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Oxylipins are active lipid compounds formed through the oxidation of unsaturated fatty acids. These compounds have drawn considerable attention due to the potential impact on human health and processed food quality. Therefore, this study aimed to deepen current understanding and assess recent analytical advancements regarding the physiological roles of oxylipins in processed food products using lipidomics. The mechanisms behind oxylipins production in processed foods were extensively investigated, underscoring potential associations with chronic diseases. This indicates the need for innovative strategies to mitigate harmful oxylipins levels to enhance the safety and shelf life of processed food products. The results showed that mitigation methods, including the use of antioxidants and optimization of processing parameters, reduced oxylipins levels. The integration of lipidomics with food safety and quality control processes is evident in cutting-edge methods such as nuclear magnetic resonance and mass spectrometry for compliance and real-time evaluation. Aside from envisioning the future trajectory of food science and industry through prospective studies on oxylipins and processed foods, the results also provide the basis for future investigations, innovation, and advancements in the dynamic field of food science and technology.

Hypertriglyceridemia is a risk factor for type 2 diabetes and cardiovascular disease (CVD). Plasma triglycerides (TGs) are a key factor for assessing the risk of diabetes or CVD. However, previous lipidomics studies have demonstrated that not all TG molecules behave the same way. Individual TGs with different fatty acid compositions are regulated differentially under various conditions. In addition, distinct groups of TGs were identified to be associated with increased diabetes risk (TGs with lower carbon number [C#] and double-bond number [DB#]), or with decreased risk (TGs with higher C# and DB#). In this study, we examined the effects of high-fat feeding in rats on plasma lipid profiles with special attention to TG profiles. Wistar rats were maintained on either a low-fat (control) or high-fat diet (HFD) for 2 weeks. Plasma samples were obtained before and 2.5 h after a meal (n = 10 each) and subjected to lipidomics analyses. High-fat feeding significantly impacted circulating lipid profiles, with the most significant effects observed on TG profile. The effects of an HFD on individual TG species depended on DB# in their fatty acid chains; an HFD increased TGs with low DB#, associated with increased diabetes risk, but decreased TGs with high DB#, associated with decreased risk. These changes in TGs with an HFD were associated with decreased indices of hepatic stearoyl-CoA desaturase (SCD) activity, assessed from hepatic fatty acid profiles. Decreased SCD activity would reduce the conversion of saturated to monounsaturated fatty acids, contributing to the increases in saturated TGs or TGs with low DB#. In addition, an HFD selectively depleted ω-3 polyunsaturated fatty acids (PUFAs), contributing to the decreases in TGs with high DB#. Thus, an HFD had profound impacts on circulating TG profiles. Some of these changes were at least partly explained by decreased hepatic SCD activity and depleted ω-3 PUFA.

Cardiolipin (CL) is a unique, four-chain phospholipid synthesized in the inner mitochondrial membrane (IMM). The acyl chain composition of CL is regulated through a remodeling pathway, whose loss causes mitochondrial dysfunction in Barth syndrome (BTHS). Yeast has been used extensively as a model system to characterize CL metabolism, but mutants lacking its two remodeling enzymes, Cld1p and Taz1p, exhibit mild structural and respiratory phenotypes compared to mammalian cells. Here, we show an essential role for CL remodeling in the structure and function of the IMM in yeast grown under reduced oxygenation. Microaerobic fermentation, which mimics natural yeast environments, caused the accumulation of saturated fatty acids and, under these conditions, remodeling mutants showed a loss of IMM ultrastructure. We extended this observation to HEK293 cells, where phospholipase A2 inhibition by Bromoenol lactone resulted in respiratory dysfunction and cristae loss upon mild treatment with exogenous saturated fatty acids. In microaerobic yeast, remodeling mutants accumulated unremodeled, saturated CL, but also displayed reduced total CL levels, highlighting the interplay between saturation and CL biosynthesis and/or breakdown. We identified the mitochondrial phospholipase A1 Ddl1p as a regulator of CL levels, and those of its precursors phosphatidylglycerol and phosphatidic acid, under these conditions. Loss of Ddl1p partially rescued IMM structure in cells unable to initiate CL remodeling and had differing lipidomic effects depending on oxygenation. These results introduce a revised yeast model for investigating CL remodeling and suggest that its structural functions are dependent on the overall lipid environment in the mitochondrion.

Posttraumatic stress disorder (PTSD) can develop after trauma exposure. Some studies report that women develop PTSD at twice the rate of men, despite greater trauma exposure in men. Lipids and their metabolites (lipidome) regulate a myriad of key biological processes and pathways such as membrane integrity, oxidative stress, and neuroinflammation in the brain by maintaining neuronal connectivity and homeostasis. In this study, we analyzed the lipidome of 40 adults with PTSD and 40 trauma-exposed non-PTSD individuals (n = 20/sex/condition; 19-39 years old). Plasma samples were analyzed for lipidomics using Quadrupole Time-of-Flight (QToF) mass spectrometry. Additionally, ~ 90 measures were collected, on sleep, and mental and physical health indices. Poorer sleep quality was associated with greater PTSD severity in both sexes. The lipidomics analysis identified a total of 348 quantifiable known lipid metabolites and 1951 lipid metabolites that are yet unknown; known metabolites were part of 13 lipid subclasses. After adjusting for BMI and sleep quality, in women with PTSD, only one lipid subclass, phosphatidylethanolamine (PE) was altered, whereas, in men with PTSD, 9 out of 13 subclasses were altered compared to non-PTSD women and men, respectively. Severe PTSD was associated with 22% and 5% of altered lipid metabolites in men and women, respectively. Of the changed metabolites, only 0.5% measures (2 PEs and cholesterol) were common between women and men with PTSD. Several sphingomyelins, PEs, ceramides, and triglycerides were increased in men with severe PTSD. The correlations between triglycerides and ceramide metabolites with cholesterol metabolites and systolic blood pressure were dependent upon sex and PTSD status. Alterations in triglycerides and ceramides are linked with cardiac health and metabolic function in humans. Thus, disturbed sleep and higher body mass may have contributed to changes in the lipidome found in PTSD.

Phospholipase A2 (PLA2) constitutes a superfamily of enzymes that hydrolyze phospholipids at their sn-2 fatty acyl position. Our laboratory has demonstrated that PLA2 enzymes regulate membrane remodeling and cell signaling by their specificity toward their phospholipid substrates at the molecular level. Recent in vitro studies show that each type of PLA2, including Group IVA cytosolic PLA2 (cPLA2), Group V secreted PLA2 (sPLA2), Group VIA calcium independent PLA2 (iPLA2) and Group VIIA lipoprotein-associated PLA2, also known as platelet-activating factor acetyl hydrolase, can discriminate exquisitely between fatty acids at the sn-2 position. Thus, these enzymes regulate the production of diverse PUFA precursors of inflammatory metabolites. We now determined PLA2 specificity in macrophage cells grown in cell culture, where the amounts and localization of the phospholipid substrates play a role in which specific phospholipids are hydrolyzed by each enzyme type. We used PLA2 stereospecific inhibitors in tandem with a novel UPLC-MS/MS-based lipidomics platform to quantify more than a thousand unique phospholipid molecular species demonstrating cPLA2, sPLA2, and iPLA2 activity and specificity toward the phospholipids in living cells. The observed specificity follows the in vitro capability of the enzymes and can reflect the enrichment of certain phospholipid species in specific membrane locations where particular PLA2s associate. For assaying, we target 20:4-PI for cPLA2, 22:6-PG for sPLA2, and 18:2-PC for iPLA2. These new results provide great insight into the physiological role of PLA2 enzymes in cell membrane remodeling and could shed light on how PLA2 enzymes underpin inflammation and other lipid-related diseases.

BACKGROUND: The oleaginous yeast Rhodotorula toruloides is a promising chassis organism for the biomanufacturing of value-added bioproducts. It can accumulate lipids at a high fraction of biomass. However, metabolic engineering efforts in this organism have progressed at a slower pace than those in more extensively studied yeasts. Few studies have investigated the lipid accumulation phenotype exhibited by R. toruloides under nitrogen limitation conditions. Consequently, there have been only a few studies exploiting the lipid metabolism for higher product titers. RESULTS: We performed a multi-omic investigation of the lipid accumulation phenotype under nitrogen limitation. Specifically, we performed comparative transcriptomic and lipidomic analysis of the oleaginous yeast under nitrogen-sufficient and nitrogen deficient conditions. Clustering analysis of transcriptomic data was used to identify the growth phase where nitrogen-deficient cultures diverged from the baseline conditions. Independently, lipidomic data was used to identify that lipid fractions shifted from mostly phospholipids to mostly storage lipids under the nitrogen-deficient phenotype. Through an integrative lens of transcriptomic and lipidomic analysis, we discovered that R. toruloides undergoes lipid remodeling during nitrogen limitation, wherein the pool of phospholipids gets remodeled to mostly storage lipids. We identify specific mRNAs and pathways that are strongly correlated with an increase in lipid levels, thus identifying putative targets for engineering greater lipid accumulation in R. toruloides. One surprising pathway identified was related to inositol phosphate metabolism, suggesting further inquiry into its role in lipid accumulation. CONCLUSIONS: Integrative analysis identified the specific biosynthetic pathways that are differentially regulated during lipid remodeling. This insight into the mechanisms of lipid accumulation can lead to the success of future metabolic engineering strategies for overproduction of oleochemicals.

Regular exercise promotes whole-body health and prevents disease, but the underlying molecular mechanisms are incompletely understood1-3. Here, the Molecular Transducers of Physical Activity Consortium4 profiled the temporal transcriptome, proteome, metabolome, lipidome, phosphoproteome, acetylproteome, ubiquitylproteome, epigenome and immunome in whole blood, plasma and 18 solid tissues in male and female Rattus norvegicus over eight weeks of endurance exercise training. The resulting data compendium encompasses 9,466 assays across 19 tissues, 25 molecular platforms and 4 training time points. Thousands of shared and tissue-specific molecular alterations were identified, with sex differences found in multiple tissues. Temporal multi-omic and multi-tissue analyses revealed expansive biological insights into the adaptive responses to endurance training, including widespread regulation of immune, metabolic, stress response and mitochondrial pathways. Many changes were relevant to human health, including non-alcoholic fatty liver disease, inflammatory bowel disease, cardiovascular health and tissue injury and recovery. The data and analyses presented in this study will serve as valuable resources for understanding and exploring the multi-tissue molecular effects of endurance training and are provided in a public repository ( https://motrpac-data.org/ ).

Glioblastoma is the most aggressive primary brain malignancy in adults, and has a survival duration of approximately 15 months. First line treatment involves surgical resection, chemotherapy, and radiation, but despite the multi-pronged approach and advances in cancer research, glioblastoma remains devastating with a high mortality rate. Lipidomics is an emerging discipline that studies lipid pathways and characteristics, and is a promising field to understand biochemical mechanisms. In glioblastoma, disrupted lipid homeostasis has been reported in the literature. A thorough understanding of serum lipidomics may offer ways to better understand glioblastoma biomarkers, prognosis, and treatment options. Here, we review the literature, offering future directions for lipidomics research in glioblastomas.

The purpose of this study was to investigate changes in the lipidome of patients with sepsis to identify signaling lipids associated with poor outcomes that could be linked to future therapies. Adult patients with sepsis were enrolled within 24h of sepsis recognition. Patients meeting Sepsis-3 criteria were enrolled from the emergency department or intensive care unit and blood samples were obtained. Clinical data were collected and outcomes of rapid recovery, chronic critical illness (CCI), or early death were adjudicated by clinicians. Lipidomic analysis was performed on two platforms, the Sciex™ 5500 device to perform a lipidomic screen of 1450 lipid species and a targeted signaling lipid panel using liquid-chromatography tandem mass spectrometry. For the lipidomic screen, there were 274 patients with sepsis: 192 with rapid recovery, 47 with CCI, and 35 with early deaths. CCI and early death patients were grouped together for analysis. Fatty acid (FA) 12:0 was decreased in CCI/early death, whereas FA 17:0 and 20:1 were elevated in CCI/early death, compared to rapid recovery patients. For the signaling lipid panel analysis, there were 262 patients with sepsis: 189 with rapid recovery, 45 with CCI, and 28 with early death. Pro-inflammatory signaling lipids from ω-6 poly-unsaturated fatty acids (PUFAs), including 15-hydroxyeicosatetraenoic (HETE), 12-HETE, and 11-HETE (oxidation products of arachidonic acid [AA]) were elevated in CCI/early death patients compared to rapid recovery. The pro-resolving lipid mediator from ω-3 PUFAs, 14(S)-hydroxy docosahexaenoic acid (14S-HDHA), was also elevated in CCI/early death compared to rapid recovery. Signaling lipids of the AA pathway were elevated in poor-outcome patients with sepsis and may serve as targets for future therapies.

BACKGROUND: Oxidized phospholipids play a key role in the atherogenic potential of lipoprotein(a) (Lp[a]); however, Lp(a) is a complex particle that warrants research into additional proinflammatory mediators. We hypothesized that additional Lp(a)-associated lipids contribute to the atherogenicity of Lp(a). METHODS: Untargeted lipidomics was performed on plasma and isolated lipoprotein fractions. The atherogenicity of the observed Lp(a)-associated lipids was tested ex vivo in primary human monocytes by RNA sequencing, ELISA, Western blot, and transendothelial migratory assays. Using immunofluorescence staining and single-cell RNA sequencing, the phenotype of macrophages was investigated in human atherosclerotic lesions. RESULTS: Compared with healthy individuals with low/normal Lp(a) levels (median, 7 mg/dL [18 nmol/L]; n=13), individuals with elevated Lp(a) levels (median, 87 mg/dL [218 nmol/L]; n=12) demonstrated an increase in lipid species, particularly diacylglycerols (DGs) and lysophosphatidic acid (LPA). DG and the LPA precursor lysophosphatidylcholine were enriched in the Lp(a) fraction. Ex vivo stimulation with DG(40:6) demonstrated a significant upregulation in proinflammatory pathways related to leukocyte migration, chemotaxis, NF-κB (nuclear factor kappa B) signaling, and cytokine production. Functional assessment showed a dose-dependent increase in the secretion of IL (interleukin)-6, IL-8, and IL-1β after DG(40:6) and DG(38:4) stimulation, which was, in part, mediated via the NLRP3 (NOD [nucleotide-binding oligomerization domain]-like receptor family pyrin domain containing 3) inflammasome. Conversely, LPA-stimulated monocytes did not exhibit an inflammatory phenotype. Furthermore, activation of monocytes by DGs and LPA increased their transendothelial migratory capacity. Human atherosclerotic plaques from patients with high Lp(a) levels demonstrated colocalization of Lp(a) with M1 macrophages, and an enrichment of CD68+IL-18+TLR4+ (toll-like receptor) TREM2+ (triggering receptor expressed on myeloid cells) resident macrophages and CD68+CASP1+ (caspase) IL-1B+SELL+ (selectin L) inflammatory macrophages compared with patients with low Lp(a). Finally, potent Lp(a)-lowering treatment (pelacarsen) resulted in a reduction in specific circulating DG lipid subspecies in patients with cardiovascular disease with elevated Lp(a) levels (median, 82 mg/dL [205 nmol/L]). CONCLUSIONS: Lp(a)-associated DGs and LPA have a potential role in Lp(a)-induced monocyte inflammation by increasing cytokine secretion and monocyte transendothelial migration. This DG-induced inflammation is, in part, NLRP3 inflammasome dependent.

BACKGROUND: Dyslipidemia is an independent risk factor for coronary heart disease (CHD). Standard lipid panel cannot capture the complexity of the blood lipidome (ie, all molecular lipids in the blood). To date, very few large-scale epidemiological studies have assessed the full spectrum of the blood lipidome on risk of CHD, especially in a longitudinal setting. METHODS AND RESULTS: Using an untargeted liquid chromatography-mass spectrometry, we repeatedly measured 1542 lipid species from 1835 unique American Indian participants who attended 2 clinical visits (≈5.5 years apart) and followed up to 17.8 years in the Strong Heart Family Study (SHFS). We first identified baseline lipid species associated with risk of CHD, followed by replication in a European population. The model adjusted for age, sex, body mass index, smoking, hypertension, diabetes, low-density lipoprotein cholesterol, estimated glomerular filtration rate, education, and physical activity at baseline. We then examined the longitudinal association between changes in lipid species and changes in cardiovascular risk factors during follow-up. Multiple testing was controlled by the false discovery rate. We found that baseline levels of multiple lipid species (eg, phosphatidylcholines, phosphatidylethanolamines, and ceramides) were associated with the risk of CHD and improved the prediction accuracy over conventional risk factors in American Indian people. Some identified lipids in American Indian people were replicated in European people. Longitudinal changes in multiple lipid species (eg, acylcarnitines, phosphatidylcholines, and triacylglycerols) were associated with changes in cardiovascular risk factors. CONCLUSIONS: Baseline plasma lipids and their longitudinal changes over time are associated with risk of CHD. These findings provide novel insights into the role of dyslipidemia in CHD.

In pre-disposed individuals, a reprogramming of the hepatic lipid metabolism may support liver cancer initiation. We conducted a high-resolution mass spectrometry based untargeted lipidomics analysis of pre-diagnostic serum samples from a nested case-control study (219 liver cancer cases and 219 controls) within the Alpha-Tocopherol, Beta-Carotene Cancer Prevention (ATBC) Study. Out of 462 annotated lipids, 158 (34.2%) were associated with liver cancer risk in a conditional logistic regression analysis at a false discovery rate (FDR)

Adipose tissue is the site of long-term energy storage. During the fasting state, exercise, and cold exposure, the white adipose tissue mobilizes energy for peripheral tissues through lipolysis. The mobilization of lipids from white adipose tissue to the liver can lead to excess triglyceride accumulation and fatty liver disease. Although the white adipose tissue is known to release free fatty acids, a comprehensive analysis of lipids mobilized from white adipocytes in vivo has not been completed. In these studies, we provide a comprehensive quantitative analysis of the adipocyte-secreted lipidome and show that there is interorgan crosstalk with liver. Our analysis identifies multiple lipid classes released by adipocytes in response to activation of lipolysis. Time-dependent analysis of the serum lipidome showed that free fatty acids increase within 30 min of β3-adrenergic receptor activation and subsequently decrease, followed by a rise in serum triglycerides, liver triglycerides, and several ceramide species. The triglyceride composition of liver is enriched for linoleic acid despite higher concentrations of palmitate in the blood. To further validate that these findings were a specific consequence of lipolysis, we generated mice with conditional deletion of adipose tissue triglyceride lipase exclusively in adipocytes. This loss of in vivo adipocyte lipolysis prevented the rise in serum free fatty acids and hepatic triglycerides. Furthermore, conditioned media from adipocytes promotes lipid remodeling in hepatocytes with concomitant changes in genes/pathways mediating lipid utilization. Together, these data highlight critical role of adipocyte lipolysis in interorgan crosstalk between adipocytes and liver.

Pulmonary alveolar proteinosis (PAP) is a life-threatening, rare lung syndrome for which there is no cure and no approved therapies. PAP is a disease of lipid accumulation characterized by alveolar macrophage foam cell formation. While much is known about the clinical presentation, there is a paucity of information regarding temporal changes in lipids throughout the course of disease. Our objectives were to define the detailed lipid composition of alveolar macrophages in PAP patients at the time of diagnosis and during treatment. We performed comprehensive mass spectrometry to profile the lipid signature of alveolar macrophages obtained from three independent mouse models of PAP and from PAP and non-PAP patients. Additionally, we quantified changes in macrophage-associated lipids during clinical treatment of PAP patients. We found remarkable variations in lipid composition in PAP patients, which were consistent with data from three independent mouse models. Detailed lipidomic analysis revealed that the overall alveolar macrophage lipid burden inversely correlated with clinical improvement and response to therapy in PAP patients. Specifically, as PAP patients experienced clinical improvement, there was a notable decrease in the total lipid content of alveolar macrophages. This crucial observation suggests that the levels of these macrophage-associated lipids can be utilized to assess the efficacy of treatment. These findings provide valuable insights into the dysregulated lipid metabolism associated with PAP, offering the potential for lipid profiling to serve as a means of monitoring therapeutic interventions in PAP patients.

LIPID MAPS (LIPID Metabolites and Pathways Strategy), www.lipidmaps.org, provides a systematic and standardized approach to organizing lipid structural and biochemical data. Founded 20 years ago, the LIPID MAPS nomenclature and classification has become the accepted community standard. LIPID MAPS provides databases for cataloging and identifying lipids at varying levels of characterization in addition to numerous software tools and educational resources, and became an ELIXIR-UK data resource in 2020. This paper describes the expansion of existing databases in LIPID MAPS, including richer metadata with literature provenance, taxonomic data and improved interoperability to facilitate FAIR compliance. A joint project funded by ELIXIR-UK, in collaboration with WikiPathways, curates and hosts pathway data, and annotates lipids in the context of their biochemical pathways. Updated features of the search infrastructure are described along with implementation of programmatic access via API and SPARQL. New lipid-specific databases have been developed and provision of lipidomics tools to the community has been updated. Training and engagement have been expanded with webinars, podcasts and an online training school.

BACKGROUND AND AIMS: Gallstone disease (GSD) associates with significant morbidity and mortality. Decreased secretion of bile acids has been suggested as a driving factor for GSD. Recently, we linked the protein phosphatase 1 regulatory subunit 3 beta (PPP1R3B) rs4240624 genotype to decreased bile acid levels in bile. In this study, we investigated whether these individuals had an increased risk for GSD as well as the differences in the lipid composition of the gallbladder bile of these individuals compared to controls and patients with GSD. METHODS: Bile acids, cholesterol, and phospholipid levels in gallbladder bile samples were enzymatically measured in 46 patients (34 female, age 45.7 ± 9.8 years, BMI 41.3 ± 4.4 kg/m2) who underwent elective laparoscopic Roux-en-Y gastric bypass. The lipidome of gallbladder bile was analyzed using high-performance liquid chromatography-mass spectrometry. Gallstone status was evaluated using abdominal ultrasonography before the surgery. RESULTS: The G allele of PPP1R3B rs4240624 was significantly associated with GSD in patients with obesity. We validated this association in the UK Biobank. Bile lipidomics demonstrated that 13 of the 17 minor lipid classes measured were higher in individuals with the G allele. The concentrations of bile acids, cholesterol, and phospholipids, as well as the cholesterol saturation index, were lower in patients with GSD than in those without gallstones. GSD had an effect similar to that of PPP1R3B genotype on minor lipids. CONCLUSION: The PPP1R3B rs4240624 genotype is associated with gallstones and with changes in gallbladder bile similar to those observed in patients with gallstones, suggesting that the PPP1R3B genotype contributes to the risk of gallstones by altering the bile lipidome.

Oxylipins are a group of bioactive fatty acid metabolites generated via enzymatic oxygenation. They are notably involved in inflammation, pain, vascular tone, hemostasis, thrombosis, immunity, and coagulation. Oxylipins have become the focus of therapeutic intervention since they are implicated in many conditions, such as nonalcoholic fatty liver disease, cardiovascular disease, and aging. The liver plays a crucial role in lipid metabolism and distribution throughout the organism. Long-term exposure to pesticides is suspected to contribute to hepatic carcinogenesis via notable disruption of lipid metabolism. Prometryn is a methylthio-s-triazine herbicide used to control the growth of annual broadleaf and grass weeds in many cultivated plants. The amounts of prometryn documented in the environment, mainly waters, soil and plants used for human and domestic consumption are significantly high. Previous research revealed that prometryn decreased liver development during zebrafish embryogenesis. To understand the mechanisms by which prometryn could induce hepatotoxicity, the effect of prometryn (185 mg/kg every 48 h for seven days) was investigated on hepatic and plasma oxylipin levels in mice. Using an unbiased LC-MS/MS-based lipidomics approach, prometryn was found to alter oxylipins metabolites that are mainly derived from cytochrome P450 (CYP) and lipoxygenase (LOX) in both mice liver and plasma. Lipidomic analysis revealed that the hepatotoxic effects of prometryn are associated with increased epoxide hydrolase (EH) products, increased sEH and mEH enzymatic activities, and induction of oxidative stress. Furthermore, 9-HODE and 13-HODE levels were significantly increased in prometryn treated mice liver, suggesting increased levels of oxidation products. Together, these results support that sEH may be an important component of pesticide-induced liver toxicity.

Mammalian ferredoxin 1 and 2 (FDX1/2) belong to an evolutionary conserved family of iron-sulfur cluster containing proteins and act as electron shutters between ferredoxin reductase (FDXR) and numerous proteins involved in critical biological pathways. FDX1 is involved in biogenesis of steroids and bile acids, Vitamin A/D metabolism, and lipoylation of tricarboxylic acid (TCA) cycle enzymes. FDX1 has been extensively characterized biochemically but its role in physiology and lipid metabolism has not been explored. In this study, we generated Fdx1-deficient mice and showed that knockout of both alleles of the Fdx1 gene led to embryonic lethality. We also showed that like Fdxr+/-+/-, Fdx1+/-+/- had a shorter life span and were prone to steatohepatitis. However, unlike Fdxr+/-+/-, Fdx1+/-+/- were not prone to spontaneous tumors. Additionally, we showed that FDX1 deficiency led to lipid droplet accumulation possibly via the ABCA1-SREBP1/2 pathway. Specifically, untargeted lipidomic analysis showed that FDX1 deficiency led to alterations in several classes of lipids, including cholesterol, triacylglycerides, acylcarnitines, ceramides, phospholipids and lysophospholipids. Taken together, our data indicate that FDX1 is essential for mammalian embryonic development and lipid homeostasis at both cellular and organismal levels.

The yeast vacuole membrane can phase separate into ordered and disordered domains, a phenomenon that is required for micro-lipophagy under nutrient limitation. Despite its importance as a biophysical model and physiological significance, it is not yet resolved if specific lipidome changes drive vacuole phase separation. Here we report that the metabolism of sphingolipids (SLs) and their sorting into the vacuole membrane can control this process. We first developed a vacuole isolation method to identify lipidome changes during the onset of phase separation in early stationary stage cells. We found that early stationary stage vacuoles are defined by an increased abundance of putative raft components, including 40% higher ergosterol content and a nearly 3-fold enrichment in complex SLs (CSLs). These changes were not found in the corresponding whole cell lipidomes, indicating that lipid sorting is associated with domain formation. Several facets of SL composition-headgroup stoichiometry, longer chain lengths, and increased hydroxylations-were also markers of phase-separated vacuole lipidomes. To test SL function in vacuole phase separation, we carried out a systematic genetic dissection of their biosynthetic pathway. The abundance of CSLs controlled the extent of domain formation and associated micro-lipophagy processes, while their headgroup composition altered domain morphology. These results suggest that lipid trafficking can drive membrane phase separation in vivo and identify SLs as key mediators of this process in yeast.

The analysis of gangliosides and glycosphingolipids is crucial for understanding cellular membrane structure and function as well as to accurately diagnose certain inborn errors of metabolism. GM2-gangliosidosis represents a rare and fatal group of lysosomal storage disorders characterized by accumulation of GM2 gangliosides in various tissues and organs. These disorders arise due to deficiency or functional impairment of the β-hexosaminidase A or B enzymes, which are responsible for degradation of GM2 ganglioside. Deficient enzyme activity primarily leads to the accumulation of GM2 gangliosides within the lysosomes of cells. Accurate and rapid diagnostic methods that detect increased levels of GM2 gangliosides in patients with GM2-gangliosidosis can play a significant role in early diagnosis and appropriate treatment of this condition. To address this need, we developed a multiplexed liquid chromatography-tandem mass spectrometry method targeting 84 species of gangliosides and other glycosphingolipids involved in ganglioside metabolism. Reproducibility, linearity, extraction efficiency, and sample stability were evaluated and proof-of-concept data obtained from analysis of serum samples from confirmed cases of GM2-gangliosidosis. This method has the potential to simultaneously monitor the biosynthesis of gangliosides and the lysosomal catabolic pathway serving as a valuable tool for screening and diagnosing an important group of lysosomal storage disorders. [ABSTRACT FROM AUTHOR]

Most melanomas progress from radial to vertical growth phase before spreading locoregionally and distally. Much is still unknown about the metabolic changes in the tumor cells and their microenvironment during this metastatic progression. We aimed to gain new insight into the molecular characteristics of melanoma in regard to spatial lipidomics to deliver new knowledge regarding tumor metastatic progression. We included 10 fresh tumor samples from 10 patients including two in situ melanomas, two invasive primary melanomas, and six metastatic melanomas (four in‐transit metastases and two distant metastases). In addition, we analyzed four healthy skin controls from the same patients. Time‐of‐flight imaging secondary ion mass spectrometry (ToF‐SIMS) enabled detailed spatial‐lipidomics that could be directly correlated with conventional histopathological analysis of consecutive H&E‐stained tissue sections. Significant differences in the lipid profiles were found in primary compared to metastatic melanomas, notably an increase in phosphatidylethanolamine lipids relative to phosphatidylinositol lipids and an increase in GM3 gangliosides in the metastatic samples. Furthermore, analysis of the data from in transit versus distant metastases samples highlighted that specific phospholipids, and a difference in the long versus shorter chain GM3 gangliosides, discriminated the metastatic routes. Further studies are warranted to verify these preliminary findings. Lipidomic changes could serve as a novel biomarker for tumor progression and even serve as a target for novel treatments. Furthermore, analyzing the lipid profiles could help to differentiate between primary and metastatic melanomas in challenging cases. [ABSTRACT FROM AUTHOR]

Background: Overlapping clinical manifestations of irritable bowel syndrome (IBS) and IBS-like symptoms in patients with inflammatory bowel disease (IBD-IBS) present challenges in diagnosis and management. Both conditions are associated with alterations in metabolites, but few studies have described the lipid profiles. Our aim was to pinpoint specific lipids that contribute to the pathogenesis of IBS and IBD-IBS by analyzing multiple biologic samples. Methods: Diarrhea-predominant IBS (IBS-D) patients (n = 39), ulcerative colitis in remission with IBS-like symptoms patients (UCR-IBS) (n = 21), and healthy volunteers (n = 35) were recruited. IBS-D patients meet the Rome IV diagnostic criteria, and UCR-IBS patients matched mayo scores ≤ two points and Rome IV diagnostic criteria. Serum, feces, and mucosa were collected for further analysis. Lipid extraction was carried out by ultra-performance liquid chromatography-high resolution mass spectrometry (UPLC-HRMS). Results: Lipidomics of mucosa and serum samples significantly differed among the three groups. Feces showed the most altered lipid species, and the enrichment analysis of 347 differentially abundant metabolites via KEGG pathway analysis revealed that alpha-linolenic acid metabolism was significantly altered in the two groups (P < 0.01). The ratio of omega-6/omega-3 fatty acid were imbalance in serum samples. Conclusions: This study revealed a comprehensive lipid composition pattern between IBS-D patients and UCR-IBS patients. We found several distinctive lipids involved in alpha-linolenic acid metabolism, reflecting an imbalance in the omega-6/omega-3 fatty acid ratio. Compared to mucosa and serum samples, fecal samples might have more advantages in lipidomics studies due to the convenience of sample collection and effectiveness in reflecting metabolic information. [ABSTRACT FROM AUTHOR]

Background: Infertility is a major health issue, affecting 15% of reproductive‐age couples with male factors contributing to 50% of cases. Asthenozoospermia (AS), or low sperm motility, is a common cause of male infertility with complex aetiology, involving genetic and metabolic alterations, inflammation and oxidative stress. However, the molecular mechanisms behind low motility are unclear. In this study, we used a metabolomics approach to identify metabolic biomarkers and pathways involved in sperm motility. Methods: We compared the metabolome and lipidome of spermatozoa of men with normozoospermia (n = 44) and AS (n = 22) using untargeted LC–MS and the metabolome of seminal fluid using 1H‐NMR. Additionally, we evaluated the seminal fluid redox status to assess the oxidative stress in the ejaculate. Results: We identified 112 metabolites and 209 lipids in spermatozoa and 27 metabolites in the seminal fluid of normozoospermic and asthenozoospermic men. PCA analysis of the spermatozoa's metabolomics and lipidomics data showed a clear separation between groups. Spermatozoa of asthenozoospermic men presented lower levels of several amino acids, and increased levels of energetic substrates and lysophospholipids. However, the metabolome and redox status of the seminal fluid was not altered inAS. Conclusions: Our results indicate impaired metabolic pathways associated with redox homeostasis and amino acid, energy and lipid metabolism in AS. Taken together, these findings suggest that the metabolome and lipidome of human spermatozoa are key factors influencing their motility and that oxidative stress exposure during spermatogenesis or sperm maturation may be in the aetiology of decreased motility in AS. [ABSTRACT FROM AUTHOR]

[Display omitted] • A panel of seven lipids increased c-statistic by an increment of 0.077, the greatest added value for prediction of incident CVD ever achieved by prospective lipidomics studies to the best of our knowledge. • Considerable mediations were observed through SM 41:1b, presumably SM(d18:1/23:0), in the associations between established cardiovascular risk factors and CHD risk, diabetes in particular. • CHD risk associated with increased levels of PC 36:0a, SM 41:1b, LPC 18:0 and LPC 20:3, and decreased levels of CE 18:2 were aggravated by long-term exposure to ambient air pollution. Previous lipidomics studies have identified various lipid predictors for cardiovascular risk, however, with limited predictive increment, sometimes using too many predictor variables at the expense of practical efficiency. To search for lipid predictors of future coronary heart disease (CHD) with stronger predictive power and efficiency to guide primary intervention. We conducted a prospective nested case-control study involving 1,621 incident CHD cases and 1:1 matched controls. Lipid profiling of 161 lipid species for baseline fasting plasma was performed by liquid chromatography-mass spectrometry. In search of CHD predictors, seven lipids were selected by elastic-net regression during over 90% of 1000 cross-validation repetitions, and the derived composite lipid score showed an adjusted odds ratio of 3.75 (95% confidence interval: 3.15, 4.46) per standard deviation increase. Addition of the lipid score into traditional risk model increased c-statistic to 0.736 by an increment of 0.077 (0.063, 0.092). From the seven lipids, we found mediation of CHD risk from baseline diabetes through sphingomyelin (SM) 41:1b with a considerable mediation proportion of 36.97% (P < 0.05). We further found that the positive associations of phosphatidylcholine (PC) 36:0a, SM 41:1b, lysophosphatidylcholine (LPC) 18:0 and LPC 20:3 were more pronounced among participants with higher exposure to fine particulate matter or its certain components, also to ozone for LPC 18:0 and LPC 20:3, while the negative association of cholesteryl ester (CE) 18:2 was attenuated with higher black carbon exposure (P < 0.05). We identified seven lipid species with greatest predictive increment so-far achieved for incident CHD, and also found novel biomarkers for CHD risk stratification among individuals with diabetes or heavy air pollution exposure. [ABSTRACT FROM AUTHOR]

Normal-weight obesity (NWO) and normal-weight central obesity (NWCO) have been linked to higher cardiometabolic risks, but their etiological bases and attributable dietary factors remain unclear. In this study we therefore aimed to identify lipidomic signatures and dietary factors related to NWO and NWCO and to explore the mediation associations of lipids in diet–adiposity associations. Using a high-coverage targeted lipidomic approach, we quantified 1245 serum lipids in participants with NWO (n = 150), NWCO (n = 150), or propensity-score-matched normal-weight controls (n = 150) based on the Regional Ethnic Cohort Study in Northwest China. Consumption frequency of 28 major food items was recorded using a food frequency questionnaire. Profound lipidomic perturbations of NWCO relative to NWO were observed, and 249 (dominantly glycerolipids) as well as 48 (dominantly glycerophospholipids) lipids were exclusively associated with NWCO or NWO. Based on strong lipidomic signatures identified by a LASSO model, phospholipid biosynthesis was the top enriched pathway of NWCO, and sphingolipid metabolism was the top pathway of NWO. Remarkably, sphingolipids were positively associated with NWO and NWCO, but lyso-phosphatidylcholines were negatively associated with them. Rice, fruit juice, and carbonated drink intakes were positively associated with the risk of NWCO. Both global and individual lipidomic signatures, including SE(28:1_22:6) and HexCer(d18:1/20:1), mediated these diet-NWCO associations (mediation proportion: 15.92%–26.10%). Differential lipidomic signatures were identified for overall and abdominal adiposity accumulation in normal-weight individuals, underlining their core mediation roles in dietary contributions to adiposity deposition. [ABSTRACT FROM AUTHOR]

Secondary lymphedema (LE) following breast cancer‐related surgery is a life‐long complication, which currently has no cure. LE induces significant regional adipose tissue deposition, requiring liposuction as a treatment. Here, we aimed to elucidate the transcriptional, metabolomic, and lipidomic signature of the adipose tissue developed due to the surgery‐induced LE in short‐ and long‐term LE patients and compared the transcriptomic landscape of LE adipose tissue to the obesity‐induced adipose tissue. Adipose tissue biopsies were obtained from breast cancer‐operated females with LE from the affected and non‐affected arms (n = 20 patients). To decipher the molecular properties of the LE adipose tissue, we performed RNA sequencing, metabolomics, and lipidomics combined with bioinformatics analyses. Differential gene expression data from a cohort of lean and obese patients without LE was used for comparisons. Integrative analysis of functional genomics revealed that inflammatory response, cell chemotaxis, and angiogenesis were upregulated biological processes in the LE arm, indicating a sustained inflammation in the edematous adipose tissue; whereas, epidermal differentiation, cell–cell junction organization, water homeostasis, and neurogenesis were downregulated in the LE arm. Surprisingly, only a few genes were found to be the same in the LE‐induced and the obesity‐induced adipose tissue expansion, indicating a different type of adipose tissue development in these two conditions. In metabolomics analysis, we found reduced levels of a branched‐chain amino acid valine in the LE arm and downregulation of the mRNA levels of its transporter SLC6A15. Lipidomics analyses did not show any significant differences between the LE and non‐LE arms, suggesting that other factors affect the lipid composition of the adipose tissue more than the LE in these patients. Our results provide a detailed molecular characterization of adipose tissue in secondary LE after breast cancer‐related surgery. We also show distinct differences in transcriptomic signatures between LE‐induced adipose tissue and obesity‐induced adipose tissue, but only minor differences in metabolome and lipidome between the LE and the non‐LE arm. [ABSTRACT FROM AUTHOR]

Aim Methods Results Conclusion Diabetes is increasing in prevalence worldwide, with a 20% rise in prevalence predicted between 2021 and 2030, bringing an increased burden of complications, such as diabetic kidney disease (DKD). DKD is a leading cause of end‐stage kidney disease, with significant impacts on patients, families and healthcare providers. DKD often goes undetected until later stages, due to asymptomatic disease, non‐standard presentation or progression, and sub‐optimal screening tools and/or provision. Deeper insights are needed to improve DKD diagnosis, facilitating the identification of higher‐risk patients. Improved tools to stratify patients based on disease prognosis would facilitate the optimisation of resources and the individualisation of care. This review aimed to identify how multiomic approaches provide an opportunity to understand the complex underlying biology of DKD.This review explores how multiomic analyses of DKD are improving our understanding of DKD pathology, and aiding in the identification of novel biomarkers to detect disease earlier or predict trajectories.Effective multiomic data integration allows novel interactions to be uncovered and empathises the need for harmonised studies and the incorporation of additional data types, such as co‐morbidity, environmental and demographic data to understand DKD complexity. This will facilitate a better understanding of kidney health inequalities, such as social‐, ethnicity‐ and sex‐related differences in DKD risk, onset and progression.Multiomics provides opportunities to uncover how lifetime exposures become molecularly embodied to impact kidney health. Such insights would advance DKD diagnosis and treatment, inform preventative strategies and reduce the global impact of this disease. [ABSTRACT FROM AUTHOR]

Plant-pathogenic bacteria are one of the major constraints on agricultural yield. In order to selectively treat these bacteria, it is essential to understand the molecular structure of their cell membrane. Previous studies have focused on analyzing hydrolyzed fatty acids (FA) due to the complexity of bacterial membrane lipids. These studies have highlighted the occurrence of branched-chain fatty acids (BCFA) alongside normal-chain fatty acids (NCFA) in many bacteria. As several FA are bound in the intact phospholipids of the bacterial membrane, the presence of isomeric FA complicates lipid analysis. Furthermore, commercially available reference standards do not fully cover potential lipid isomers. To address this issue, we have developed a reversed-phase high-performance liquid chromatography (RP-HPLC) method with tandem mass spectrometry (MS/MS) to analyze the phospholipids of various plant-pathogenic bacteria with a focus on BCFA containing phospholipids. The study revealed the separation of three isomeric phosphatidylethanolamines (PE) depending on the number of bound BCFA to NCFA. The validation of the retention order was based on available reference standards in combination with the analysis of hydrolyzed fatty acids through gas chromatography with mass spectrometry (GC/MS) after fractionation. Additionally, the transferability of the retention order to other major lipid classes, such as phosphatidylglycerols (PG) and cardiolipins (CL), was thoroughly examined. Using the information regarding the retention behavior, the phospholipid profile of six plant-pathogenic bacteria was structurally elucidated. Furthermore, the developed LC–MS/MS method was used to classify the plant-pathogenic bacteria based on the number of bound BCFA in the phospholipidome. [ABSTRACT FROM AUTHOR]

In recent years, instrumental improvements have enabled the spread of mass spectrometry–based lipidomics platforms in biomedical research. In mass spectrometry, the reliability of generated data varies for each compound, contingent on, among other factors, the availability of labeled internal standards. It is challenging to evaluate the data for lipids without specific labeled internal standards, especially when dozens to hundreds of lipids are measured simultaneously. Thus, evaluation of the performance of these platforms at the individual lipid level in interlaboratory studies is generally not feasible in a time-effective manner. Herein, using a focused subset of sphingolipids, we present an in-house validation methodology for individual lipid reliability assessment, tailored to the statistical analysis to be applied. Moreover, this approach enables the evaluation of various methodological aspects, including discerning coelutions sharing identical selected reaction monitoring transitions, pinpointing optimal labeled internal standards and their concentrations, and evaluating different extraction techniques. While the full validation according to analytical guidelines for all lipids included in a lipidomics method is currently not possible, this process shows areas to focus on for subsequent method development iterations as well as the robustness of data generated across diverse methodologies. [ABSTRACT FROM AUTHOR]

High-resolution ion mobility (resolving power > 200) coupled with mass spectrometry (MS) is a powerful analytical tool for resolving isobars and isomers in complex samples. High-resolution ion mobility is capable of discerning additional structurally distinct features, which are not observed with conventional resolving power ion mobility (IM, resolving power ~ 50) techniques such as traveling wave IM and drift tube ion mobility (DTIM). DTIM in particular is considered to be the "gold standard" IM technique since collision cross section (CCS) values are directly obtained through a first-principles relationship, whereas traveling wave IM techniques require an additional calibration strategy to determine accurate CCS values. In this study, we aim to evaluate the separation capabilities of a traveling wave ion mobility structures for lossless ion manipulation platform integrated with mass spectrometry analysis (SLIM IM-MS) for both lipid isomer standards and complex lipid samples. A cross-platform investigation of seven subclass-specific lipid extracts examined by both DTIM-MS and SLIM IM-MS showed additional features were observed for all lipid extracts when examined under high resolving power IM conditions, with the number of CCS-aligned features that resolve into additional peaks from DTIM-MS to SLIM IM-MS analysis varying between 5 and 50%, depending on the specific lipid sub-class investigated. Lipid CCS values are obtained from SLIM IM (TW(SLIM)CCS) through a two-step calibration procedure to align these measurements to within 2% average bias to reference values obtained via DTIM (DTCCS). A total of 225 lipid features from seven lipid extracts are subsequently identified in the high resolving power IM analysis by a combination of accurate mass-to-charge, CCS, retention time, and linear mobility-mass correlations to curate a high-resolution IM lipid structural atlas. These results emphasize the high isomeric complexity present in lipidomic samples and underscore the need for multiple analytical stages of separation operated at high resolution. [ABSTRACT FROM AUTHOR]

The importance of lipids in biology continues to grow with their recent linkages to more diseases and conditions, microbiome fluctuations, and environmental exposures. These associations have motivated researchers to evaluate lipidomic changes in numerous matrices and studies. Lipidomic analyses, however, present numerous challenges as lipid species have broad chemistries that require different extraction methods and instrumental analyses to evaluate and separate their many isomers and isobars. Increasing knowledge about different lipid characteristics is therefore crucial for improving their separation and identification. Here, we present a multidimensional database for lipids analyzed on a platform combining reversed-phase liquid chromatography, drift tube ion mobility spectrometry, collision-induced dissociation, and mass spectrometry (RPLC-DTIMS-CID-MS). This platform and the different separation characteristics it provides enables more confident lipid annotations when compared to traditional tandem mass spectrometry platforms, especially when analyzing highly isomeric molecules such as lipids. This database expands on our previous publication containing only human plasma and bronchoalveolar lavage fluid lipids and provides experimental RPLC retention times, IMS collision cross section (CCS) values, and m/z information for 877 unique lipids from additional biofluids and tissues. Specifically, the database contains 1504 precursor [M + H]+, [M + NH4]+, [M + Na]+, [M-H]−, [M-2H]2−, [M + HCOO]−, and [M + CH3COO]− ion species and their associated CID fragments which are commonly targeted in clinical and environmental studies, in addition to being present in the chloroform layer of Folch extractions. Furthermore, this multidimensional RPLC-DTIMS-CID-MS database spans 5 lipid categories (fatty acids, sterols, sphingolipids, glycerolipids, and glycerophospholipids) and 24 lipid classes. We have also created a webpage (tarheels.live/bakerlab/databases/) to enhance the accessibility of this resource which will be populated regularly with new lipids as we identify additional species and integrate novel standards. [ABSTRACT FROM AUTHOR]

C-type lectin receptors (CLRs), which are pattern recognition receptors responsible for triggering innate immune responses, recognize damaged self-components and immunostimulatory lipids from pathogenic bacteria; however, several of their ligands remain unknown. Here, we propose a new analytical platform combining liquid chromatography-high-resolution tandem mass spectrometry with microfractionation capability (LC-FRC-HRMS/MS) and a reporter cell assay for sensitive activity measurements to develop an efficient methodology for searching for lipid ligands of CLR from microbial trace samples (crude cell extracts of approximately 5 mg dry cell/mL). We also developed an in-house lipidomic library containing accurate mass and fragmentation patterns of more than 10,000 lipid molecules predicted in silico for 90 lipid subclasses and 35 acyl side chain fatty acids. Using the developed LC-FRC-HRMS/MS system, the lipid extracts of Helicobacter pylori were separated and fractionated, and HRMS and HRMS/MS spectra were obtained simultaneously. The fractionated lipid extract samples in 96-well plates were thereafter subjected to reporter cell assays using nuclear factor of activated T cells (NFAT)-green fluorescent protein (GFP) reporter cells expressing mouse or human macrophage-inducible C-type lectin (Mincle). A total of 102 lipid molecules from all fractions were annotated using an in-house lipidomic library. Furthermore, a fraction that exhibited significant activity in the NFAT-GFP reporter cell assay contained α-cholesteryl glucoside, a type of glycolipid, which was successfully identified as a lipid ligand molecule for Mincle. Our analytical platform has the potential to be a useful tool for efficient discovery of lipid ligands for immunoreceptors. [ABSTRACT FROM AUTHOR]

Ulcerative colitis (UC) is an inflammatory bowel disease characterized by recurrent inflammatory tissue damage to the intestinal mucosa and forming intestinal epithelial ulcers. It is one of the most intractable diseases in the world. To date, the mechanism is unclear. Causonis japonica (Thunb.) Raf. (Wu Lianmei in Chinese; WLM), a traditional Chinese medicine, which has a long history as an anti-inflammatory, but its effect on UC was unconfirmed yet. Therefore, we established a dextran sodium sulfate (DSS)-induced UC mice model and evaluated the therapeutic effect of WLM extract. The results indicated that WLM inhibits DSS-induced inflammatory response in colitis in vivo, decrease DSS-induced clinical manifestations, reverses colon length shortening, and reduces tissue damage. The results of ELISA kits suggested that WLM could reverse the levels of DSS-induced inflammatory factors. To explore the mechanism of WLM in treating DSS-induced UC, ¹H NMR and UHPLC-Q/ Orbitrap MS were used to perform non-targeted metabolomics analysis; 21 differential metabolites in colon tissues were closely related to UC. Meanwhile, the pseudo-targeted lipidomics based on UHPLC-Q/Trap MS was used to analyze lipid metabolism disorders, and 60 differential lipid compounds were screened. These differential compounds were mainly involved in glycerophospholipid, arachidonic acid, glycerolipid, citric acid, tyrosine, and ether lipid metabolisms. The analysis of gut microbial showed that WLM may improve the symptoms of UC mice by reducing the abundance of Helicobacter and Streptococcus and increasing the abundance of Limosilactobacillus and Akkermansia. Moreover, the real-time qPCR results showed that WLM extract could decrease the mRNA levels of inflammatory factors and may be associated with protecting the integrity of intestinal mucosal barrier by destroying in vivo metabolic pathways, especially by regulating energy and lipid metabolisms and reducing inflammatory reactions. It provides a beneficial reference for studying WLM to elucidate the therapeutic mechanism of UC. [ABSTRACT FROM AUTHOR]

Aberrant lipid metabolism has been widely recognized as a hallmark of various diseases. However, the comprehensive analysis of distinct lipids is challenging due to the complexity of lipid molecular structures, wide concentration ranges, and numerous isobaric and isomeric lipids. Usually, liquid chromatography-mass spectrometry (LC-MS)-based lipidomics requires a long time for chromatographic separation to achieve optimal separation and selectivity. Ion mobility (IM) adds a new separation dimension to LC-MS, significantly enhancing the coverage, sensitivity, and resolving power. We took advantage of the rapid separation provided by ion mobility and optimized a fast and broad-coverage lipidomics method using the LC-IM-MS technology. The method required only 8 minutes for separation and detected over 1000 lipid molecules in a single analysis of common biological samples. The high reproducibility and accurate quantification of this high-throughput lipidomics method were systematically characterized. We then applied the method to comprehensively measure dysregulated lipid metabolism in patients with colorectal cancer (CRC). Our results revealed 115 significantly changed lipid species between preoperative and postoperative plasma of patients with CRC and also disclosed associated differences in lipid classes such as phosphatidylcholines (PC), sphingomyelins (SM), and triglycerides (TG) regarding carbon number and double bond. Together, a fast and broad-coverage lipidomics method was developed using ion mobility-mass spectrometry. This method is feasible for large-scale clinical lipidomic studies, as it effectively balances the requirements of high-throughput and broad-coverage in clinical studies. [ABSTRACT FROM AUTHOR]

Background: Mesenchymal stromal cell derived extracellular vesicles (MSC-EVs) are a promising therapeutic for neuroinflammation. MSC-EVs can interact with microglia, the resident immune cells of the brain, to exert their immunomodulatory effects. In response to inflammatory cues, such as cytokines, microglia undergo phenotypic changes indicative of their function e.g. morphology and secretion. However, these changes in response to MSC-EVs are not well understood. Additionally, no disease-relevant screening tools to assess MSC-EV bioactivity exist, which has further impeded clinical translation. Here, we developed a quantitative, high throughput morphological profiling approach to assess the response of microglia to neuroinflammation- relevant signals and whether this morphological response can be used to indicate the bioactivity of MSC-EVs. Results: Using an immortalized human microglia cell-line, we observed increased size (perimeter, major axis length) and complexity (form factor) upon stimulation with interferon-gamma (IFN-γ) and tumor necrosis factor-alpha (TNF-α). Upon treatment with MSC-EVs, the overall morphological score (determined using principal component analysis) shifted towards the unstimulated morphology, indicating that MSC-EVs are bioactive and modulate microglia. The morphological effects of MSC-EVs in TNF-α /IFN-γ stimulated cells were concomitant with reduced secretion of 14 chemokines/cytokines (e.g. CXCL6, CXCL9) and increased secretion of 12 chemokines/cytokines (e.g. CXCL8, CXCL10). Proteomic analysis of cell lysates revealed significant increases in 192 proteins (e.g. HIBADH, MEAK7, LAMC1) and decreases in 257 proteins (e.g. PTEN, TOM1, MFF) with MSC-EV treatment. Of note, many of these proteins are involved in regulation of cell morphology and migration. Gene Set Variation Analysis revealed upregulation of pathways associated with immune response, such as regulation of cytokine production, immune cell infiltration (e.g. T cells, NK cells) and morphological changes (e.g. Semaphorin, RHO/Rac signaling). Additionally, changes in microglia mitochondrial morphology were measured suggesting that MSC-EV modulate mitochondrial metabolism. Conclusion: This study comprehensively demonstrates the effects of MSC-EVs on human microglial morphology, cytokine secretion, cellular proteome, and mitochondrial content. Our high-throughput, rapid, low-cost morphometric approach enables screening of MSC-EV batches and manufacturing conditions to enhance EV function and mitigate EV functional heterogeneity in a disease relevant manner. This approach is highly generalizable and can be further adapted and refined based on selection of the disease-relevant signal, target cell, and therapeutic product. [ABSTRACT FROM AUTHOR]

ABSTRACT Peach Leaf Curl Disease, caused by Taphrina deformans, is characterized by reddish hypertrophic and hyperplasic leaf areas. To comprehend the biochemical imbalances caused by the fungus, dissected symptomatic (C) and asymptomatic areas (N) from leaves with increasing disease extension were analyzed by an integrated approach including metabolomics, lipidomics, proteomics, and complementary biochemical techniques. Drastic metabolic differences were identified in C areas with respect to either N areas or healthy leaves, including altered chloroplastic functioning and composition, which differs from the typical senescence process. In C areas, alteration in redox‐homoeostasis proteins and in triacylglycerols content, peroxidation and double bond index were observed. Proteomic data revealed induction of host enzymes involved in auxin and jasmonate biosynthesis and an upregulation of phenylpropanoid and mevalonate pathways and downregulation of the plastidic methylerythritol phosphate route. Amino acid pools were affected, with upregulation of proteins involved in asparagine synthesis. Curled areas exhibited a metabolic shift towards functioning as a sink tissue importing sugars, probably from N areas, and producing energy through fermentation and respiration and reductive power via the pentose phosphate route. Identifying the metabolic disturbances leading to disease symptoms is a key step in designing strategies to prevent or delay the progression of the disease. [ABSTRACT FROM AUTHOR]

Osteomyelitis occurs when Staphylococcus aureus invades the bone microenvironment, resulting in a bone marrow abscess with a spatially defined architecture of cells and biomolecules. Imaging mass spectrometry and microscopy are tools that can be employed to interrogate the lipidome of S. aureus -infected murine femurs and reveal metabolic and signaling consequences of infection. Here, nearly 250 lipids were spatially mapped to healthy and infection-associated morphological features throughout the femur, establishing composition profiles for tissue types. Ether lipids and arachidonoyl lipids were altered between cells and tissue structures in abscesses, suggesting their roles in abscess formation and inflammatory signaling. Sterols, triglycerides, bis(monoacylglycero)phosphates, and gangliosides possessed ring-like distributions throughout the abscess, suggesting a hypothesized dysregulation of lipid metabolism in a population of cells that cannot be discerned with traditional microscopy. These data provide insight into the signaling function and metabolism of cells in the fibrotic border of abscesses, likely characteristic of lipid-laden macrophages. [Display omitted] • Lipids are spatially mapped to tissue types throughout an S. aureus -infected femur • Multimodal MALDI IMS uncovers lipid dynamics between bacteria and leukocytes • Molecular phenotyping suggests lipid-laden macrophages in a bone marrow abscess Good et al. present lipidomics data directly acquired from infected murine femurs, providing a unique insight into the molecular and cellular environment driving the complex pathology of bone infections. This multimodal molecular imaging approach is valuable for understanding the mechanisms by which S. aureus evades immune clearance in bone tissue. [ABSTRACT FROM AUTHOR]

The lipidomic secretions of embryos provide a unique opportunity to examine the cellular processes of the early conceptus. In this study we profiled lipids released by the early equine conceptus, using high-resolution mass spectrometry to detect individual lipid species. This study examined the lipidomic profile in embryo-conditioned media from in vivo-produced, 8-9 day-old equine embryos (n = 3) cultured in vitro for 36 h, analyzed over 3 timepoints. A total of 1,077 lipid IDs were recorded across all samples, containing predominantly glycerolipids. Seventy-nine of these were significantly altered in embryo conditioned-media versus media only control (p < 0.05, fold-change >2 or < 0.5). Fifty-five lipids were found to be released into the embryo-conditioned media, of which 54.5% were triacylglycerols and 23.6% were ceramides. The sterol lipid, cholesterol, was also identified and secreted in significant amounts as embryos developed. Further, 24 lipids were found to be depleted from the media during culture, of which 70.8% were diacylglycerols, 16.7% were triacylglycerols and 12.5% were ceramides. As lipid-free media contained consistently detectable lipid peaks, a further profile analysis of the various components of non-embryo-conditioned media consistently showed the presence of 137 lipids. Lipid peaks in non-embryo-conditioned media increased in response to incubation under mineral oil, and contained ceramides, diacylglycerols and triacylglycerols. These results emphasize the importance of a defined embryo culture medium and a need to identify the lipid requirements of the embryo precisely. This study sheds light on early embryo lipid metabolism and the transfer of lipids during in vitro culture. [ABSTRACT FROM AUTHOR]

Understanding the systemic biochemistry of early pregnancy in the mare is essential for developing new diagnostics and identifying causes for pregnancy loss. This study aimed to elucidate the dynamic lipidomic changes occurring during the initial stages of equine pregnancy, with a specific focus on days 7 and 14 post-ovulation. By analysing and comparing the plasma lipid profiles of pregnant and non-pregnant mares, the objective of this study was to identify potential biomarkers for pregnancy and gain insights into the biochemical adaptations essential for supporting maternal recognition of pregnancy and early embryonic development. Employing discovery lipidomics, we analysed plasma samples from pregnant and non-pregnant mares on days 7 and 14 post-conception using the SCIEX ZenoTOF 7600 system. This high-resolution mass spectrometry approach enabled us to comprehensively profile and compare the lipidomes across these critical early gestational timepoints. Our analysis revealed significant lipidomic alterations between pregnant and non-pregnant mares and between days 7 and 14 of pregnancy. Key findings include the upregulation of bile acids, sphingomyelins, phosphatidylinositols, and triglycerides in pregnant mares. These changes suggest enhanced lipid synthesis and mobilization, likely associated with the embryo's nutritional requirements and the establishment of embryo–maternal interactions. There were significant differences in lipid metabolism between pregnant and non-pregnant mares, with a notable increase in the sterol lipid BA 24:1;O5 in pregnant mares as early as day 7 of gestation, suggesting it as a sensitive biomarker for early pregnancy detection. Notably, the transition from day 7 to day 14 in pregnant mares is characterized by a shift towards lipids indicative of membrane biosynthesis, signalling activity, and preparation for implantation. The study demonstrates the profound lipidomic shifts that occur in early equine pregnancy, highlighting the critical role of lipid metabolism in supporting embryonic development. These findings provide valuable insights into the metabolic adaptations during these period and potential biomarkers for early pregnancy detection in mares. [ABSTRACT FROM AUTHOR]

Background Objectives Methods Results Conclusions Limonene and linalool are used in cosmetic products for their floral scents, but their oxidation products are strong contact allergens whose mechanisms of action are still not fully understood.The effects of limonene hydroperoxide (Lim‐2‐OOH) and linalool hydroperoxides (Lin‐6/7‐OOH) on the lipid profile of a human keratinocyte cell line (HaCaT) were evaluated. 2,4‐Dinitrofluorobenzene (DNFB) was also included.Lim‐2‐OOH and Lin‐6/7‐OOH were synthesised according to previous methods. HaCaT cells were treated with allergens (10 μM) for 24 h and the cellular lipid extracts were analysed by C18 liquid chromatography with tandem mass spectrometry (LC–MS/MS). Data analysis was performed using Lipostar software. Statistical analysis was carried out using Metaboanalyst and R software.All three sensitisers used caused significant changes in the lipidome of HaCaT cells in a similar trend. There was an upregulation in several plasmanyl/plasmenyl phospholipids (O‐/P‐phosphatidylcholines [PC] and O‐/P‐phosphatidylethanolamines [PE]), sphingolipids (HexCer) and triacylglycerol lipid species, and a decrease in some polyunsaturated fatty acids‐containing phospholipid (PE and PC) species suggesting oxidative stress and inflammation.This study is the first to evaluate the plasticity of the HaCaT cell lipidome in response to allylic hydroperoxide allergens Lim‐2‐OOH and Lin‐6/7‐OOH, together with the experimental contact allergen DNFB. These allergens are able to upregulate and downregulate certain lipid classes to a varying degree. [ABSTRACT FROM AUTHOR]

Background: Severe fever with thrombocytopenia syndrome (SFTS) is a rapidly progressing infectious disease with a high fatality rate caused by a novel bunyavirus (SFTSV). The role of lipids in viral infections is well-documented; however, the specific alterations in lipid metabolism during SFTSV infection remain elusive. This study aims to elucidate the lipid metabolic dysregulations in the early stages of SFTS patients. Methods: This study prospectively collected peripheral blood sera from 11 critical SFTS patients, 37 mild SFTS patients, and 23 healthy controls during the early stages of infection for lipidomics analysis. A systematic bioinformatics analysis was conducted from three aspects integrating lipid differential expressions, lipid differential correlations, and lipid-clinical indices correlations to reveal the serum lipid metabolic dysregulation in SFTSV-infected individuals. Results: Our findings reveal significant lipid metabolic dysregulation in SFTS patients. Specifically, compared to healthy controls, SFTS patients exhibited three distinct modes of lipid differential expression: increased levels of lipids including phosphatidylserine (PS), hexosylceramide (HexCer), and triglycerides (TG); decreased levels of lipids including lysophosphatidylcholine (LPC), acylcarnitine (AcCa), and cholesterol esters (ChE); and lipids showing "dual changes" including phosphatidylcholine (PC) and phosphatidylethanolamine (PE). Finally, based on lipid metabolic pathways and literature analysis, we systematically elucidated the potential mechanisms underlying lipid metabolic dysregulation in the early stage of SFTSV infection. Conclusions: Our study presents the first global serum lipidome profile and reveals the lipid metabolic dysregulation patterns in the early stage of SFTSV infection. These findings provide a new basis for the diagnosis, treatment, and further investigation of the disease. [ABSTRACT FROM AUTHOR]

Dunaliella salina is a green microalga extensively explored for β-carotene production, while knowledge of its lipid composition is still limited and poorly investigated. Among lipids, polar lipids have been highlighted as bioactive phytochemicals with health-promoting properties. This research aimed to provide an in-depth lipidome profiling of D. salina using liquid and gas chromatography coupled with mass spectrometry. The lipid content was 6.8%, including phospholipids, glycolipids, betaine lipids, sphingolipids, triglycerides, diglycerides, and pigments. Among the total esterified fatty acids, 13.6% were 18:3 omega-3 and 14.7% were 18:1 omega-9. The lipid extract of D. salina showed anti-inflammatory activity by inhibiting cyclooxygenase-2 activity at 100 µg/mL, dose-dependent antioxidant scavenging activity, and antidiabetic activity by inhibiting α-glucosidase activity at 25 and 125 µg/mL. In conclusion, the lipid extract of D. salina has the potential to be used as a functional food ingredient or in the nutraceutical and cosmeceutical industries. [ABSTRACT FROM AUTHOR]

Introduction: At least one-third of the identified risk alleles from Genome-Wide Association Studies (GWAS) of Alzheimer's disease (AD) are involved in lipid metabolism, lipid transport, or direct lipid binding. In fact, a common genetic variant (e4) in a cholesterol and phospholipid transporter, Apolipoprotein E (APOEe4), is the primary genetic risk factor for late-onset AD. In addition to genetic variants, lipidomic studies have reported severe metabolic dysregulation in human autopsy brain tissue, cerebrospinal fluid, blood, and multiple mouse models of AD. Methods: We aimed to identify an overarching metabolic pathway in lipid metabolism by integrating analyses of lipidomics and transcriptomics from the Religious Order Study and Rush Memory Aging Project (ROSMAP) using differential analysis and network correlation analysis. Results: Coordinated differences in lipids were found to be dysregulated in association with both mild cognitive impairment (MCI) and APOEe4 carriers. Interestingly, these correlations were weakened when adjusting for education. Indeed, the cognitively non-impaired APOEe4 carriers have higher education levels in the ROSMAP cohort, suggesting that this lipid signature may be associated with a resilience phenotype. Network correlation analysis identified multiple differential lipids within a single module that are substrates and products in the Lands Cycle for acyl chain remodeling. In addition, our analyses identified multiple genes in the Lands Cycle acyl chain remodeling pathway, which were associated with cognitive decline independent of amyloid-ß (Aß) load and tau tangle pathologies. Discussion: Our studies highlight the critical differences in acyl chain remodeling in brain tissue from APOEe4 carriers and individual non-carriers with MCI. A coordinated lipid profile shift in dorsolateral prefrontal cortex from both APOEe4 carriers and MCI suggests differences in lipid metabolism occur early in disease stage and highlights lipid homeostasis as a tractable target for early disease modifying intervention. [ABSTRACT FROM AUTHOR]

Background: Slow transit constipation (STC) is highly prevalent and has rising incidence. Shouhui Tongbian capsule (SHTB) is a traditional Chinese Medicine formula with extensive and highly efficacious usage in STC treatment, however, its mechanism of action, especially the regulation of microbiome and lipid metabolites, remains unclear. Methods: After quality control of SHTB using LC‒MS to obtain its material basis, we tried to elucidate the cohesive modulatory network of SHTB against STC using hyphenated methods from microbiomics, lipidomics, mass spectrometry imaging (MSI) and molecular methods. Results: SHTB could repair intestinal barrier damage, reduce systemic inflammation and increase intestinal motility in a diphenoxylate-induced STC rat model. Based on 16S rDNA sequencing results, SHTB rehabilitated the abnormal changes in Alloprevotella, Coprococcus, Marvinbryantia, etc., which were associated with STC symptoms. Meanwhile, microbial functional prediction showed that lipid metabolism was improved with SHTB administration. The differential lipids, including fatty acids, lysophosphatidylcholine, phosphatidylcholine, sphingomyelin triglyceride and ceramide, that are closely related to STC disease and SHTB efficacy. Furthermore, SHTB significantly reversed the abnormal expression of these key target enzymes in colon samples, including CTP-phosphocholine cytidylyltransferase, CTP-phosphoethanolamine cytidylyltransferase, phosphatidic acid phosphatase, acid sphingomyelinase etc. Conclusions: Combined analysis demonstrated that SHTB reducing lipid accumulation and recovery of intestinal microbial homeostasis was the critical mechanism by which SHTB treats STC. [ABSTRACT FROM AUTHOR]

Multiple sclerosis (MS) is a complex chronic neuroinflammatory disease characterized by demyelination leading to neuronal dysfunction and neurodegeneration manifested by various neurological impairments. The endocannabinoid system (ECS) is a lipid signalling network, which plays multiple roles in the central nervous system and the periphery, including synaptic signal transmission and modulation of inflammation. The ECS has been identified as a potential target for the development of novel therapeutic interventions in MS patients. It remains unclear whether ECS-associated metabolites are changed in MS and could serve as biomarkers in blood or cerebrospinal fluid (CSF). In this retrospective study we applied targeted lipidomics to matching CSF and serum samples of 74 MS and 80 non-neuroinflammatory control patients. We found that MS-associated lipidomic changes overall did not coincide between CSF and serum. While glucocorticoids correlated positively, only the endocannabinoid (eCB) 2-arachidonoyl glycerol (2-AG) showed a weak positive correlation (r = 0.3, p < 0.05) between CSF and serum. Peptide endocannabinoids could be quantified for the first time in CSF but did not differ between MS and controls. MS patients showed elevated levels of prostaglandin E2 and steaorylethanolamide in serum, and 2-oleoylglycerol and cortisol in CSF. Sex-specific differences were found in CSF of MS patients showing increased levels of 2-AG and glucocorticoids in males only. Overall, arachidonic acid was elevated in CSF of males. Interestingly, CSF eCBs correlated positively with age only in the control patients due to the increased levels of eCBs in young relapsing-remitting MS patients. Our findings reveal significant discrepancies between CSF and serum, underscoring that measuring eCBs in blood matrices is not optimal for detecting MS-associated changes in the central nervous system. The identified sex and age-specific changes of analytes of the stress axis and ECS specifically in the CSF of MS patients supports the role of the ECS in MS and may be relevant for drug development strategies. [ABSTRACT FROM AUTHOR]

Psoriasis is an inflammatory skin disease associated with an impaired skin barrier. The skin barrier function is dependent on the extracellular lipid matrix which surrounds the corneocytes in the stratum corneum. Ceramides comprise essential components of this matrix. Alterations in the stratum corneum ceramide profile have been directly linked to barrier dysfunction and might be an underlying factor of the barrier impairment in psoriasis. In this study, we investigated the ceramide profile and barrier function in psoriasis. Lesional and non‐lesional skin of 26 patients and 10 healthy controls were analysed using in‐depth ceramide lipidomics by liquid chromatography‐mass spectrometry. Barrier function was assessed by measuring transepidermal water loss. Lesional skin showed a significant decrease in the abundance of total ceramides with significant alterations in the ceramide subclass composition compared to control and non‐lesional skin. Additionally, the percentage of monounsaturated ceramides was significantly increased, and the average ceramide chain length significantly decreased in lesional skin. Altogether, this resulted in a markedly different profile compared to controls for lesional skin, but not for non‐lesional skin. Importantly, the reduced barrier function in lesional psoriasis correlated to alterations in the ceramide profile, highlighting their interdependence. By assessing the parameters 2 weeks apart, we are able to highlight the reproducibility of these findings, which further affirms this connection. To conclude, we show that changes in the ceramide profile and barrier impairment are observed in, and limited to, lesional psoriatic skin. Their direct correlation provides a further mechanistic basis for the concomitantly observed impairment of barrier dysfunction. [ABSTRACT FROM AUTHOR]

Schizophrenia (SCH) is a major mental illness that causes impaired cognitive function and long-term disability, so the requirements for reliable biomarkers for early diagnosis and therapy of SCH are essential. The objective of this work was an untargeted lipidomic study of serum samples from a Serbian cohort including 30 schizophrenia (SCH) patients and 31 non-psychiatric control (C) individuals by applying liquid chromatography (LC) coupled with high-resolution mass spectrometry (HRMS) and chemometric analyses. Principal component analysis (PCA) of all samples indicated no clear separation between SCH and C groups but indicated clear gender separation in the C group. Multivariate statistical analyses (PCA and orthogonal partial least squares discriminant analysis (OPLS-DA)) of gender-differentiated SCH and C groups established forty-nine differential lipids in the differentiation of male SCH (SCH-M) patients and male controls (C-M), while sixty putative biomarkers were identified in the differentiation of female SCH patients (SCH-F) and female controls (C-F). Lipidomic study of gender-differentiated groups, between SCH-M and C-M and between SCH-F and C-F groups, confirmed that lipids metabolism was altered and the content of the majority of the most affected lipid classes, glycerophospholipids (GP), sphingolipids (SP), glycerolipids (GL) and fatty acids (FA), was decreased compared to controls. From differential lipid metabolites with higher content in both SCH-M and SCH-F patients groups compared to their non-psychiatric controls, there were four common lipid molecules: ceramides Cer 34:2, and Cer 34:1, lysophosphatidylcholine LPC 16:0 and triacylglycerol TG 48:2. Significant alteration of lipids metabolism confirmed the importance of metabolic pathways in the pathogenesis of schizophrenia. [ABSTRACT FROM AUTHOR]

Background: Cancer cells exhibit remarkable metabolic plasticity, enabling them to adapt to fluctuating nutrient conditions. This study investigates the impact of a combination of low glucose levels and inhibition of stearoyl-CoA desaturase 1 (SCD1) using A939572 on cancer metabolic plasticity and growth. Methods: A comprehensive metabolomic and lipidomic analysis was conducted to unravel the intricate changes in cellular metabolites and lipids. MCF-7 cells were subjected to low glucose conditions, and SCD1 was inhibited using A939572. The resulting alterations in metabolic pathways and lipid profiles were explored to elucidate the synergistic effects on cancer cell physiology. Results: The combination of low glucose and A939572-induced SCD1 inhibition significantly impaired cancer cell metabolic plasticity. Metabolomic analysis highlighted shifts in key glycolytic and amino acid pathways, indicating the cells’ struggle to adapt to restricted glucose availability. Lipidomic profiling revealed alterations in lipid composition, implying disruptions in membrane integrity and signaling cascades. Conclusion: Our findings underscore the critical roles of glucose availability and SCD1 activity in sustaining cancer metabolic plasticity and growth. Simultaneously targeting these pathways emerges as a promising strategy to impede cancer progression. The comprehensive metabolomic and lipidomic analysis provides a detailed roadmap of molecular alterations induced by this combination treatment, that may help identify potential therapeutic targets. [ABSTRACT FROM AUTHOR]

Background: Sepsis is defined as a dysfunctional host response to infection. The diverse clinical presentations of sepsis pose diagnostic challenges and there is a demand for enhanced diagnostic markers for sepsis as well as an understanding of the underlying pathological mechanisms involved in sepsis. From this perspective, metabolomics has emerged as a potentially valuable tool for aiding in the early identification of sepsis that could highlight key metabolic pathways and underlying pathological mechanisms. Objective: The aim of this investigation is to explore the early metabolomic and lipidomic profiles in a prospective cohort where plasma samples (n = 138) were obtained during ambulance transport among patients with infection according to clinical judgement who subsequently developed sepsis, patients who developed non-septic infection, and symptomatic controls without an infection. Methods: Multiplatform metabolomics and lipidomics were performed using UHPLC–MS/MS and UHPLC–QTOFMS. Uni- and multivariable analysis were used to identify metabolite profiles in sepsis vs symptomatic control and sepsis vs non-septic infection. Results: Univariable analysis disclosed that out of the 457 annotated metabolites measured across three different platforms, 23 polar, 27 semipolar metabolites and 133 molecular lipids exhibited significant differences between patients who developed sepsis and symptomatic controls following correction for multiple testing. Furthermore, 84 metabolites remained significantly different between sepsis and symptomatic controls following adjustment for age, sex, and Charlson comorbidity score. Notably, no significant differences were identified in metabolites levels when comparing patients with sepsis and non-septic infection in univariable and multivariable analyses. Conclusion: Overall, we found that the metabolome, including the lipidome, was decreased in patients experiencing infection and sepsis, with no significant differences between the two conditions. This finding indicates that the observed metabolic profiles are shared between both infection and sepsis, rather than being exclusive to sepsis alone. [ABSTRACT FROM AUTHOR]

Background: Allergic diseases begin early in life and are often chronic, thus creating an inflammatory environment that may precede or exacerbate other pathologies. In this regard, allergy has been associated to metabolic disorders and with a higher risk of cardiovascular disease, but the underlying mechanisms remain incompletely understood. Methods: We used a murine model of allergy and atherosclerosis, different diets and sensitization methods, and cell‐depleting strategies to ascertain the contribution of acute and late phase inflammation to dyslipidemia. Untargeted lipidomic analyses were applied to define the lipid fingerprint of allergic inflammation at different phases of allergic pathology. Expression of genes related to lipid metabolism was assessed in liver and adipose tissue at different times post‐allergen challenge. Also, changes in serum triglycerides (TGs) were evaluated in a group of 59 patients ≥14 days after the onset of an allergic reaction. Results: We found that allergic inflammation induces a unique lipid signature that is characterized by increased serum TGs and changes in the expression of genes related to lipid metabolism in liver and adipose tissue. Alterations in blood TGs following an allergic reaction are independent of T‐cell‐driven late phase inflammation. On the contrary, the IgG‐mediated alternative pathway of anaphylaxis is sufficient to induce a TG increase and a unique lipid profile. Lastly, we demonstrated an increase in serum TGs in 59 patients after undergoing an allergic reaction. Conclusion: Overall, this study reveals that IgG‐mediated allergic inflammation regulates lipid metabolism. [ABSTRACT FROM AUTHOR]