal, and pathological breakdown. To explore further the usefulness of neutron diffraction in the structural analysis of myelin, we investigated the use of in vivo labeling by metabolically incorporating via drinking water nontoxic levels of deuterium (2H; D) into pregnant dams and their developing embryos. All of the mice were sacrificed when the pups were about 60 days old. Myelinated nerves were dissected, fixed in glutaraldehyde and examined by neutron diffraction. Parallel samples that were unfixed were frozen for mass spectrometry (MS). Analysis of the neutron diffraction patterns of the sciatic nerves from deuterium-fed mice (D mice) versus the controls (H mice) showed no appreciable differences in myelin periodicity, but major differences in the intensities of the Bragg peaks. The neutron scattering density profiles showed an appreciable increase in density at the center of the membrane bilayer in the D mice, particularly in the pups. MS analysis of the lipids isolated from the trigeminal nerves demonstrated that the level of D was greater in the pups compared to their mother: 97.6% +/- 2.0% (n=54; range 89.6% to 99.6%) versus 60.6% +/- 26.4% (n=27; range 11.4% to 97.3%). Deuteration in the mother also varied by lipid species, and among lipid subspecies. Three molecular species of phosphatidylcholine (PC), phosphatidylinositol (PI), and diglycerol (DG) were the most deuterated lipids, and sulfatide (SHexCer), one species of sphingomyelin (SM), and triacylglycerol (TG) were the least deuterated. The distribution pattern of deuterium in the D pups was always bell-shaped, and the average number of D atoms ranged from a low of ~4 in fatty acid (FA), to a high of ~9 in cerebroside (HexCer). By contrast, in D dam only about one third of the lipids had symmetric bell-shaped distributions; most had more complex, overlapping distributions that were weighted toward a lower average number of D atom labels. The average number of D atoms ranged from a low of ~3 to 4 in FA and in one species of SHexCer, to a high of 6 to 7 in HexCer and SM. In D pups, the consistently high level of deuteration can be attributed to their de novo lipogenesis during gestation and continuation of rapid myelination postnatally. In D dam, the widely varying levels of deuteration of lipids likely depends on the relative metabolic stability of the particular lipid species during myelin maintenance in the mature animal. Our current findings demonstrate that stably-incorporated D label can be detected and localized using neutron diffraction in a complex tissue such as myelin; and moreover, that MS can be used to screen a broad range of deuterated lipid species to monitor differential rates of lipid turnover. In addition to helping to develop a comprehensive understanding of the de novo synthesis and turnover of specific lipids in normal and abnormal myelin, our results also suggest application to myelin proteins, as well as more broadly to the molecular constituents of other biological tissues.


2021 ◽  
Author(s):  
Helena Castane ◽  
Simona Iftimie ◽  
Gerard Baiges-Gaya ◽  
Elisabet Rodriguez-Tomas ◽  
Andrea Jimenez-Franco ◽  
...  

Background: Lipids are involved in the interaction between viral infection and the host metabolic and immunological response. Several studies comparing the lipidome of COVID-19-positive hospitalized patients vs. healthy subjects have already been reported. It is largely unknown, however, whether these differences are specific to this disease. The present study compared the lipidomic signature of hospitalized COVID-19-positive patients with that of healthy subjects, and with COVID-19-negative patients hospitalized for other infectious/inflammatory diseases. Potential COVID-19 biomarkers were identified. Methods: We analyzed the lipidomic signature of 126 COVID-19-positive patients, 45 COVID-19-negative patients hospitalized with other infectious/inflammatory diseases and 50 healthy volunteers. Results were interpreted by machine learning. Results: We identified acylcarnitines, lysophosphatidylethanolamines, arachidonic acid and oxylipins as the most altered species in COVID-19-positive patients compared to healthy volunteers. However, we found similar alterations in COVID-19-negative patients. By contrast, we identified lysophosphatidylcholine 22:6-sn2, phosphatidylcholine 36:1 and secondary bile acids as the parameters that had the greatest capacity to discriminate between COVID-19-positive and COVID-19-negative patients. Conclusion: This study shows that COVID-19 infection shares many lipid alterations with other infectious/inflammatory diseases, but differentiating them from the healthy population. Also, we identified some lipid species the alterations of which distinguish COVID-19-positive from Covid-19-negative patients. Our results highlight the value of integrating lipidomics with machine learning algorithms to explore the pathophysiology of COVID-19 and, consequently, improve clinical decision making.


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