Phosphatidylcholine Levels Research Articles

Global Lipidomics Reveals the Lipid Composition Heterogeneity of Extracellular Vesicles from Drug-Resistant Leishmania

Background: The rise of drug-resistant Leishmania strains presents a significant challenge in the treatment of Leishmaniasis, a neglected tropical disease. Extracellular vesicles (EVs) produced by these parasites have gained attention for their role in drug resistance and host–pathogen interactions. Methods: This study developed and applied a novel lipidomics workflow to explore the lipid profiles of EVs from three types of drug-resistant Leishmania infatum strains compared to a wild-type strain. EVs were isolated through ultracentrifugation, and their lipid content was extracted using a modified Matyash protocol. LC-MS analysis was performed, and data processing in MS-DIAL enabled lipid identification and quantification. Statistical analysis in MetaboAnalyst revealed strain-specific lipid alterations, highlighting potential links between lipid composition and drug resistance mechanisms. Results: Our results show distinct alterations in lipid composition associated with drug resistance. Specifically, drug-resistant strains exhibited reduced levels of phosphatidylcholine (PC) and phosphatidylglycerol (PG), particularly in the amphotericin B-resistant strain LiAmB1000.1. Sterol and glycerolipid species, including cholesteryl ester (CE) and triacylglycerol (TG) were also found to be diminished in LiAmB1000.1. These changes suggest significant lipid remodeling under drug pressure, potentially altering the biophysical properties of EV membranes and their capacity for molecule transfer. Furthermore, the lipidomic profiles of EVs from the other resistant strains, LiSb2000.1 and LiMF200.5, also displayed unique alterations, underscoring strain-specific adaptations to different drug resistance mechanisms. Conclusions: These significant alterations in lipid composition suggest potential lipid-based mechanisms underlying drug resistance in Leishmania, providing new avenues for therapeutic intervention.

Clinical measures in chronic neuropathic pain are related to the Kennedy and endocannabinoid pathways.

Chronic neuropathic pain (CNP) is a debilitating condition, often refractory to currently available drugs. Understanding biochemical alterations in peripheral tissues such as blood will be useful for understanding underlying pathophysiological processes relating to CNP. We collected blood from two independent cohorts of CNP and pain-free controls (CNP n = 129/Controls n = 127) in the UK and Ireland to investigate the relationship between CNP-associated molecular/biochemical alterations and a range of clinical and pain metric parameters. Multiple statistical comparisons were conducted on the data, with selected variables included in one or more of the intended inferential analyses (six models). Gene expression analysis showed that choline phosphotransferase (CHPT1) was increased (p < .001) in the CNP group compared to controls. The levels of phosphatidylcholine, a metabolite of CHPT1 in the Kennedy Pathway, were significantly (p = .008) decreased in the plasma of patients with CNP. Given the relationship between the Kennedy pathway and endocannabinoids, plasma endocannabinoids and related N-acylethanolamines were quantified in clinical samples by HPLC-Tandem Mass Spectrometry. Plasma levels of the endocannabinoid 2-arachidonoylglycerol were higher in CNP samples compared to controls, and in the statistical models applied, 2-arachidonoylglycerol significantly increased the odds of CNP (p < .001). The expression of genes related to the synthesis and catabolism of endocannabinoids also corroborated the increased plasma 2-arachidonoylglycerol levels in patients with CNP. Endocannabinoid levels, expression of genes related to endocannabinoid metabolism, age, sex, depression and anxiety state together were strong predictors of CNP. The observed molecular changes indicate that lipid metabolism is altered in CNP and thus may represent a viable target for novel analgesics or biomarker development.

Remodeling of membrane lipids associated with ABA-induced desiccation tolerance in Physcomitrium patens

Pretreatment of Physcomitrium patens with abscisic acid (ABA) has been shown to induce desiccation tolerance. While previous research suggests that ABA-induced production of proteins and soluble sugars contributes to desiccation stress tolerance, additional mechanisms underlying this tolerance remain unclear. In this study, we found that ABA pretreatment led to increased levels of digalactosyl diacylglycerol (DGDG), phosphatidylcholine (PC), and phosphatidylinositol (PI), along with a decrease in monogalactosyl diacylglycerol (MGDG). These changes elevated the MGDG/DGDG and PC/phosphatidylethanolamine (PE) ratios, potentially stabilizing membranes and enhancing desiccation tolerance. Furthermore, ABA pretreatment effectively prevented membrane lipid degradation during desiccation and subsequent rehydration. These findings highlight ABA's role in desiccation tolerance through membrane lipid modulation, providing new insights into stress tolerance mechanisms in bryophytes.

Distribution of Dietary Phospholipids in Selected Agri-Foods: Versatile Nutraceutical Ingredients.

Phospholipids (PLs) play a crucial role in the nutraceutical field due to their various health benefits, including supporting acetylcholine production, enhancing cell membrane fluidity, and promoting cognitive functions. This study aimed to investigate the PL composition of selected agri-foods, including grains, vegetables, and fruits, and assess the effects of cooking methods. The major PLs identified in most agri-foods were phosphatidylethanolamine (PE) and phosphatidylcholine (PC). Additionally, lyso-phosphatidylethanolamine and lyso-phosphatidylcholine were found in rice, grains, and wheat, while N-acyl-phosphatidylethanolamine was detected in grains, wheat, and some vegetables. Phosphatidylinositol was present in fruits and vegetables, and phosphatidylserine was exclusively found in mushrooms. The PL composition was influenced by cooking methods, with boiling, steaming, blanching, and roasting increasing the PL content, while salting tended to decrease it. Although most agri-foods contained higher levels of PC than PE, citrus fruits under long-term low-temperature storage had significantly more PE than PC. This study established a PL database for the selected agri- and processed/cooked foods, providing insights into changes in PL composition and content based on cooking methods. Given the important health functions of each PL, consuming various agri-foods and incorporating different cooking methods for optimal health benefits is advisable.

Changes in the lipid balance in the gastric mucosa in rats under acute stress

BACKGROUND: Stress gastric ulcers are a type of peptic ulcer that develops in response to severe physiological or psychological stress. The causes of stress ulcers in the gaster have not yet been fully studied. AIM: To evaluate the composition of lipids in the gastric mucosa in rats under acute stress. MATERIALS AND METHODS: All rats included in the study (n=30) were divided into two groups. Group 1 (main group, n=20) included animals with a model of stress gastric ulcer created by stimulation with electrical impulses for 12 h. Group 2 (control group, n=10) included animals with no manipulations. At the end of the experiment, the effective and total concentration in blood serum of all animals was measured, followed by the calculation of the albumin binding reserve, and the plasma toxicity index. We also visually assessed the degree of damage to the gastric mucosa and determined the lipid composition. RESULTS: Our study showed that a stressful situation led to endogenous intoxication in group 1. A decrease in the level of phosphatidylcholine by 16.3% and phosphatidylserine by 18.6% in stressed rats demonstrates the destruction of the cell membrane associated with apoptosis, which macroscopically manifested as spot hemorrhages, erosions, and ulcers in the gastric mucosa. An increase in monoacylglycerol by 34.4% and diacylglycerol by 53.4% in group 1 indicates an increase in membrane permeability and induction of regenerative processes. CONCLUSION: In a stressful situation, a decrease in both total and effective albumin concentrations contributes to endogenous intoxication, leading to lipid imbalance, cell membrane damage, and the development of acute gastric mucosal injury.

High-coverage targeted lipidomics revealed novel profile of serum lipid dysregulation in adult growth hormone deficiency.

Patients with adult growth hormone deficiency (AGHD) are at increased risk of metabolic syndrome. Despite extensive research efforts in recent decades, the lipid metabolism pattern of AGHD has yet to be thoroughly characterized. In this study, we used lipidomics analysis of fasting serum samples from 30 AGHD patients due to intracranial germ cell tumors (iGCTs) and 30 age-, gender-, and body mass index (BMI)-matched healthy controls to investigate the serum lipidomic pattern of AGHD patients due to iGCTs. We meticulously quantified 534 serum lipids from 29 classes using high-coverage targeted lipidomics technology in conjunction with a robust bioinformatics pipeline. Our results revealed an AGHD-specific dynamic change in serum lipidomic profile, manifested by higher overall levels of many lipid subclasses, including triacylglycerols (TAGs), diacylglycerols (DAGs), phosphatidylglycerols, phosphatidylethanolamines (PE), phosphatidylcholines (PC), phosphatidylinositols, ceramides, and bis(monoacylglycerol)phosphates than in healthy controls, and a distinct lowering level in alkyl PE (PE-O) and alkyl PC (PC-O). AGHD individuals with non-alcoholic fatty liver disease showed specific changes in higher TAG and DAG subclass levels. Alterations in lipid profiles may contribute to metabolic dysregulation in AGHD patients. TAGs, PCs, and PE-fatty acids positively correlated with BMI, fasting insulin, insulin resistance index, and adverse lipid parameters. In contrast, ether-linked PE-O, PC-O, and LysoPE-O showed a negative correlation. This study has significantly expanded the current understanding of lipid dysregulation in AGHD patients due to iGCT. These findings can potentially guide future research and the development of monitoring and intervention strategies.

Role of double-negative autoreactive cells (CD4−CD8−) in phosphatidylcholine-mediated rheumatoid arthritis: A Mendelian randomization study

ObjectiveMendelian randomization (MR) was employed to explore the potential causal relationship between liposomes (LP) and rheumatoid arthritis (RA), with a focus on the mediating roles of immune cells (IC). MethodsBy screening public GWAS data, LP were used as exposure data, RA as outcome data, and IC as mediating factors. The Inverse Variance Weighted (IVW) method was the main analytical technique used in this paper to evaluate causal effects. Additional techniques included the MR-Egger, weighted median, weighted mode, and simple mode methods. Cochran's Q and MR-Egger were utilized for heterogeneity and multi-effect analysis. ResultsPhosphatidylcholine was revealed to enhance the risk of RA by MR analysis (P = 0.013, OR = 1.073, 95%CI = 1.015–1.136). There was no strong evidence that RA could affect liposome changes (IVW: P = 0.705, OR = 0.992, 95%CI = 0.952–1.034). The IVW method showed that increased levels of phosphatidylcholine were notably linked to higher levels of Double-Negative Autoreactive Cells (CD4−CD8−, DNAC) (P = 0.006, OR = 1.152, 95%CI = 1.041–1.276). The IVW approach showed that increased levels of DNAC were substantially linked to a higher risk of RA (P = 0.001, OR = 1.105, 95%CI = 1.041–1.173). Of the genetically predicted liposomes mediated by DNAC, 19.2 % were found. ConclusionThe present work established a causal association between LP and RA, and identified a potential mediating influence of IC. However, the specific mechanism of LP triacyl-glycerol and IC on RA is still unclear, and further research is needed.

Lipidomic profiling of serum and liver tissue reveals hepatoprotective mechanism of taxifolin in rats with CCl4-induced subacute hepatic injury based on LC-MS/MS

Currently, the hepatoprotective activity of taxifolin, a flavonoid isolated from Pseudotsuga taxifolia, has been reported in many animal models. However, whether the protective effect of taxifolin on the liver is related to its effect on lipidomics is unclear. Based on the significant therapeutic effect of taxifolin on CCl4 induced subacute hepatic injury, we observed the intervention of taxifolin by lipidomics. The results demonstrate that taxifolin can effectively reverse the damage caused by CCl4, which including hepatocyte vacuolization and necrosis. Lipomic profiling based on liquid chromatography-mass spectrometry showed that taxifolin was able to restore lipidomic changes caused by CCl4, including the levels of lysophosphatidylserine (LPS), phosphatidylcholine (PC), coenzyme (Co), phosphatidylglyceride (PG), phosphatidylserine (PS), dimethylphosphatidylethanolamine (dMePE), ceramide (Cer), sphingosine (So), triglycerides (TG), and monogalactosyl diacylglycerol (MGDG) in the rat liver, and phosphatidylcarbinol (PMe) and phosphatidylethanolamine (PE), plant sphingosine (phSM), glucose ceramide (CerG1), TG, and diglycerides (DG) in serum. Spearman's correlation analysis showed that CerG1, phSM, PE, and PMe in serum, and Cer, dMePE, PG, PS, So, TG, and MGDG in liver were positively correlated with serum levels of aspartate transaminase, alanine transaminase, and liver index; while TG, DG in serum, and Co, LPS, PC in liver were negatively correlated with the parameters. In total, 43 and 34 lipid molecules were altered by taxifolin treatment in the liver and serum, respectively, mainly including glycerophosphoglycerols, glycerophosphocholines, glycerophosphoethanolamines, and linoleic acids and derivatives. Our findings help to provide novel insights into the mechanism of the hepatoprotective effect of taxifolin from a lipidomics approach.

Age-dependent changes in visceral adiposity are associated with decreased plasma levels of DHEA-S in sigma-1 receptor knockout male mice

The sigma-1 receptor (S1R) is involved in intracellular lipid synthesis and transport. Recent studies have shown that its genetic inactivation impairs adipogenic differentiation in vitro. This study investigated the role of S1R in adipose tissue physiology and metabolic health using adult and old WT and S1R KO mice.Visceral fat mass was increased in adult, but not old S1R-KO male mice compared to that of WT mice, despite having similar body weights, food intake, and energy expenditure. The average adipocyte size was 64 % larger in adult KO mice than in adult WT mice. Adult S1R-KO mice showed reduced plasma dehydroepiandrosterone sulfate (DHEA-S) and elevated fasting plasma leptin concentrations. Lipidomic analysis revealed alterations in plasma metabolite concentrations, particularly reduced levels of sphingomyelins, ceramides, phosphatidylcholines, lysophosphatidylcholines, and cholesteryl esters in adult mice. Decreased expression of Pparγ, Adipoq, and Atgl was detected in visceral white adipose tissue (vWAT) isolated from adult KO mice. Additionally, Fabp4 and Adipoq expression levels were significantly lower in KO adipose-derived stromal cells than in WT adipose-derived stromal cells. A fivefold increase in the mitochondrial fatty acid oxidation rate and a 43 % increase in electron transfer coupling capacity were detected in adult S1R-KO vWAT.In summary, our investigation revealed an age-dependent association between increased visceral adiposity and decreased plasma levels of DHEA-S in S1R-deficient male mice. These findings underscore the potential role of S1R in regulating metabolic processes in adipose tissue and suggest that DHEA-S is a potential mediator of adiposity changes in the absence of S1R.

TM6SF2 E167K variant decreases PNPLA3-mediated PUFA transfer to promote hepatic steatosis and injury in MASLD.

Transmembrane 6 superfamily member 2 (TM6SF2) E167K variant is closely associated with the occurrence and development of metabolic dysfunction-associated steatotic liver disease (MASLD). However, the role and mechanism of TM6SF2 E167K variant during MASLD progression are not yet fully understood. The Tm6sf2167K knock-in (KI) mice were subjected to high-fat diet (HFD). Hepatic lipid levels of Tm6sf2167K KI mice were detected by lipidomics analysis. Thin-layer chromatography (TLC) was used to measure the newly synthesized triglyceride (TG) and phosphatidylcholine (PC). The TM6SF2 E167K variant significantly aggravated hepatic steatosis and injury in HFD-induced mice. Decreased polyunsaturated PC level and increased polyunsaturated TG level were found in liver tissue of HFD-induced Tm6sf2167K KI mice. Mechanistic studies demonstrated that the TM6SF2 E167K variant increased the interaction between TM6SF2 and PNPLA3, and impaired PNPLA3-mediated transfer of polyunsaturated fatty acids (PUFAs) from TG to PC. The TM6SF2 E167K variant increased the level of fatty acid-induced malondialdehyde and reactive oxygen species, and decreased fatty acid-downregulated cell membrane fluidity. Additionally, the TM6SF2 E167K variant decreased the level of hepatic PC containing C18:3, and dietary supplementation of PC containing C18:3 significantly attenuated the TM6SF2 E167K-induced hepatic steatosis and injury in HFD-fed mice. The TM6SF2 E167K variant could promote its interaction with PNPLA3 and inhibit PNPLA3-mediated transfer of PUFAs from TG to PC, resulting in the hepatic steatosis and injury during MASLD progression. PC containing C18:3 could act as a potential therapeutic supplement for MASLD patients carrying the TM6SF2 E167K variant.

Oxidised phosphatidylcholine induces sarcolemmal ceramide accumulation and insulin resistance in skeletal muscle.

Intracellular ceramide accumulation in specific cellular compartments is a potential mechanism explaining muscle insulin resistance in the pathogenesis of type 2 diabetes. Muscle sarcolemmal ceramide accumulation negatively impacts insulin sensitivity in humans, but the mechanism explaining this localised accumulation is unknown. Previous reports revealed that circulating oxidised LDL is elevated in serum of individuals with obesity and type 2 diabetes. Oxidised phosphatidylcholine, which is present in oxidised LDL, has previously been linked to ceramide pathway activation, and could contribute to localised ceramide accumulation in skeletal muscle. We hypothesised that oxidised phosphatidylcholine inversely correlates with insulin sensitivity in serum, and induces sarcolemmal ceramide accumulation and decreases insulin sensitivity in muscle. We used LC-MS/MS to quantify specific oxidised phosphatidylcholine species in serum from a cross-sectional study of 58 well-characterised individuals spanning the physiological range of insulin sensitivity. We also performed in vitro experiments in rat L6 myotubes interrogating the role of specific oxidised phosphatidylcholine species in promoting sarcolemmal ceramide accumulation, inflammation and insulin resistance in skeletal muscle cells. Human serum oxidised phosphatidylcholine levels are elevated in individuals with obesity and type 2 diabetes, inversely correlated with insulin sensitivity, and positively correlated with sarcolemmal C18:0 ceramide levels in skeletal muscle. Specific oxidised phosphatidylcholine species, particularly 1-palmitoyl-2-(5-oxovaleroyl)-sn-glycero-3-phosphocholine (POVPC), increase total ceramide and dihydroceramide and decrease total sphingomyelin in the sarcolemma of L6 myotubes by de novo ceramide synthesis and sphingomyelinase activation. POVPC also increases inflammatory signalling and causes insulin resistance in L6 myotubes. These data suggest that circulating oxidised phosphatidylcholine species promote ceramide accumulation and decrease insulin sensitivity in muscle, help explain localised sphingolipid accumulation and muscle inflammatory response, and highlight oxidised phosphatidylcholine species as potential targets to combat insulin resistance.

Causal relationship between Lipdome and Chronic Obstructive Pulmonary Disease and Asthma: Mendelian randomization

Genetic risk significantly influence susceptibility and heterogeneity of chronic obstructive pulmonary disease (COPD) and asthma, and increasing evidence suggests their close association with lipdome. However, their causal relationship remains unclear. In this study, we conducted a two-sample MR (Mendelian randomization) analysis using publicly available large-scale genome-wide association studies (GWAS) data to evaluate the causal impact of lipdome on COPD and asthma. The inverse variance weighted (IVW) method served as the primary analysis method, and multiple sensitivity and heterogeneity tests were performed to assess the reliability of the results. Finally, a Meta-analysis was conducted on lipdome with significant causal relationships to validate the robustness of the results. Our findings suggest that Sterol ester (27:1/18:2), Phosphatidylcholine (15:0_18:2), (16:0_18:2), (16:0_20:2), (17:0_18:2), (18:1_18:1), (18:1_18:2), (18:1_20:2), Triacylglycerol (54:3), and (56:4) levels are protective factors for COPD, while levels of Phosphatidylcholine (16:0_22:5), (18:0_20:4), and (O-16:0_20:4) are risk factors for COPD. Meta-analysis of lipids causally related to COPD also indicates significant results. Phosphatidylcholine (16:0_20:4), (16:0_22:5), and (18:0_20:4) levels are risk factors for asthma, while Phosphatidylcholine (18:1_18:2), (18:1_20:2), and Sphingomyelin (d38:1) levels are protective factors for asthma. However, the lack of statistical significance in the Meta-analysis may be due to heterogeneity in research methods and data statistics. This study indicates that 4 lipdome species have significant correlations with COPD and asthma. Phosphatidylcholine (18:1_18:2) and (18:1_20:2) are protective factors, while Phosphatidylcholine (16:0_22:5) and (18:0_20:4) are risk factors. Additionally, due to differences in molecular subtypes, phosphatidylcholine, sterol ester, and triacylglycerol exhibit differential effects on the diseases.

Phosphatidylcholine's influence on Dysmenorrhea: conclusive insights from Mendelian randomization analysis.

This study aimed to investigate the causal relationship between phosphatidylcholine (PC) levels and dysmenorrhea using Mendelian randomization (MR) analysis. We conducted a two-sample MR analysis using GWAS data on PC levels and dysmenorrhea. Single nucleotide polymorphisms (SNPs) associated with PC levels were used as instrumental variables. MR-Egger regression and inverse variance weighting (IVW) were used to estimate the causal effect of PC levels on dysmenorrhea. Sensitivity analyses were performed to assess the robustness of the results. The IVW analysis revealed a significant positive association between higher PC levels and dysmenorrhea (OR: 1.533, 95% CI: 1.039-2.262, P = 0.031). The MR-Egger regression did not detect pleiotropy. Sensitivity analyses confirmed the robustness of the results. This study provides evidence suggesting a causal link between increased PC levels and dysmenorrhea. Further research is needed to understand the biological mechanisms underlying this relationship and to explore potential therapeutic implications.

Exploratory Metabolomics and Lipidomics Profiling Contributes to Understanding How Curcumin Improves Quality of Goat Semen Stored at 16 °C in Tropical Areas.

Reactive oxygen species (ROS) exert a vital role in sperm quality during semen preservation, where excessive ROS leads to oxidative damage and undermines sperm integrity. Curcumin, a botanical extract, is capable of neutralizing ROS and enhancing the activity of antioxidant enzymes. This study was aimed at evaluating the effects of curcumin on sperm viability, acrosome integrity, and antioxidant levels, as well as metabolomic and lipidomic profiles. The results demonstrated that curcumin at 25 µmol/L significantly enhanced sperm motility, plasma membrane, and acrosome integrity, elevated the levels of antioxidant enzymes (T-AOC, CAT, SOD), and decreased ROS production (p < 0.05). Metabolomic analysis identified 93 distinct metabolites that showed significant differences between the control and curcumin-treated groups. KEGG pathways emphasized the participation of these metabolites in key metabolic processes such as the citric acid cycle, cholesterol metabolism, and fatty acid metabolism. Curcumin treatment brought about notable variations in lipid profiles, including increased levels of phosphatidylcholine, acylcarnitine, and triglyceride over the storage time, suggesting enhanced lipid anabolic activity. Overall, the supplementation of curcumin at 25 µmol/L effectively mitigates oxidative stress and prolongs the viability of semen storage at 16 °C by modulating specific metabolic and lipid profiles.

Exploring the causal effects of serum lipids and lipidomes on lewy body dementia: a Mendelian randomization study.

Lewy body dementia (LBD) is a neurodegenerative disorder characterized by the accumulation of Lewy bodies, which primarily composed of misfolded alpha-synuclein (αS). The development of LBD and APOE4 subtypes is thought to be associated with disorders of lipid metabolism. In this study, we investigated the causal relationship between serum lipids, liposomes and LBD using a two-sample Mendelian randomization (TSMR) method. A TSMR analysis of genome-wide association study (GWAS) data for 8 serum lipids, 179 lipidomes components, LBD and its subtypes was performed, using inverse variance weighted as the primary outcome. To ensure robustness, the sensitivity analyses including MR Pleiotropy RESidual Sum and Outlier, Cochran's test, leave-one-out method and funnel plots were performed. In this study, we found that low-density lipoprotein cholesterol (LDL-C) (OR=1.45, 95% CI=1.19-1.77, P<0.001) and remnant cholesterol (RC) (OR=2.64, 95% CI=1.64-4.28, P<0.001) had significant positive causal effects on LBD, and RC also had a positive effect on LBD in carriers of the APOE4 gene. The results of lipidome analysis showed that phosphatidylcholine (PC) (O-16:0_20:4) levels (OR=0.86, 95% CI=0.75-0.98, P=0.02) and PC (O-18:1_20:4) levels (OR=0.76, 95% CI=0.65-0.89, P <0.001) had negative causal effects on LBD, whereas phosphatidylinositol (PI) (18:1_20:4) levels had a positive causal effect on LBD (OR=1.19, 95% CI=1.02-1.39, P=0.03). For LBD with APOE4 carriers, high levels of PC (16:1_18:0) and PC (O-18:2_18:1) had a significant positive effect, while high levels of PC (O-16:1_18:0), phosphatidylethanolamine (PE) (O-18:2_18:1), sphingomyelin (SM) (d38:2), and triacylglycerol (TAG) (56:5) significantly reduced the risk. No heterogeneity and horizontal pleiotropy were observed in sensitivity analysis. Elevated LDL-C and RC levels are significant risk factors for LBD, with RC also impacting APOE4-carrying LBD. Glycerophospholipids play a crucial role in the pathogenesis of LBD, but the specific components that play a role differ from those with the APOE4 carries. These findings highlight the importance of lipid metabolism in LBD and APOE4 subtypes.

Arabidopsis trigalactosyldiacylglycerol1 mutants reveal a critical role for phosphtidylcholine remodeling in lipid homeostasis.

Lipid remodeling plays a critical role in plant response to abiotic stress and metabolic perturbations. Key steps in this process involve modifications of phosphatidylcholine (PC) acyl chains mediated by lysophosphatidylcholine: acyl-CoA acyltransferases (LPCATs) and phosphatidylcholine: diacylglycerol cholinephosphotransferase (ROD1). To assess their importance in lipid homeostasis, we took advantage of the trigalactosyldiacylglycerol1 (tgd1) mutant that exhibits marked increases in fatty acid synthesis and fatty acid flux through PC due to a block in inter-organelle lipid trafficking. Here, we showed that the increased fatty acid synthesis in tgd1 is due to posttranslational activation of the plastidic acetyl-coenzyme A carboxylase. Genetic analysis showed that knockout of LPCAT1 and 2 resulted in a lethal phenotype in tgd1. In addition, plants homozygous for lpcat2 and heterozygous for lpcat1 in the tgd1 background showed reduced levels of PC and triacylglycerols (TAG) and alterations in their fatty acid profiles. We further showed that disruption of ROD1 in tgd1 resulted in changes in fatty acid composition of PC and TAG, decreased leaf TAG content and reduced seedling growth. Together, our results reveal a critical role of LPCATs and ROD1 in maintaining cellular lipid homeostasis under conditions, in which fatty acid production largely exceeds the cellular demand for membrane lipid synthesis.

Transamniotic Delivery of Surfactant Protein B mRNA in a Healthy Model

Introduction: We sought to determine whether exogenous surfactant protein B (SPB) mRNA could be incorporated and translated by the fetal lung after simple transamniotic administration. Methods: Fetuses (n = 149) of twelve time-dated dams underwent intra-amniotic injections of either human SPB (hSPB) mRNA encapsulated into lipopolyplex (mRNA, n = 99) or lipopolyplex without mRNA (control; n = 50) on gestational day 17 (E17, term = E21–22). Lungs were screened for hSPB by enzyme-linked immunosorbent assay daily until term. Phosphatidylcholine (PC) (a surrogate for surfactant production) was measured in the amniotic fluid by fluorometric assay. Statistical analysis included nonparametric Wilcoxon rank sum test. Results: Significantly improved survival in the mRNA group compared to controls was observed at E18 (100% vs. 85.7%) and E20 (100% vs. 83.3%) (both p < 0.001). When controlled by mRNA-free injections, hSPB protein was detected in the mRNA group’s lungs at E18, 19, and term (p = 0.002 to <0.001). Amniotic fluid PC levels were increased compared to control at term [285.9 (251.1, 363.9) μM versus 263.1 (222.8, 309.1) μM]; however, this did not reach significance (p = 0.33). Conclusions: Encapsulated exogenous SPB mRNA can be incorporated and translated by fetal lung cells following intra-amniotic injection in a healthy rat model. Transamniotic mRNA delivery could become a novel strategy for perinatal surfactant protein replacement.

Mechanisms insights into bisphenol S-induced oxidative stress, lipid metabolism disruption, and autophagy dysfunction in freshwater crayfish

Bisphenol S (BPS) is widely used in plastic products, food packaging, electronic products, and other applications. In recent years, BPS emissions have increasingly impacted aquatic ecosystems. The effects of BPS exposure on aquatic animal health have been documented; however, our understanding of its toxicology remains limited. This study aimed to explore the mechanisms of lipid metabolism disorders, oxidative stress, and autophagy dysfunction induced in freshwater crayfish (Procambarus clarkii) by exposure to different concentrations of BPS (0 µg/L, 1 µg/L, 10 µg/L, and 100 µg/L) over 14 d. The results indicated that BPS exposure led to oxidative stress by inducing elevated levels of reactive oxygen species (ROS) and inhibiting the activity of antioxidant-related enzymes. Additionally, BPS exposure led to increased lipid content in the serum and hepatopancreas, which was associated with elevated lipid-related enzyme activity and increased expression of related genes. Furthermore, BPS exposure decreased levels of phosphatidylcholine (PC) and phosphatidylinositol (PI), disrupted glycerophospholipid (GPI) metabolism, and caused lipid deposition in the hepatopancreatic. These phenomena may have occurred because BPS exposure reduced the transport of fatty acids and led to hepatopancreatic lipid deposition by inhibiting the transport and synthesis of PC and PI in the hepatopancreas, thereby inhibiting the PI3K-AMPK pathway. In conclusion, BPS exposure induced oxidative stress, promoted lipid accumulation, and led to autophagy dysfunction in the hepatopancreas of freshwater crayfish. Collectively, our findings provide the first evidence that environmentally relevant levels of BPS exposure can induce hepatopancreatic lipid deposition through multiple pathways, raising concerns about the potential population-level harm of BPS and other bisphenol analogues.

Alterations in Choline Metabolism in Non-Obese Individuals with Insulin Resistance and Type 2 Diabetes Mellitus.

The prevalence of non-obese individuals with insulin resistance (IR) and type 2 diabetes (T2D) is increasing worldwide. This study investigates the metabolic signature of phospholipid-associated metabolites in non-obese individuals with IR and T2D, aiming to identify potential biomarkers for these metabolic disorders. The study cohort included non-obese individuals from the Qatar Biobank categorized into three groups: insulin sensitive, insulin resistant, and patients with T2D. Each group comprised 236 participants, totaling 708 individuals. Metabolomic profiling was conducted using high-resolution mass spectrometry, and statistical analyses were performed to identify metabolites associated with the progression from IS to IR and T2D. The study observed significant alterations in specific phospholipid metabolites across the IS, IR, and T2D groups. Choline phosphate, glycerophosphoethanolamine, choline, glycerophosphorylcholine (GPC), and trimethylamine N-oxide showed significant changes correlated with disease progression. A distinct metabolic signature in non-obese individuals with IR and T2D was characterized by shifts in choline metabolism, including decreased levels of choline and trimethylamine N-oxide and increased levels of phosphatidylcholines, phosphatidylethanolamines, and their degradation products. These findings suggest that alterations in choline metabolism may play a critical role in the development of glucose intolerance and insulin resistance. Targeting choline metabolism could offer potential therapeutic strategies for treating T2D. Further research is needed to validate these biomarkers and understand their functional significance in the pathogenesis of IR and T2D in non-obese populations.

The Food Sources in Western Diets Modulate Obesity Development, Insulin Sensitivity, and the Plasma and Cecal Metabolome in Mice.

Dietary constituents modulate development of obesity and type 2 diabetes. The metabolic impact from different food sources in western diets (WD) on obesity development is not fully elucidated. This study aims to identify dietary sources that differentially affect obesity development and the metabolic processes involved. Mice were fed isocaloric WDs with protein and fat from different food groups, including egg and dairy, terrestrial meat, game meat, marine, vegetarian, and a mixture of all. This study evaluates development of obesity, glucose tolerance, insulin sensitivity, and plasma and cecal metabolome. WD based on marine or vegetarian food sources protects male mice from obesity development and insulin resistance, whereas meat-based diets promote obesity. The intake of different food sources induces marked differences in the lipid-related plasma metabolome, particularly impacting phosphatidylcholines. Fifty-nine lipid-related plasma metabolites are positively associated with adiposity and a distinct cecal metabolome is found in mice fed a marine diet. This study demonstrates differences in obesity development between the food groups. Diet specific metabolomic signatures in plasma and cecum associated with adiposity, where a marine based diet modulates the level of plasma and cecal phosphatidylcholines in addition to preventing obesity development.