Lipidomic Analysis Research Articles

A novel protein encoded by porcine circANKRD17 activates the PPAR pathway to regulate intramuscular fat metabolism

BackgroundIntramuscular fat is an important factor in evaluating pork quality and varies widely among different pig breeds. However, the regulatory mechanism of circular RNAs (circRNAs) in lipid metabolism remains largely unexplored.ResultsWe combined circRNA-seq and Ribo-seq data to screen a total of 18 circRNA candidates with coding potential, and circANKRD17 was found to be significantly elevated in the longissimus dorsi muscle of Lantang piglets, with a length of 1,844 nucleotides. Using single-cell sequencing, we identified 477 differentially expressed genes in IMF cells between Lantang and Landrace piglets, with enrichment in the PPAR signaling pathway. These genes included FABP4, FABP5, CPT1A, and UBC, consistent with the high levels of acylcarnitines observed in the longissimus dorsi muscles of the Lantang breed, as determined by lipidomic analysis. Further in vitro and in vivo experiments indicated that circANKRD17 can regulate lipid metabolism through various mechanisms involving the PPAR pathway, including promoting adipocyte differentiation, fatty acid transport and metabolism, triglyceride synthesis, and lipid droplet formation and maturation. In addition, we discovered that circANKRD17 has an open reading frame and can be translated into a novel 571-amino-acid protein that promotes lipid metabolism.ConclusionsOur research provides new insights into the role of protein-coding circANKRD17, especially concerning the metabolic characteristics of pig breeds with higher intramuscular fat content.

Multi-omics profiling in spinal muscular atrophy (SMA): investigating lipid and metabolic alterations through longitudinal CSF analysis of Nusinersen-treated patients.

Spinal muscular atrophy (SMA) is a rare neuromuscular disease caused by biallelic mutations in the SMN1 gene, leading to progressive muscle weakness due to degeneration of the anterior horn cells. Since 2017, SMA patients can be treated with the anti-sense oligonucleotide Nusinersen, which promotes alternative splicing of the SMN2 gene, by regular intrathecal injections. In this prospective study, we applied metabolomic, lipidomic, and proteomic analysis to examine sequential CSF samples from 13 SMA patients and controls. This multi-omic approach identified over 800 proteins and 400 small molecules including lipids. Multivariate analysis of multi-omic data successfully discriminated between the CSF derived from SMA patients and control subjects. Lipidomic analysis revealed increased levels of cholesteryl esters and lyso-phospholipids, along with reduced levels of cholesterol and phospholipids in the CSF of SMA patients as compared to healthy controls. These data, combined with results from functional assays, led us to conclude that SMA patients exhibit altered levels and function of high-density-lipoprotein (HDL)-like particles in the CSF. Notably, Nusinersen therapy was observed to reverse disease-specific profile changes toward a physiological state, potentially explicable by restoring HDL function.

EDF1 accelerates ganglioside GD3 accumulation to boost CD52-mediated CD8+ T cell dysfunction in neuroblastoma

BackgroundHeterogeneous clinical features and prognosis in neuroblastoma (NB) children are frequently dominated by immune elements. Dysfunction and apoptosis in immune cells result from the exposure to continuous tumor-related antigen stimulation and coinhibitory signals. To date, key factors pointing to the restriction of NB-specific CD8+ T cells remain elusive.MethodsWe performed bulk-RNA sequencing and lipidomic analyses of children with mediastinal NB. Bioinformatics analysis and biological validation were applied to uncover the underlying mechanism.ResultsThree subtypes were identified using nonnegative matrix factorization (NMF), among which we highlighted an apoptotic status of infiltrated CD8+ T cells, along with the highest CD52 and EDF1 expression in Cluster3 (C3) subtypes. It was verified that high EDF1 expression in NB cells led to Lactosylceramide (LacCer) accumulation, as well as downstream ganglioside-GD3, which subsequently increased the expression of CD52 and immune checkpoint genes, chemotaxis, and apoptosis-related events in activated CD8+T cells. Mechanistically, EDF1 was recruited as a coactivator to form the NF-κB/RelA/EDF1 complex, which further prevented the promoter region methylation of ST8SIA1, to elevate its transcription.ConclusionThese findings characterize abundant GD3 in NB cells, which regulated by the EDF1/RelA/ST8SIA1 axis, is responsible for CD8+ T cell dysfunction. Inhibition of EDF1 may reduce suppressive factors and prevent immune escape of NB cells. Modulating NB-associated GD3 levels through metabolic intervention is beneficial for tuning the depth and duration of responses to current NB therapies. The integration of transcriptomic and lipidomic data offers a more comprehensive understanding of the interaction between LacCer metabolites and the immune status in NB.Graphical

Cancer cells avoid ferroptosis induced by immune cells via fatty acid binding proteins

BackgroundCancer creates an immunosuppressive environment that hampers immune responses, allowing tumors to grow and resist therapy. One way the immune system fights back is by inducing ferroptosis, a type of cell death, in tumor cells through CD8 + T cells. This involves lipid peroxidation and enzymes like lysophosphatidylcholine acyltransferase 3 (Lpcat3), which makes cells more prone to ferroptosis. However, the mechanisms by which cancer cells avoid immunotherapy-mediated ferroptosis are unclear. Our study reveals how cancer cells evade ferroptosis and anti-tumor immunity through the upregulation of fatty acid-binding protein 7 (Fabp7).MethodsTo explore how cancer cells resist immune cell-mediated ferroptosis, we used a comprehensive range of techniques. We worked with cell lines including PD1-sensitive, PD1-resistant, B16F10, and QPP7 glioblastoma cells, and conducted in vivo studies in syngeneic 129 Sv/Ev, C57BL/6, and conditional knockout mice with Rora deletion specifically in CD8+ T cells, Cd8 cre;Rorafl mice. Methods included mass spectrometry-based lipidomics, targeted lipidomics, Oil Red O staining, Seahorse analysis, quantitative PCR, immunohistochemistry, PPARγ transcription factor assays, ChIP-seq, untargeted lipidomic analysis, ROS assay, ex vivo co-culture of CD8+ T cells with cancer cells, ATAC-seq, RNA-seq, Western blotting, co-immunoprecipitation assay, flow cytometry and Imaging Mass Cytometry.ResultsPD1-resistant tumors upregulate Fabp7, driving protective metabolic changes that shield cells from ferroptosis and evade anti-tumor immunity. Fabp7 decreases the transcription of ferroptosis-inducing genes like Lpcat3 and increases the transcription of ferroptosis-protective genes such as Bmal1 through epigenetic reprogramming. Lipidomic profiling revealed that Fabp7 increases triglycerides and monounsaturated fatty acids (MUFAs), which impede lipid peroxidation and ROS generation. Fabp7 also improves mitochondrial function and fatty acid oxidation (FAO), enhancing cancer cell survival. Furthermore, cancer cells increase Fabp7 expression in CD8+ T cells, disrupting circadian clock gene expression and triggering apoptosis through p53 stabilization. Clinical trial data revealed that higher FABP7 expression correlates with poorer overall survival and progression-free survival in patients undergoing immunotherapy.ConclusionsOur study uncovers a novel mechanism by which cancer cells evade immune-mediated ferroptosis through Fabp7 upregulation. This protein reprograms lipid metabolism and disrupts circadian regulation in immune cells, promoting tumor survival and resistance to immunotherapy. Targeting Fabp7 could enhance immunotherapy effectiveness by re-sensitizing resistant tumors to ferroptosis.

Reshaping lipid metabolism with long-term alternate day feeding in type 2 diabetes mice

Strategies to improve metabolic health include calorie restriction, time restricted eating and fasting several days per week or month. These approaches have demonstrated benefits for individuals experiencing obesity, metabolic syndrome, and prediabetes. However, their impact on established diabetes remains incompletely studied. The chronicity of type 2 diabetes (T2D) requires that interventions must be undertaken for extended periods of time, typically the entire lifetime of the individual. In this study, we examined the impact of intermittent fasting (IF), with an every-other-day protocol for a duration of 6 months in a murine model of T2D, the db/db (D) mouse on metabolism and liver steatosis. We compared D-IF mice with diabetic ad-libitum (AL; D-AL), control-IF (C-IF) and control-AL (C-AL) cohorts. We demonstrated using lipidomic, microbiome, metabolomic and liver transcriptomic studies that chronic IF improved carbohydrate utilization and glucose homeostasis without weight loss and reduced white adipose tissue inflammation and significantly impacted lipid metabolism in the liver. Microbiome studies and predicted functional analysis of gut microbiota showed that IF increased beneficial bacteria involved in sphingolipid (SL) metabolism. The metabolomic studies showed that oxidation of lipid species and ceramide levels were reduced in D-IF compared to D-AL. The liver lipidomic analysis and liver microarray confirmed a reduction in overall lipid content in D-IF mice compared to D-AL mice, especially in the feeding state as well as an overall reduction in oxidized lipids and ceramides. These studies support that long-term IF can improve glucose homeostasis and dramatically altered lipid metabolism in the absence of weight loss.

Applying newly suggested simultaneous analysis of metabolomics and lipidomics into perfluorooctanesulfonate-derived neurotoxicity mechanism in zebrafish embryos

Developing methodologies for performing multi-omics with one sample has been challenging in zebrafish toxicology; however, related studies are lacking. A new strategy for the simultaneous analysis of metabolomics and lipidomics in zebrafish embryos was proposed and applied to explore the neurotoxicity mechanisms of perfluorooctanesulfonate (PFOS). Metabolite and lipid profiled simultaneously with methyl tert-butyl ether (MTBE) were compared with individual results from other extraction solvents. Behavioral alterations were measured after the zebrafish embryos were exposed to 0.1–20 μM PFOS for 5 days. The metabolite-lipid profiles of the MTBE-based strategy analyzed with optimized larval pooling size of 30 were comparable to those of other extraction solvents, indicating the feasibility and efficiency of MTBE-based multi-omics analysis. Many metabolites and lipids, which were enriched more than those previously reported, completed the toxicity pathways involved in energy metabolism and sphingolipids, improving our understanding of PFOS-induced neurotoxicity mechanism manifested by increased movement under dark conditions. Our novel MTBE-based strategy enabled the multi-omics analysis of one sample with minimal use of zebrafish embryos, thereby improving data reliability on changes in multi-layered biomolecules. This study will advance multi-omics technologies that are critical to elucidating the toxicity mechanisms of toxic chemicals including per- and polyfluoroalkyl substances.

Effect of sous-vide processing duration on flavor and taste variations of oyster (Crassostrea gigas).

Sous-vide (SV), as a mild processing technique, exhibits some potential for keeping the original flavor of oyster. The dynamic changes mechanism of flavor and taste in oyster during SV processing (0-30min/75°C) were investigated. SV processing for 10-15min improved the umami of oysters, likely due to the increase in adenosine monophosphate and glutamate, while processing for 20-30min resulted in a significant loss of "grassy" flavor. GC-MS and GC-IMS analysis showed that the loss of short-chain aldehydes, such as (E)-2-pentenal, (E)-2-hexenal and (E, E)-2,4-hexadienal may be related to the weakening of the "grassy" flavor, and the formation of 2,3-diethylpyrazine and octanal produced a "cooked" and "fatty" flavor. The analysis of lipidomics indicated that phosphatidylethanolamine, lysophosphatidylcholine and sphingomyelin, synthesized mainly through glycerophospholipid and sphingolipid metabolism, were key precursors for aldehyde formation. This study provides a theoretical basis for controlling the flavor quality of oyster during mild processing.

Effect of storage temperature on the quality of brown rice revealed by integrated GC-MS and lipidomics analysis.

Brown rice is highly nutritious but more susceptible to deterioration without the rice husk's protection. In this study, the mechanism of storage temperature on brown rice quality was investigated based on GC-MS and lipidomics. The results showed that both 15°C and 20°C storage retarded the lipids oxidation of brown rice and maintained its texture properties. Moreover, 1-octanol, 1-octen-3-ol, octanal, fitone, 2, 3-dihydrobenzofuran, dodecane, and tridecane were key biomarkers in cooked brown rice flavor. Furthermore, significant correlations between lipid oxidation, texture, and flavor biomarkers were revealed. Notably, the quality of brown rice stored at 15°C (Fatty acid value=23.0mg/100g) was superior to that at 20°C (Fatty acid value=24.3mg/100g) due to more effective retardation of glycerophospholipid, glycerolipid, and phospholipid metabolism. This work provided a better understanding of temperature-controlled storage of brown rice and give recommendation for potential commercial applications.

Widely targeted plasma lipidomic analysis of Term Low Birth Weight Infants: unraveling signatures and implications for early growth patterns

Widely targeted plasma lipidomic analysis of Term Low Birth Weight Infants: unraveling signatures and implications for early growth patterns

Assessment of the effects of cadmium, samarium and gadolinium on the blue mussel (Mytilus edulis): A biochemical, transcriptomic and metabolomic approach.

Improving the understanding of how chemicals affect on organisms and assessing the associated environmental risks is of major interest in environmental studies. This can be achieved by using complementary approaches based on the study of the molecular responses of organisms. Because of the known chemical pressures on the environment, regulations on the content of some chemicals, such as cadmium, have been mostly completed. In contrast, the environmental toxicity of rare earth elements (REEs), which are widely used in industry, has only recently begun to receive attention. Here, we investigated the effects of cadmium, and two REEs, samarium and gadolinium, on marine mussels under laboratory exposures. We found that after an 8-day exposure at 500 µg/L, the metals were bioaccumulated by the mussels. Furthermore, samarium and gadolinium affected two oxidative stress biomarkers, GST and SOD. Lipidomic analysis showed that lipid content was modulated by the REEs, but not by cadmium. Interestingly, several compounds belonging to the phosphoinositide metabolism were more abundant, suggesting a pro-mitotic or cell survival response, while a higher abundance of cardiolipins after samarium exposure suggested an alteration of mitochondrial activity. Moreover, depending on the tissue and the metal considered, transcriptional analyses revealed an effect on metallothionein, hsp70/90, energy metabolism enzymes, as well as pro-mitotic transcript accumulation. Thus, this study sheds a new light on metal toxicity and in particularl REEs by highlighting the accumulation and toxicity of cadmium, samarium and gadolinium at 500 µg/L at different molecular levels, from gene expression to the lipidome of blue mussels.

Multi-omics dissection of metabolic dysregulation associated with immune recovery in people living with HIV-1

BackgroundDespite the success of antiretroviral therapy (ART) in suppressing HIV-1 replication, some people living with HIV-1 (PLWH) fail to achieve an optimal recovery of CD4 T cells, and precise metabolic regulation underlying immune recovery remained poorly understood.MethodsIn this cross-sectional study, mass spectrometry was used for quantitative analysis of plasma metabolome and lipidome in 24 treatment-naïve PLWH (TNs), 33 immunological responders (IRs), 35 immunological non-responders (INRs), and 16 healthy controls (HCs). The data were analyzed using the Mann–Whitney U-test, Kruskal–Wallis test, Spearman correlation, and LASSO regression analysis.ResultsSignificant metabolic dysregulation was observed in TNs, IRs and INRs compared to HCs. In TNs, metabolomic analysis revealed increased levels of 3-hydroxyoctanoic acid, 3-oxododecanoic acid, 5-hydroxy-L-tryptophan, 5-hydroxyindoleacetic acid, L-kynurenine, oleoylcarnitine, and pseudouridine that were positively correlated with CD8 T cell activation and inflammation-related markers, and decreased levels of phosphorylcholine, ribothymidine, and thymine that were negatively correlated. Notably, 3-hydroxyoctanoic acid and thymine were consistently associated with CD4 T cell counts and inflammation-related markers in PLWH, regardless of ART. Pathway analysis uncovered the biosynthesis of unsaturated fatty acids as the major dysregulated pathway in TNs, IRs, and INRs, while primary bile acid biosynthesis was the dysregulated pathway specifically in INRs. Lipidomic analysis indicated higher plasma triacylglycerols, free fatty acids, ceramide, and monosialodihexosyl gangliosides (GM3) in TNs, IRs, and INRs compared to HCs. Pathway enrichment and differential correlation analyses underscore perturbed systemic lipid metabolism in treatment response to ART, possibly mediated by host-commensal metabolic interactions. Ultimately, we identified two panels, one consisting of 9 metabolites and another of 8 lipids, that can effectively distinguish INRs from IRs.ConclusionsMetabolic aberrations induced by chronic HIV-1 infection persist and do not recover with ART. Abnormal primary bile acid biosynthesis pathway and levels of DHA-containing lipids are closely associated with CD4 T cell recovery. These finding provide new intervention targets to achieve better immune recovery in PLWH.

Lysophosphatidylcholine-Induced Aberrant Adipogenesis in Mesenchymal Stem Cells and Impaired Antibacterial Function in Adipocytes of Creeping Fat.

Creeping fat (CF) in Crohn's disease (CD) is characterized by hyperplastic mesenteric adipose tissue (MAT) encasing fibrotic intestinal segments. CF exhibits disruptions in microbiota and lipid metabolism, particularly in lysophospholipids (LPC). This study aims to elucidate the impact of LPC on adipogenic differentiation of mesenchymal stem cells in CF and its effects on immune defense functions in the differentiated adipocytes. Isolated adipocytes of MAT from CD and Non-CD patients were analyzed for bacterial counts and composition using AQ-PCR and 16S rRNA. RNA sequencing was performed on isolated adipocytes to assess functionality. LPC levels in CD patients and their effects on adipocyte immune defense were measured using lipidomics, ELISA, and bacterial killing assays. A TNBS-induced colitis model was used to measure LPC levels in plasma and gene expression in MAT. Significant shifts in microbial diversity and bacterial load were observed in CF-derived adipocytes, characterized by increased colonization by pathogenic bacteria and diminished antibacterial capabilities. Sequencing analysis revealed downregulation of antimicrobial genes, including SAA1/2, and upregulation of lipid metabolism-related genes. Lipidomic analysis of CF showed elevated LPC levels, a pro-inflammatory lipid also found in plasma of CD patients. In vitro experiments demonstrated LPC promotes adipogenesis through EGR2, while impairing adipocytes' antibacterial immunity. These findings were consistent in the TNBS-treated mouse model, where increased LPC levels in the blood, and a significant reduction in SAA1/2-positive adipocytes were noted. LPC-induced aberrant adipogenesis in CF is a newly identified pathological feature in CD patients and a potential therapeutic target.

Hepatic lipidomics reveal shifts in glycerolipid, phospholipid, and sphingolipid composition associated with hepatic fat accumulation in central bearded dragons (Pogona vitticeps).

To characterize changes in the hepatic lipid profile and metabolic pathways associated with increasing hepatic fat accumulation in bearded dragons (Pogona vitticeps). Untargeted lipidomic analysis was conducted using LC-MS-MS on liver samples from bearded dragons with varying hepatic fat content. Hepatic fat percentage was calculated from digital image analysis of scanned histopathology slides. After data normalization, associations between lipids and hepatic fat percentages were assessed using serial linear models adjusted for false discovery rate, volcano plots, and principal component analysis. Changes in fatty acyl chains of triacylglycerols and phospholipids were characterized graphically using bubble plots. Enrichment and pathway analyses were also performed to examine potential disruptions in lipid metabolic pathways. 36 central bearded dragons were sampled, and 976 lipid molecules were identified and quantified. Triacylglycerols were the most abundant and exhibited significant increases in concentrations and changes in fatty acyl chain characteristics with higher hepatic fat content. Notably, ether-linked glycerolipids were significantly enriched with increasing fat content. Phospholipids, especially phosphatidylethanolamines and phosphatidylinositols, demonstrated a negative association with hepatic fat accumulation, but fatty acyl chains remained stable. Sphingomyelins were also decreased with increasing hepatic fat. This study shows some significant shifts in the hepatic lipidome of bearded dragons with increased hepatic fat, mainly involving glycerolipids, phospholipids, and sphingolipids. These findings reveal both shared and unique features when compared to mammalian and avian fatty liver disease and suggest species-specific lipid adaptive mechanisms.

Apolipoprotein B100 acts as a tumor suppressor in ovarian cancer via lipid/ER stress axis-induced blockade of autophagy.

Ovarian cancer presents a significant treatment challenge due to its insidious nature and high malignancy. As autophagy is a vital cellular process for maintaining homeostasis, targeting the autophagic pathway has emerged as an avenue for cancer therapy. In the present study, we identify apolipoprotein B100 (ApoB100), a key modulator of lipid metabolism, as a potential prognostic biomarker of ovarian cancer. ApoB100 functioned as a tumor suppressor in ovarian cancer, and the knockdown of ApoB100 promoted ovarian cancer progression in vivo. Moreover, ApoB100 blocked autophagic flux, which was dependent on interfering with the lipid accumulation/endoplasmic reticulum (ER) stress axis. The effects of LFG-500, a novel synthetic flavonoid, on ApoB100 induction were confirmed using proteomics and lipidomics analyses. Herein, LFG-500 induced lipid accumulation and ER stress and subsequently blocked autophagy by upregulating ApoB100. Moreover, data from in vivo experiments further demonstrated that ApoB100, as well as the induction of the lipid/ER stress axis and subsequent blockade of autophagy, were responsible for the anti-tumor effects of LFG-500 on ovarian cancer. Hence, our findings support that ApoB100 is a feasible target of ovarian cancer associated with lipid-regulated autophagy and provide evidence for using LFG-500 for ovarian cancer treatment.

Pivotal roles of Plasmodium falciparum lysophospholipid acyltransferase 1 in cell cycle progression and cytostome internalization

The rapid intraerythrocytic replication of Plasmodium falciparum, a deadly species of malaria parasite, requires a quick but constant supply of phospholipids to support marked cell membrane expansion. In the malarial parasite, many enzymes functioning in phospholipid synthesis pathway have not been identified or characterized. Here, we identify P. falciparum lysophospholipid acyltransferase 1 (PfLPLAT1) and show that PfLPLAT1 is vital for asexual parasite cell cycle progression and cytostome internalization. Deficiency in PfLPLAT1 results in decreased parasitemia and prevents transition to the schizont stage. Parasites lacking PfLPLAT1 also exhibit distinctive omega-shaped vacuoles, indicating disrupted cytostome function. Transcriptomic analyses suggest that this deficiency impacts DNA replication and cell cycle regulation. Mass spectrometry-based enzyme assay and lipidomic analysis demonstrate that recombinant PfLPLAT1 exhibits lysophospholipid acyltransferase activity with a preference for unsaturated fatty acids as its acyl donors and lysophosphatidic acids as an acceptor, with its conditional knockout leading to abnormal lipid composition and marked morphological and developmental changes including stage arrest. These findings highlight PfLPLAT1 as a potential target for antimalarial therapy, particularly due to its unique role and divergence from human orthologs.

Lipidomics Reveals Dietary Alpha Linolenic Acid Facilitates Metabolism Related to Division of Labor in Honeybee Workers

The division of labor among honeybee workers contributes to efficient pollination activities. Lipids play a crucial role in behavioral regulation, with pollen serving as a primary source of these lipids. However, the regulatory effect of pollen lipids on the division of labor of honeybee workers remains to be studied. In this study, an in-depth lipidomic analysis based on HPLC-QTOF-MS and UPLC-IM-QTOF-MS was applied. We conducted the first comprehensive lipidomic profiling of the abdomen, brain, and intestine of emerging, nursing, and foraging bees, as well as pollen, thereby establishing a lipid library comprising 646 lipid species. The lipid composition of pollen was found to exhibit characteristics similar to those of honeybee workers, with alpha linolenic acid (ALA) validated as a key labor characteristic lipid. Moderate dietary ALA supplementation reshaped lipid levels and facilitated metabolism related to the labor of division. These findings advance the field of lipidomic analysis in honeybee workers, revealing a novel behavioral regulator and extending the understanding of the nutritional regulation of ALA in the division of labor among honeybee workers.

Lipidomics Analysis Reveals the Effects of Docosahexaenoic Acid from Different Sources on Prefrontal-Cortex Synaptic Plasticity

Background: Docosahexaenoic Acid (DHA) is an extensively used nutrition supplement in dairy food because of its beneficial effects on cognition. To find an effective DHA intervention for the synapses in the cortex during this period, this study aimed to use targeted lipidomics to evaluate the lipid composition of prefrontal-cortex (PFC) tissue in different DHA interference methods. Methods: Analyzed samples were taken from interfering feeding Bama pigs (BPs) (3 months) fed with soybean oil (Group B), blended oil (Group M), naturally DHA-supplemented milk with blended oil (Group OM), and DHA from fish oil (FO) with blended oil (Group Y). We also examined the protein expression levels of BDNF, GAP43, and MBP. Results: The lipidomics analysis identified 80 different related negative-ion lipid content and filtered the biomarker lipids in PFC tissue. We observed significant lipid composition changes between group Y and other groups, especially for content levels of phosphatidylcholine (PC), phosphatidylethanolamine (PE), phosphatidylinositol (PI), phosphatidylserine (PS), and sphingomyelin (SM). The same observations were made from mRNA and protein expressions related to lipid transportation, phosphatidylserine (PS) synthetase, and synaptic plasticity in PFC tissues between group Y and other groups, including the mRNA expression levels of CD36, BDNF, and PTDSS1. The analysis of protein expression levels showed that the metabolism mode of DHA intervention from FO benefited the PFC, PS metabolism, and PFC synaptic plasticity of infants. Conclusions: The results highlight further prospects for the DHA intervention mode, which provides new routes for other studies on polyunsaturated-fatty-acid (PUFA) interference for infants.

The developmental lipidome of Nippostrongylus brasiliensis

BackgroundNippostrongylus brasiliensis—a nematode of rodents—is commonly used as a model to study the immunobiology of parasitic nematodes. It is a member of the Strongylida—a large order of socioeconomically important parasitic nematodes of animals. Lipids are known to play essential roles in nematode biology, influencing cellular membranes, energy storage and/or signalling.MethodsThe present investigation provides a comprehensive, untargeted lipidomic analysis of four developmental stages/sexes (i.e. egg, L3, adult female and adult male stages) of N. brasiliensis utilising liquid chromatography coupled to mass spectrometry.ResultsWe identified 464 lipid species representing 18 lipid classes and revealed distinct stage-specific changes in lipid composition throughout nematode development. Triacylglycerols (TGs) dominated the lipid profile in the egg stage, suggesting a key role for them in energy storage at this early developmental stage. As N. brasiliensis develops, there was a conspicuous transition toward membrane-associated lipids, including glycerophospholipids (e.g. PE and PC) and ether-linked lipids, particularly in adult stages, indicating a shift toward host adaptation and membrane stabilisation.ConclusionsWe provide a comprehensive insight into the lipid composition and abundance of key free-living and parasitic stages of N. brasiliensis. This study provides lipidomic resources to underpin the detailed exploration of lipid biology in this model parasitic nematode.Graphical

Lipidomic Expression Analysis In Carotid Atherosclerotic Disease: A Systematic Review.

Lipids are key molecules for atherosclerosis, with tight regulation mechanisms, making them potential biomarkers for disease-specific diagnostics and therapeutics. Therefore, we aim to perform a systematic literature review on lipidomic analysis in serum/plasma and plaque samples of patients with carotid atherosclerosis. We performed a systematic review following the PRISMA guidelines on the lipidomic profile in serum/plasma and carotid artery plaques from patients with significant carotid disease by degree of stenosis in preoperative imaging and clinical presentation (symptomatic, asymptomatic, radiation-induced carotid disease). Main outcome was the differential lipidomic expression of serum/plasma, and plaque lipids of patients with carotid artery atherosclerosis. Studies were screened using the Newcastle-Ottawa Scale to determine the quality of the design and content of the selected manuscripts. We included fourteen studies, from which ten included plaque analysis. The lipidomic analysis revealed that sterols and hydroxycholesterols were consistently found in both blood and plaque across studies. Triacylglycerols were present in both sample types, with specific forms linked to radiation-induced carotid artery disease. Symptomatic patients exhibited esterified hydroxyeicosatetraenoic acids and arachidonic acid precursors exclusively in plaque with an inflammatory profile of the disease. In contrast, docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) were associated with plaque stability. Diabetics showed nonesterified fatty acids and specific phospholipids only in plaque, indicating localized lipid changes. Other pathways relevant to disease progression include the sphingolipids and ceramide pathways with inflammatory profiling. Lipidomic provides an innovative approach to stratify carotid atherosclerotic disease. Integrating lipidomic data with other -omics approaches may further enhance our understanding of disease mechanisms and aid in the development of precision medicine approaches, specifically in those patients at risk for early carotid atherosclerotic disease.

Inflammatory disease progression shapes nanoparticle biomolecular corona-mediated immune activation profiles

Polymeric nanoparticles (NPs) are promising tools used for immunomodulation and drug delivery in various disease contexts. The interaction between NP surfaces and plasma-resident biomolecules results in the formation of a biomolecular corona, which varies patient-to-patient and as a function of disease state. This study investigates how the progression of acute systemic inflammatory disease influences NP corona compositions and the corresponding effects on innate immune cell interactions, phenotypes, and cytokine responses. NP coronas alter cell associations in a disease-dependent manner, induce differential co-stimulatory and co-inhibitory molecule expression, and influence cytokine release. Integrated multi-omics analysis of proteomics, lipidomics, metabolomics, and cytokine datasets highlight a set of differentially enriched TLR4 ligands that correlate with dynamic NP corona-mediated immune activation. Pharmacological inhibition and genetic knockout studies validate that NP coronas mediate this response through TLR4/MyD88/NF-κB signaling. Our findings illuminate the personalized nature of corona formation under a dynamic inflammatory condition and its impact on NP-mediated immune activation profiles and inflammation, suggesting that disease progression-related alterations in plasma composition can manifest in the corona to cause unintended toxicity and altered therapeutic efficacy.