-
Nutrients Dec 2018Coffee is widely consumed and contains many bioactive compounds, any of which may impact pathways related to disease development. Our objective was to identify...
Coffee is widely consumed and contains many bioactive compounds, any of which may impact pathways related to disease development. Our objective was to identify individual lipid changes in response to coffee drinking. We profiled the lipidome of fasting serum samples collected from a previously reported single blinded, three-stage clinical trial. Forty-seven habitual coffee consumers refrained from drinking coffee for 1 month, consumed 4 cups of coffee/day in the second month and 8 cups/day in the third month. Samples collected after each coffee stage were subject to quantitative lipidomic profiling using ion-mobility spectrometry⁻mass spectrometry. A total of 853 lipid species mapping to 14 lipid classes were included for univariate analysis. Three lysophosphatidylcholine (LPC) species including LPC (20:4), LPC (22:1) and LPC (22:2), significantly decreased after coffee intake ( < 0.05 and < 0.05). An additional 72 species mapping to the LPC, free fatty acid, phosphatidylcholine, cholesteryl ester and triacylglycerol classes of lipids were nominally associated with coffee intake ( < 0.05 and > 0.05); 58 of these decreased after coffee intake. In conclusion, coffee intake leads to lower levels of specific LPC species with potential impacts on glycerophospholipid metabolism more generally.
Topics: Adult; Caffeine; Cholesterol Esters; Coffea; Coffee; Diet; Drinking; Fatty Acids, Nonesterified; Glycerophospholipids; Humans; Lipid Metabolism; Lysophosphatidylcholines; Mass Spectrometry; Phosphatidylcholines; Plant Preparations; Triglycerides
PubMed: 30513727
DOI: 10.3390/nu10121851 -
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 -
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 -
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 -
Investigative Ophthalmology & Visual... Aug 2022The etiology of exfoliation glaucoma (XFG) is poorly understood. We aimed to identify a prediagnostic plasma metabolomic signature associated with XFG.
PURPOSE
The etiology of exfoliation glaucoma (XFG) is poorly understood. We aimed to identify a prediagnostic plasma metabolomic signature associated with XFG.
METHODS
We conducted a 1:1 matched case-control study nested within the Nurses' Health Study and Health Professionals Follow-up Study. We collected blood samples in 1989-1990 (Nurses' Health Study) and 1993-1995 (Health Professionals Follow-up Study). We identified 205 incident XFG cases through 2016 (average time to diagnosis from blood draw = 11.8 years) who self-reported glaucoma and were confirmed as XFG cases with medical records. We profiled plasma metabolites using liquid chromatography-mass spectrometry. We evaluated 379 known metabolites (transformed for normality using probit scores) using multiple conditional logistic models. Metabolite set enrichment analysis was used to identify metabolite classes associated with XFG. To adjust for multiple comparisons, we used number of effective tests (NEF) and the false discovery rate (FDR).
RESULTS
Mean age of cases (n = 205) at diagnosis was 71 years; 85% were women and more than 99% were Caucasian; controls (n = 205) reported eye examinations as of the matched cases' index date. Thirty-three metabolites were nominally significantly associated with XFG (P < 0.05), and 4 metabolite classes were FDR-significantly associated. We observed positive associations for lysophosphatidylcholines (FDR = 0.02) and phosphatidylethanolamine plasmalogens (FDR = 0.004) and inverse associations for triacylglycerols (FDR < 0.0001) and steroids (FDR = 0.03). In particular, the multivariable-adjusted odds ratio with each 1 standard deviation higher plasma cortisone levels was 0.49 (95% confidence interval, 0.32-0.74; NEF = 0.05).
CONCLUSIONS
In plasma from a decade before diagnosis, lysophosphatidylcholines and phosphatidylethanolamine plasmalogens were positively associated and triacylglycerols and steroids (e.g., cortisone) were inversely associated with XFG risk.
Topics: Aged; Case-Control Studies; Cortisone; Exfoliation Syndrome; Female; Follow-Up Studies; Humans; Lysophosphatidylcholines; Male; Metabolomics; Phosphatidylethanolamines; Plasmalogens; Triglycerides
PubMed: 35951322
DOI: 10.1167/iovs.63.9.15 -
Clinical and Translational Medicine Oct 2022A heterogeneous clinical phenotype is a characteristic of coronavirus disease 2019 (COVID-19). Therefore, investigating biomarkers associated with disease severity is...
BACKGROUND
A heterogeneous clinical phenotype is a characteristic of coronavirus disease 2019 (COVID-19). Therefore, investigating biomarkers associated with disease severity is important for understanding the mechanisms responsible for this heterogeneity and for developing novel agents to prevent critical conditions. This study aimed to elucidate the modulations of sphingolipids and glycerophospholipids, which have been shown to possess potent biological properties.
METHODS
We measured the serum sphingolipid and glycerophospholipid levels in a total of 887 samples from 215 COVID-19 subjects, plus 115 control subjects without infectious diseases and 109 subjects with infectious diseases other than COVID-19.
RESULTS
We observed the dynamic modulations of sphingolipids and glycerophospholipids in the serum of COVID-19 subjects, depending on the time course and severity. The elevation of C16:0 ceramide and lysophosphatidylinositol and decreases in C18:1 ceramide, dihydrosphingosine, lysophosphatidylglycerol, phosphatidylglycerol and phosphatidylinositol were specific to COVID-19. Regarding the association with maximum severity, phosphatidylinositol and phosphatidylcholine species with long unsaturated acyl chains were negatively associated, while lysophosphatidylethanolamine and phosphatidylethanolamine were positively associated with maximum severity during the early phase. Lysophosphatidylcholine and phosphatidylcholine had strong negative correlations with CRP, while phosphatidylethanolamine had strong positive ones. C16:0 ceramide, lysophosphatidylcholine, phosphatidylcholine and phosphatidylethanolamine species with long unsaturated acyl chains had negative correlations with D-dimer, while phosphatidylethanolamine species with short acyl chains and phosphatidylinositol had positive ones. Several species of phosphatidylcholine, phosphatidylethanolamine and sphingomyelin might serve as better biomarkers for predicting severe COVID-19 during the early phase than CRP and D-dimer. Compared with the lipid modulations seen in mice treated with lipopolysaccharide, tissue factor, or histone, the lipid modulations observed in severe COVID-19 were most akin to those in mice administered lipopolysaccharide.
CONCLUSION
A better understanding of the disturbances in sphingolipids and glycerophospholipids observed in this study will prompt further investigation to develop laboratory testing for predicting maximum severity and/or novel agents to suppress the aggravation of COVID-19.
Topics: Animals; Biomarkers; COVID-19; Ceramides; Glycerophospholipids; Histones; Lipopolysaccharides; Lysophosphatidylcholines; Mice; Phosphatidylcholines; Phosphatidylethanolamines; Phosphatidylglycerols; Phosphatidylinositols; Sphingolipids; Sphingomyelins; Thromboplastin
PubMed: 36214754
DOI: 10.1002/ctm2.1069 -
Molecules (Basel, Switzerland) Mar 2023Long-chain omega-3 fatty acids esterified in lysophosphatidylcholine (LPC-omega-3) are the most bioavailable omega-3 fatty acid form and are considered important for... (Review)
Review
Long-chain omega-3 fatty acids esterified in lysophosphatidylcholine (LPC-omega-3) are the most bioavailable omega-3 fatty acid form and are considered important for brain health. Lysophosphatidylcholine is a hydrolyzed phospholipid that is generated from the action of either phospholipase PLA or PLA. There are two types of LPC; 1-LPC (where the omega-3 fatty acid at the -2 position is acylated) and 2-LPC (where the omega-3 fatty acid at the -1 position is acylated). The 2-LPC type is more highly bioavailable to the brain than the 1-LPC type. Given the biological and health aspects of LPC types, it is important to understand the structure, properties, extraction, quantification, functional role, and effect of the processing of LPC. This review examines various aspects involved in the extraction, characterization, and quantification of LPC. Further, the effects of processing methods on LPC and the potential biological roles of LPC in health and wellbeing are discussed. DHA-rich-LysoPLs, including LPC, can be enzymatically produced using lipases and phospholipases from wide microbial strains, and the highest yields were obtained by Lipozyme RM-IM, Lipozyme TL-IM, and Novozym 435. Terrestrial-based phospholipids generally contain lower levels of long-chain omega-3 PUFAs, and therefore, they are considered less effective in providing the same health benefits as marine-based LPC. Processing (e.g., thermal, fermentation, and freezing) reduces the PL in fish. LPC containing omega-3 PUFA, mainly DHA (C22:6 omega-3) and eicosapentaenoic acid EPA (C20:5 omega-3) play important role in brain development and neuronal cell growth. Additionally, they have been implicated in supporting treatment programs for depression and Alzheimer's. These activities appear to be facilitated by the acute function of a major facilitator superfamily domain-containing protein 2 (Mfsd2a), expressed in BBB endothelium, as a chief transporter for LPC-DHA uptake to the brain. LPC-based delivery systems also provide the opportunity to improve the properties of some bioactive compounds during storage and absorption. Overall, LPCs have great potential for improving brain health, but their safety and potentially negative effects should also be taken into consideration.
Topics: Animals; Lysophosphatidylcholines; Brain; Fatty Acids, Omega-3; Membrane Transport Proteins; Biological Transport; Eicosapentaenoic Acid; Phospholipids; Fatty Acids; Docosahexaenoic Acids
PubMed: 37049852
DOI: 10.3390/molecules28073088 -
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 -
Molecular Metabolism Jun 2023Hepatic triacylglycerol accumulation and insulin resistance are key features of NAFLD. However, NAFLD development and progression are rather triggered by the aberrant...
OBJECTIVE
Hepatic triacylglycerol accumulation and insulin resistance are key features of NAFLD. However, NAFLD development and progression are rather triggered by the aberrant generation of lipid metabolites and signaling molecules including diacylglycerol (DAG) and lysophosphatidylcholine (lysoPC). Recent studies showed decreased expression of carboxylesterase 2 (CES2) in the liver of NASH patients and hepatic DAG accumulation was linked to low CES2 activity in obese individuals. The mouse genome encodes several Ces2 genes with Ces2a showing highest expression in the liver. Herein we investigated the role of mouse Ces2a and human CES2 in lipid metabolism in vivo and in vitro.
METHODS
Lipid metabolism and insulin signaling were investigated in mice lacking Ces2a and in a human liver cell line upon pharmacological CES2 inhibition. Lipid hydrolytic activities were determined in vivo and from recombinant proteins.
RESULTS
Ces2a deficient mice (Ces2a-ko) are obese and feeding a high-fat diet (HFD) provokes severe hepatic steatosis and insulin resistance together with elevated inflammatory and fibrotic gene expression. Lipidomic analysis revealed a marked rise in DAG and lysoPC levels in the liver of Ces2a-ko mice fed HFD. Hepatic lipid accumulation in Ces2a deficiency is linked to lower DAG and lysoPC hydrolytic activities in liver microsomal preparations. Moreover, Ces2a deficiency significantly increases hepatic expression and activity of MGAT1, a PPAR gamma target gene, suggesting aberrant lipid signaling upon Ces2a deficiency. Mechanistically, we found that recombinant Ces2a and CES2 show significant hydrolytic activity towards lysoPC (and DAG) and pharmacological inhibition of CES2 in human HepG2 cells largely phenocopies the lipid metabolic changes present in Ces2a-ko mice including reduced lysoPC and DAG hydrolysis, DAG accumulation and impaired insulin signaling.
CONCLUSIONS
Ces2a and CES2 are critical players in hepatic lipid signaling likely via the hydrolysis of DAG and lysoPC at the ER.
Topics: Humans; Mice; Animals; Insulin Resistance; Non-alcoholic Fatty Liver Disease; Lysophosphatidylcholines; Diglycerides; Insulin; Obesity
PubMed: 37059417
DOI: 10.1016/j.molmet.2023.101725 -
Cancer Discovery May 2019Pancreatic ductal adenocarcinoma (PDAC) develops a pronounced stromal response reflecting an aberrant wound-healing process. This stromal reaction features...
Pancreatic ductal adenocarcinoma (PDAC) develops a pronounced stromal response reflecting an aberrant wound-healing process. This stromal reaction features transdifferentiation of tissue-resident pancreatic stellate cells (PSC) into activated cancer-associated fibroblasts, a process induced by PDAC cells but of unclear significance for PDAC progression. Here, we show that PSCs undergo a dramatic lipid metabolic shift during differentiation in the context of pancreatic tumorigenesis, including remodeling of the intracellular lipidome and secretion of abundant lipids in the activated, fibroblastic state. Specifically, stroma-derived lysophosphatidylcholines support PDAC cell synthesis of phosphatidylcholines, key components of cell membranes, and also facilitate production of the potent wound-healing mediator lysophosphatidic acid (LPA) by the extracellular enzyme autotaxin, which is overexpressed in PDAC. The autotaxin-LPA axis promotes PDAC cell proliferation, migration, and AKT activation, and genetic or pharmacologic autotaxin inhibition suppresses PDAC growth . Our work demonstrates how PDAC cells exploit the local production of wound-healing mediators to stimulate their own growth and migration. SIGNIFICANCE: Our work highlights an unanticipated role for PSCs in producing the oncogenic LPA signaling lipid and demonstrates how PDAC tumor cells co-opt the release of wound-healing mediators by neighboring PSCs to promote their own proliferation and migration...
Topics: Animals; Carcinoma, Pancreatic Ductal; Cell Movement; Cell Proliferation; Disease Models, Animal; Disease Progression; Female; Humans; Lysophosphatidylcholines; Male; Mice, Inbred C57BL; Mice, Nude; Pancreatic Neoplasms; Pancreatic Stellate Cells; Phosphoric Diester Hydrolases; Signal Transduction; Stromal Cells; Tumor Cells, Cultured; Xenograft Model Antitumor Assays
PubMed: 30837243
DOI: 10.1158/2159-8290.CD-18-1212