-
Redox Biology Dec 2022There is no gold standard for evaluating the severity of community-acquired pneumonia (CAP), and it is still based on a score. This study aimed to use the metabolomics...
There is no gold standard for evaluating the severity of community-acquired pneumonia (CAP), and it is still based on a score. This study aimed to use the metabolomics method to find promised biomarkers in assessing disease severity and potential therapeutic targets for CAP. The result found that the metabolites in the plasma samples of CAP patients had significantly different between the acute phase and the remission phase, especially lysophosphatidylcholine (LPCs) in glycerophospholipids, whose levels are negatively linked to the severity of the disease. Subsequently, the two key metabolites of myristoyl lysophosphatidylcholine (LPC 14:0) and LPC 16:1 were screened. We analyzed the predictive performance of the two metabolites using Spearman-related analysis and ROC curves, and LPC14:0 showed more satisfactory diagnostic performance than LPC16:1. Then we explored the protective role and mechanism of LPC 14:0 in animal and cell models. The results showed that LPC 14:0 could inhibit the LPS-induced secretion of IL-1β, IL-6, and TNF-α, lower the ROS and MDA levels, and decreased the depletion of SOD and GSH, thereby reducing lung tissue and cell damage, such as down-regulating the protein level in BALF, lung W/D ratio, MPO activity, and apoptosis. We found that LPC 14:0 inhibited LPS-induced inflammatory response and oxidative stress, and the above protection was achieved by inhibiting LPS-induced activation of the NLRP3 inflammasome. LPC 14:0 may serve as a novel biomarker for predicting the severity of CAP. In addition, our exploration of the role of LPC 14:0 in animal and cellular models has reinforced its promise as a therapeutic target to improve the clinical efficacy for CAP.
Topics: Animals; Lysophosphatidylcholines; Lipopolysaccharides; Pneumonia; Inflammasomes; Biomarkers; NLR Family, Pyrin Domain-Containing 3 Protein
PubMed: 36459717
DOI: 10.1016/j.redox.2022.102556 -
International Journal of Molecular... Jul 2022The bioactive lipid lysophosphatidylcholine (LPC), a major phospholipid component of oxidized low-density lipoprotein (Ox-LDL), originates from the cleavage of... (Review)
Review
The bioactive lipid lysophosphatidylcholine (LPC), a major phospholipid component of oxidized low-density lipoprotein (Ox-LDL), originates from the cleavage of phosphatidylcholine by phospholipase A2 (PLA2) and is catabolized to other substances by different enzymatic pathways. LPC exerts pleiotropic effects mediated by its receptors, G protein-coupled signaling receptors, Toll-like receptors, and ion channels to activate several second messengers. Lysophosphatidylcholine (LPC) is increasingly considered a key marker/factor positively in pathological states, especially inflammation and atherosclerosis development. Current studies have indicated that the injury of nervous tissues promotes oxidative stress and lipid peroxidation, as well as excessive accumulation of LPC, enhancing the membrane hyperexcitability to induce chronic pain, which may be recognized as one of the hallmarks of chronic pain. However, findings from lipidomic studies of LPC have been lacking in the context of chronic pain. In this review, we focus in some detail on LPC sources, biochemical pathways, and the signal-transduction system. Moreover, we outline the detection methods of LPC for accurate analysis of each individual LPC species and reveal the pathophysiological implication of LPC in chronic pain, which makes it an interesting target for biomarkers and the development of medicine regarding chronic pain.
Topics: Atherosclerosis; Chronic Pain; Humans; Lipoproteins, LDL; Lysophosphatidylcholines; Phospholipases A2; Receptors, G-Protein-Coupled; Signal Transduction
PubMed: 35955410
DOI: 10.3390/ijms23158274 -
Journal of Dairy Science Jan 2023Dairy consumption is inversely related to the risk of developing type 2 diabetes in epidemiological research. One proposed hypothesis is that phospholipid (PL) species... (Review)
Review
Graduate Student Literature Review: A scoping review on the impact of consumption of dairy products on phosphatidylcholine and lysophosphatidylcholine in circulation and the liver in human studies and animal models.
Dairy consumption is inversely related to the risk of developing type 2 diabetes in epidemiological research. One proposed hypothesis is that phospholipid (PL) species associated with dairy consumption mediate this relationship. This scoping review aimed to identify the existing literature in animal and human trials investigating the impact of dairy products, including milk, yogurt, and cheese as well as dairy-derived PL supplementation on PL and its species in the circulation, summarizing the characteristics of these studies and identifying research gaps. A systematic search was conducted across 3 databases (PubMed, Scopus, and Web of Science) in March 2021. Of 2,427 identified references, 15 studies (7 humans and 8 animal studies) met the eligibility criteria and were included in the final narrative synthesis. The evidence base was heterogeneous, involving a variety of clinical and preclinical studies, metabolically healthy or obese/diabetic participants or animal models, and displayed mixed findings. Circulating postprandial concentrations of total PL were elevated acutely but unchanged after longer intervention with dairy products. The PL concentration remained stable even after a high dosage of milk supplemented with dairy-derived PL, which may be related to increased fecal excretion; however, certain phosphatidylcholine (PC) or lysophosphatidylcholine species were increased in circulation by interventions. These include several PC species with 32 to 38 total carbons in addition to the dairy biomarkers C15:0 and C17:0. The results of this scoping review demonstrate a small body of literature indicating that dairy products can influence blood concentrations of PC and lysophosphatidylcholine species in both rodents and humans without alteration of total PL and PC. There is a lack of well-designed trials in humans and animals that explore the potential differences between individual dairy foods on PL species. In addition, trials to understand the bioactive properties of PC and lysophosphatidylcholine species on cardiometabolic risk are needed.
Topics: Animals; Humans; Dairy Products; Diabetes Mellitus, Type 2; Diet; Liver; Lysophosphatidylcholines; Milk; Models, Animal; Phosphatidylcholines; Students; Yogurt
PubMed: 36400621
DOI: 10.3168/jds.2022-21938 -
The Journal of Biological Chemistry Apr 1982Lysophosphatidylcholine (lysoPC) and cholesterol at 1:1 molar ratio form multilamellar and, on sonication, unilamellar liposomes in water. Calorimetric scannings of...
Lysophosphatidylcholine (lysoPC) and cholesterol at 1:1 molar ratio form multilamellar and, on sonication, unilamellar liposomes in water. Calorimetric scannings of varied mixtures in water give evidence for the existence of a 1:1 complex of the lipids. The permeability of the 1:1 bilayer against glycerol, at 22-42 degrees C, is lower than that of phosphatidylcholine-cholesterol bilayers; the energy of activation of permeation is 73% higher. This implies a low groundstate of the entropy of activation of permeation. Unilamellar lysoPC-cholesterol 1:1 liposomes, isolated by gel exclusion chromatography, are able to incorporate no more than 8 to 10% excess lysoPC and no additional cholesterol at all. Their physical parameters such a outer radius (14.8 nm) and bilayer thickness (4.2 nm) are between those reported for phosphatidylcholine vesicles and phosphatidylcholine-cholesterol vesicles. The outside-inside distribution of lysoPC in the small vesicles (determined by 31P-NMR) is 2.0. A comparison of 13C-NMR spectra of lysoPC (in 2H2O) and lysoPC-cholesterol vesicles shows that in the vesicles the signals for the carboxyl carbon of lysoPC as well as those for carbons 1 and 2 (and, partly, 3) of motional restriction in this region of the molecule. The low groundstate of the entropy of activation of permeation, and the immobilization of the glycerol moiety of the lysoPC, argue for a high degree of structural organization in the "hydrogen belt" regions of the lysoPC-cholesterol bilayer, and for lipid-lipid complexing via hydrogen bonding in these regions.
Topics: Calorimetry; Cholesterol; Glycerol; Kinetics; Liposomes; Lysophosphatidylcholines; Magnetic Resonance Spectroscopy; Molecular Conformation; Permeability; Thermodynamics
PubMed: 7061497
DOI: No ID Found -
The Journal of Allergy and Clinical... May 2023Timely medical intervention in severe cases of coronavirus disease 2019 (COVID-19) and better understanding of the disease's pathogenesis are essential for reducing...
BACKGROUND
Timely medical intervention in severe cases of coronavirus disease 2019 (COVID-19) and better understanding of the disease's pathogenesis are essential for reducing mortality, but early classification of severe cases and its progression is challenging.
OBJECTIVE
We investigated the levels of circulating phospholipid metabolites and their relationship with COVID-19 severity, as well as the potential role of phospholipids in disease progression.
METHODS
We performed nontargeted lipidomic analysis of plasma samples (n = 150) collected from COVID-19 patients (n = 46) with 3 levels of disease severity, healthy individuals, and subjects with metabolic disease.
RESULTS
Phospholipid metabolism was significantly altered in COVID-19 patients. Results of a panel of phosphatidylcholine (PC) and lysophosphatidylcholine (LPC) and of phosphatidylethanolamine and lysophosphatidylethanolamine (LPE) ratios were significantly correlated with COVID-19 severity, in which 16 phospholipid ratios were shown to distinguish between patients with severe disease, mild disease, and healthy controls, 9 of which were at variance with those in subjects with metabolic disease. In particular, relatively lower ratios of circulating (PC16:1/22:6)/LPC 16:1 and (PE18:1/22:6)/LPE 18:1 were the most indicative of severe COVID-19. The elevation of levels of LPC 16:1 and LPE 18:1 contributed to the changes of related lipid ratios. An exploratory functional study of LPC 16:1 and LPE 18:1 demonstrated their ability in causing membrane perturbation, increased intracellular calcium, cytokines, and apoptosis in cellular models.
CONCLUSION
Significant Lands cycle remodeling is present in patients with severe COVID-19, suggesting a potential utility of selective phospholipids with functional consequences in evaluating COVID-19's severity and pathogenesis.
Topics: Humans; Phospholipids; COVID-19; Lysophosphatidylcholines
PubMed: 36736798
DOI: 10.1016/j.jaci.2022.11.032 -
The Journals of Gerontology. Series A,... May 2022In this study, we investigated how the concentrations, pairwise correlations and ratios of 202 free circulating blood metabolites and lipids vary with age in a panel of...
In this study, we investigated how the concentrations, pairwise correlations and ratios of 202 free circulating blood metabolites and lipids vary with age in a panel of n = 1 882 participants with an age range from 48 to 94 years. We report a statistically significant sex-dependent association with age of a panel of metabolites and lipids involving, in women, linoleic acid, α-linoleic acid, and carnitine, and, in men, monoacylglycerols and lysophosphatidylcholines. Evaluating the association of correlations among metabolites and/or lipids with age, we found that phosphatidylcholines correlations tend to have a positive trend associated with age in women, and monoacylglycerols and lysophosphatidylcholines correlations tend to have a negative trend associated with age in men. The association of ratio between molecular features with age reveals that decanoyl-l-carnitine/lysophosphatidylcholine ratio in women "decrease" with age, while l-carnitine/phosphatidylcholine and l-acetylcarnitine/phosphatidylcholine ratios in men "increase" with age. These results suggest an age-dependent remodeling of lipid metabolism that induces changes in cell membrane bilayer composition and cell cycle mechanisms. Furthermore, we conclude that lipidome is directly involved in this age-dependent differentiation. Our results demonstrate that, using a comprehensive approach focused on the changes of concentrations and relationships of blood metabolites and lipids, as expressed by their correlations and ratios, it is possible to obtain relevant information about metabolic dynamics associated with age.
Topics: Aged; Aged, 80 and over; Carnitine; Female; Humans; Linoleic Acid; Lysophosphatidylcholines; Male; Monoglycerides; Phosphatidylcholines
PubMed: 34748631
DOI: 10.1093/gerona/glab335 -
Cell Death & Disease Oct 2022Noninflammatory clearance of dying cells by professional phagocytes, termed efferocytosis, is fundamental in both homeostasis and inflammatory fibrosis disease but has...
Noninflammatory clearance of dying cells by professional phagocytes, termed efferocytosis, is fundamental in both homeostasis and inflammatory fibrosis disease but has not been confirmed to occur in chronic pancreatitis (CP). Here, we investigated whether efferocytosis constitutes a novel regulatory target in CP and its mechanisms. PRSS1 transgenic (PRSS1) mice were treated with caerulein to mimic CP development. Phospholipid metabolite profiling and epigenetic assays were performed with PRSS1 CP models. The potential functions of Atp8b1 in CP model were clarified using Atp8b1-overexpressing adeno-associated virus, immunofluorescence, enzyme-linked immunosorbent assay(ELISA), and lipid metabolomic approaches. ATAC-seq combined with RNA-seq was then used to identify transcription factors binding to the Atp8b1 promoter, and ChIP-qPCR and luciferase assays were used to confirm that the identified transcription factor bound to the Atp8b1 promoter, and to identify the specific binding site. Flow cytometry was performed to analyze the proportion of pancreatic macrophages. Decreased efferocytosis with aggravated inflammation was identified in CP. The lysophosphatidylcholine (LPC) pathway was the most obviously dysregulated phospholipid pathway, and LPC and Atp8b1 expression gradually decreased during CP development. H3K27me3 ChIP-seq showed that increased Atp8b1 promoter methylation led to transcriptional inhibition. Atp8b1 complementation substantially increased the LPC concentration and improved CP outcomes. Bhlha15 was identified as a transcription factor that binds to the Atp8b1 promoter and regulates phospholipid metabolism. Our study indicates that the acinar Atp8b1/LPC pathway acts as an important "find-me" signal for macrophages and plays a protective role in CP, with Atp8b1 transcription promoted by the acinar cell-specific transcription factor Bhlha15. Bhlha15, Atp8b1, and LPC could be clinically translated into valuable therapeutic targets to overcome the limitations of current CP therapies.
Topics: Animals; Mice; Acinar Cells; Adenosine Triphosphatases; Ceruletide; Histones; Inflammation; Lysophosphatidylcholines; Macrophages; Pancreatitis, Chronic; Phospholipid Transfer Proteins; Transcription Factors
PubMed: 36273194
DOI: 10.1038/s41419-022-05322-6 -
Contrast Media & Molecular Imaging 2020
Topics: Animals; Iron; Lysophosphatidylcholines; Magnetic Resonance Imaging; Models, Animal; Molecular Imaging; Myelin Sheath
PubMed: 32140089
DOI: 10.1155/2020/5168147 -
Molecular Microbiology Sep 2021The lipid mediators, platelet-activating factor (PAF) and lysophosphatidylcholine (LPC), play relevant pathophysiological roles in Trypanosoma cruzi infection. Several...
The lipid mediators, platelet-activating factor (PAF) and lysophosphatidylcholine (LPC), play relevant pathophysiological roles in Trypanosoma cruzi infection. Several species of LPC, including C18:1 LPC, which mimics the effects of PAF, are synthesized by T. cruzi. The present study identified a receptor in T. cruzi, which was predicted to bind to PAF, and found it to be homologous to members of the progestin and adiponectin family of receptors (PAQRs). We constructed a three-dimensional model of the T. cruzi PAQR (TcPAQR) and performed molecular docking to predict the interactions of the TcPAQR model with C16:0 PAF and C18:1 LPC. We knocked out T. cruzi PAQR (TcPAQR) gene and confirmed the identity of the expressed protein through immunoblotting and immunofluorescence assays using an anti-human PAQR antibody. Wild-type and knockout (KO) parasites were also used to investigate the in vitro cell differentiation and interactions with peritoneal mouse macrophages; TcPAQR KO parasites were unable to react to C16:0 PAF or C18:1 LPC. Our data are highly suggestive that PAF and LPC act through TcPAQR in T. cruzi, triggering its cellular differentiation and ability to infect macrophages.
Topics: Amino Acid Sequence; Animals; Cell Differentiation; Chagas Disease; Gene Knockout Techniques; Host-Parasite Interactions; Humans; Lysophosphatidylcholines; Macrophages; Mice; Molecular Docking Simulation; Phylogeny; Platelet Activating Factor; Protein Conformation; Protozoan Proteins; Receptors, Adiponectin; Receptors, Progesterone; Trypanosoma cruzi
PubMed: 34184334
DOI: 10.1111/mmi.14778 -
ImmunoHorizons Apr 2021Lysophosphatidylcholine (LPC), a dominant lipid component of oxidized low-density lipoprotein, plays a major role in inflammation associated with atherosclerosis and...
Lysophosphatidylcholine (LPC), a dominant lipid component of oxidized low-density lipoprotein, plays a major role in inflammation associated with atherosclerosis and neurodegenerative disorders. It activates inflammatory responses from macrophages, neuronal cells, and endothelial cells. However, the exact mechanism by which LPC promotes inflammation remains incompletely understood. In this study, we show that the production of inflammatory cytokines and cytotoxicity with LPC are both critically dependent on its ability to bring about release of ATP from cells. The induction of caspase-1-mediated IL-1β release with LPC from TLR-primed mouse and human macrophages and mouse neuronal cells is reduced in the presence of ATP-hydrolyzing enzyme, apyrase, and the inhibitors of purinergic signaling. ATP released from LPC-treated cells also promotes an IL-12p70, low phagocytic, and poorly costimulatory phenotype in macrophages in a caspase-1-independent manner. Treatment with apyrase reduces production of inflammatory cytokines with LPC in vivo. These findings reveal a previously unappreciated pathway for the generation of inflammatory responses with LPC, and these have significant implications for therapeutic intervention in chronic inflammatory disorders promoted by this lipid.
Topics: Adenosine Triphosphate; Animals; Cells, Cultured; Endothelial Cells; Humans; Inflammation; Interleukin-12; Interleukin-1beta; Lysophosphatidylcholines; Macrophages; Mice; Mice, Inbred C57BL; Neurons; Signal Transduction; THP-1 Cells
PubMed: 33911018
DOI: 10.4049/immunohorizons.2100023