Insights into the CD1 lipidome.

CD1 isoforms are MHC class I-like molecules that present lipid-antigens to T cells and have been associated with a variety of immune responses. The lipid repertoire bound and presented by the four CD1 isoforms may be influenced by factors such as the cellular lipidome, subcellular microenvironment, and the properties of the binding pocket. In this study, by shotgun mass spectrometry, we performed a comprehensive lipidomic analysis of soluble CD1 molecules. We identified 1040 lipids, of which 293 were present in all isoforms. Comparative analysis revealed that the isoforms bind almost any cellular lipid.CD1a and CD1c closely mirrored the cellular lipidome, while CD1b and CD1d showed a preference for sphingolipids. Each CD1 isoform was found to have unique lipid species, suggesting some distinct roles in lipid presentation and immune responses. These findings contribute to our understanding of the role of CD1 system in immunity and could have implications for the development of lipid-based therapeutics.

Novel metabolic and lipidomic biomarkers of sarcopenia.

BACKGROUND: The pathophysiology of sarcopenia is complex and multifactorial and has not been fully elucidated. The impact of resistance training and nutritional support (RTNS) on metabolomics and lipodomics in older adults with sarcopenia remains uncertain. This study aimed to explore potential biomarkers of sarcopenia and clinical indicators of RTNS in older sarcopenic adults. METHODS: Older individuals diagnosed with sarcopenia through routine health checkups at a community hospital were recruited for a 12-week randomized controlled trial focusing on RTNS. Plasma metabolomic and lipidomic profiles of 45 patients with sarcopenia and 47 matched controls were analysed using 1H-nuclear magnetic resonance (1H-NMR) and liquid chromatography-mass spectrometer (LC-MS). RESULTS: At baseline, the patient and control groups had similar age, sex, and height distribution. The patient group had significantly lower weight, BMI, grip strength, gait speed, skeletal muscle index, lean mass of both the upper and lower limbs, and lower limb bone mass. There was a significant difference in 12 metabolites between the control and patient groups. They are isoleucine (patient/control fold change [FC] = 0.86 ± 0.04, P = 0.0005), carnitine (FC = 1.05 ± 0.01, P = 0.0110), 1-methylhistamine/3-methylhistamine (FC = 1.24 ± 0.14, P = 0.0039), creatinine (FC = 0.71 ± 0.04, P < 0.0001), carnosine (FC = 0.71 ± 0.04, P = 0.0007), ureidopropionic acid (FC = 0.61 ± 0.10, P = 0.0107), uric acid (FC = 0.88 ± 0.03, P = 0.0083), PC (18:2/20:0) (FC = 0.69 ± 0.03, P = 0.0010), PC (20:2/18:0) (FC = 0.70 ± 0.06, P = 0.0014), PC (18:1/20:1) (FC = 0.74 ± 0.05, P = 0.0015), PI 32:1 (FC = 4.72 ± 0.17, P = 0.0006), and PI 34:3 (FC = 1.88 ± 0.13, P = 0.0003). Among them, carnitine, 1-methylhistamine/3-methylhistamine, creatinine, ureidopropionic acid, uric acid, PI 32:1, and PI 34:3 were first identified. Notably, PI 32:1 had highest diagnostic accuracy (0.938) for sarcopenia. 1-Methylhistamine/3-methylhistamine, carnosine, PC (18:2/20:0), PI 32:1, and PI 34:3 levels were not different from the control group after RTNS. These metabolites are involved in amino acid metabolism, lipid metabolism, and the PI3K-AKT/mTOR signalling pathway through the ingenuity pathway analysis. CONCLUSIONS: These findings provide information on metabolic changes, lipid perturbations, and the role of RTNS in patients with sarcopenia. They reveal new insights into its pathological mechanisms and potential therapies.

The impact of lipidome on five inflammatory skin diseases: a Mendelian randomization study.

OBJECTIVE: Two-sample Mendelian randomization (TSMR) was employed to examine the association between lipidome and five inflammatory skin diseases. METHOD: To evaluate the association between various molecular subtypes of lipidome and the risk of five inflammatory skin diseases, we analyzed a comprehensive GWAS dataset comprising 179 lipidome. The Two-Sample Mendelian Randomization (TSMR) method was employed to investigate causal relationships. Heterogeneity and pleiotropy were assessed using Cochran's Q test, MR-Egger intercept test, and MR-PRESSO global test. Additionally, a sensitivity analysis was conducted to evaluate the influence of individual single nucleotide polymorphisms on Mendelian Randomization study. RESULTS: Using 179 serum lipidome as exposures and five common inflammatory skin diseases as outcomes, we investigated their associations in this large-scale study. Our findings reveal significant impacts of glycerophospholipids, glycerolipids, and sphingomyelins on inflammatory skin diseases. Glycerophospholipids were protective against pemphigus but predominantly posed risks for other inflammatory skin diseases. Specifically, phosphatidylcholine (16:0_0:0) exhibited the most significant risk association with lichen planus (OR = 1.25, 95% CI 1.11-1.40, P < 0.001). Conversely, glycerolipids showed no effect on lichen planus but were protective against pemphigus while potentially posing risks for other conditions. Triacylglycerol (46:2) showed the most substantial risk association with vitiligo (OR = 1.99, 95% CI 1.35-2.93, P < 0.001). Furthermore, sphingomyelins had no effect on atopic dermatitis but posed potential risks for other inflammatory skin diseases. Sphingomyelin (d40:1) notably emerged as a significant risk factor for pemphigus (OR = 1.91, 95% CI 1.37-2.66, P < 0.001). CONCLUSIONS: This study has elucidated the potential harmful effects of glycerophospholipids, glycerolipids, and sphingomyelins on inflammatory skin diseases, while also providing valuable insights for future research into the pathophysiology, prevention and treatment of these conditions.

Mendelian randomization of plasma lipidome, inflammatory proteome and heart failure.

AIMS: Heart failure (HF) is a global health issue, with lipid metabolism and inflammation critically implicated in its progression. This study harnesses cutting-edge, expanded genetic information for lipid and inflammatory protein profiles, employing Mendelian randomization (MR) to uncover genetic risk factors for HF. METHODS: We assessed genetic susceptibility to HF across 179 lipidomes and 91 inflammatory proteins using instrumental variables (IVs) from recent genome-wide association studies (GWASs) and proteome-wide quantitative trait loci (pQTL) studies. GWASs involving 47 309 HF cases and 930 014 controls were obtained from the Heart Failure Molecular Epidemiology for Therapeutic Targets (HERMES) Consortium. Data on 179 lipids from 7174 individuals in a Finnish cohort and 91 inflammatory proteins from a European pQTL study involving 14 824 individuals are available in the HGRI-EBI catalogue. A two-sample MR approach evaluated the associations, and a two-step mediation analysis explored the mediation role of inflammatory proteins in the lipid-HF pathway. Sensitivity analyses, including MR-RAPS (robust adjusted profile score) and MR-Egger, ensured result robustness. RESULTS: Genetic IVs for 162 lipids and 74 inflammatory proteins were successfully identified. MR analysis revealed a genetic association between HF and 31 lipids. Among them, 18 lipids, including sterol ester (27:1/18:0), cholesterol, 9 phosphatidylcholines, phosphatidylinositol (16:0_20:4) and 6 triacylglycerols, were identified as HF risk factors [odds ratio (OR) = 1.037-1.368]. Cholesterol exhibited the most significant association with elevated HF risk [OR = 1.368, 95% confidence interval (CI) = 1.044-1.794, P = 0.023]. In the inflammatory proteome, leukaemia inhibitory factor receptor (OR = 0.841, 95% CI = 0.789-0.897, P = 1.08E-07), fibroblast growth factor 19 (OR = 0.905, 95% CI = 0.830-0.988, P = 0.025) and urokinase-type plasminogen activator (OR = 0.938, 95% CI = 0.886-0.994, P = 0.030) were causally negatively correlated with HF, whereas interleukin-20 receptor subunit alpha (OR = 1.333, 95% CI = 1.094-1.625, P = 0.004) was causally positively correlated with HF. Mediation analysis revealed leukaemia inhibitory factor receptor (mediation proportion: 23.5%-25.2%) and urokinase-type plasminogen activator (mediation proportion: 9.5%-10.7%) as intermediaries in the lipid-inflammation-HF pathway. No evidence of directional horizontal pleiotropy was observed (P > 0.05). CONCLUSIONS: This study identifies a genetic connection between certain lipids, particularly cholesterol, and HF, highlighting inflammatory proteins that influence HF risk and mediate this relationship, suggesting new therapeutic targets and insights into genetic drivers in HF.

Investigating the lipid profile of Anopheles stephensi mosquitoes across developmental life stages.

Holometabolous insects undergo a distinct transition in their development, tightly correlated with shifting feeding patterns from larval stages and some adult phases to non-feeding phases as pupae and during other adult phases. Furthermore, the intricate life cycle of mosquitoes involves a sequence of developmental stages influenced by aquatic and terrestrial factors, demanding precise energy resource orchestration. Lipids serve multifaceted roles, encompassing energy storage, membrane structure, and participation in signal transduction and molecular recognition processes. A significant gap in the current research landscape is the need for a comprehensive study exploring the lipid repertoire throughout the developmental stages of Anopheles stephensi mosquitoes. We undertook an analysis of the An. stephensi metabolome across all life stages. We hypothesized that An. stephensi mosquitoes will have unique lipid metabolite markers for each life stage. A specific extraction and LC-MS based lipidomic approach was used to test this hypothesis. Our findings demonstrated that our methods were successful, with lipids comprising 62.15 % of the analyzed metabolome. Additionally, phospholipids (PL), lysophospholipids (LPL), sphingomyelin (SM), and triglycerides (TG) were abundant and dynamic across all life stages. Interestingly, comparison between the L1 and L2 lipidome revealed a dominant pattern of specific TGs in decreased abundance between these two life stages. Lastly, 20-hydroxyecdysone (20E), was found to be present in similar abundance across all 4 larval stages. These data indicate that there may be lipid metabolome pathways serving unique roles during mosquito development that may be used to explore laboratory management of colonies, parasite resistance, and environmental adaptation.

Tafazzin deficiency causes substantial remodeling in the lipidome of a mouse model of Barth Syndrome cardiomyopathy.

Barth Syndrome (BTHS) is a rare X-linked disease, characterized clinically by cardiomyopathy, skeletal myopathy, neutropenia, and growth retardation. BTHS is caused by mutations in the phospholipid acyltransferase tafazzin (Gene: TAFAZZIN, TAZ). Tafazzin catalyzes the final step in the remodeling of cardiolipin (CL), a glycerophospholipid located in the inner mitochondrial membrane. As the phospholipid composition strongly determines membrane properties, correct biosynthesis of CL and other membrane lipids is essential for mitochondrial function. Mitochondria provide 95% of the energy demand in the heart, particularly due to their role in fatty acid oxidation. Alterations in lipid homeostasis in BTHS have an impact on mitochondrial membrane proteins and thereby contribute to cardiomyopathy. We analyzed a transgenic TAFAZZIN-knockdown (TAZ-KD) BTHS mouse model and determined the distribution of 193 individual lipid species in TAZ-KD and WT hearts at 10 and 50 weeks of age, using electrospray ionization tandem mass spectrometry (ESI-MS/MS). Our results revealed significant lipid composition differences between the TAZ-KD and WT groups, indicating genotype-dependent alterations in most analyzed lipid species. Significant changes in the myocardial lipidome were identified in both young animals without cardiomyopathy and older animals with heart failure. Notable alterations were found in phosphatidylcholine (PC), phosphatidylethanolamine (PE), lysophosphatidylethanolamine (LPE), lysophosphatidylcholine (LPC) and plasmalogen species. PC species with 2-4 double bonds were significantly increased, while polyunsaturated PC species showed a significant decrease in TAZ-KD mice. Furthermore, Linoleic acid (LA, 18:2) containing PC and PE species, as well as arachidonic acid (AA, 20:4) containing PE 38:4 species are increased in TAZ-KD. We found higher levels of AA containing LPE and PE-based plasmalogens (PE P-). Furthermore, we are the first to show significant changes in sphingomyelin (SM) and ceramide (Cer) lipid species Very long-chained SM species are accumulating in TAZ-KD hearts, whereas long-chained Cer and several hexosyl ceramides (HexCer) species accumulate only in 50-week-old TAZ-KD hearts These findings offer potential avenues for the diagnosis and treatment of BTHS, presenting new possibilities for therapeutic approaches.

Impact of omega-3 fatty acids on hypertriglyceridemia, lipidomics, and gut microbiome in patients with type 2 diabetes.

BACKGROUND: Fish oil (FO), a mixture of omega-3 fatty acids mainly comprising docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA), has been recommended for patients with type 2 diabetes (T2D) and hypertriglyceridemia. However, its effects on lipidomic profiles and gut microbiota and the factors influencing triglyceride (TG) reduction remain unclear. METHODS: We conducted a 12-week, randomized, double-blind, placebo-controlled trial in 309 Chinese patients with T2D with hypertriglyceridemia (ClinicalTrials.gov: NCT03120299). Participants were randomly assigned (1:1) to receive either 4 g FO or corn oil for 12 weeks. The primary outcome was changes in serum TGs and the lipidomic profile, and the secondary outcome included changes in the gut microbiome and other metabolic variables. FINDINGS: The FO group had significantly better TG reduction (mean [95% confidence interval (CI)]: -1.51 [-2.01, -1.01] mmol/L) compared to the corn oil group (-0.66 [-1.15, -0.16] mmol/L, p = 0.02). FO significantly altered the serum lipid profile by reducing low-unsaturated TG species and increasing those containing DHA or EPA. FO had minor effects on gut microbiota, while baseline microbial features predicted the TG response to FO better than phenotypic or lipidomic features, potentially mediated by specific lipid metabolites. A total of 9 lipid metabolites significantly mediated the link between 4 baseline microbial variables and the TG response to FO supplementation. CONCLUSIONS: Our findings demonstrate differential impacts of omega-3 fatty acids on lipidomic and microbial profiles in T2D and highlight the importance of baseline gut microbiota characteristics in predicting the TG-lowering efficacy of FO. FUNDING: This study was funded by the National Nature Science Foundation.

Genetic causal association between lipidomic profiles, inflammatory proteomics, and aortic stenosis: a Mendelian randomization investigation.

BACKGROUND: Aortic stenosis (AS) is a prevalent and serious valvular heart disease with a complex etiology involving genetic predispositions, lipid dysregulation, and inflammation. The specific roles of lipid and protein biomarkers in AS development are not fully elucidated. This study aimed to elucidate the causal relationships between lipidome, inflammatory proteins, and AS using Mendelian randomization (MR), identifying potential therapeutic targets. METHODS: Utilizing data from large-scale genome-wide association studies (GWAS) and genome-wide protein quantitative trait loci (pQTL) studies, we conducted MR analyses on 179 plasma lipidome and 91 inflammatory proteins to assess their causal associations with AS. Our approach included Inverse Variance Weighting (IVW), Wald ratio, and robust adjusted profile score (RAPS) analyses to refine these associations. MR-Egger regression was used to address directional horizontal pleiotropy. RESULTS: Our MR analysis showed that genetically predicted 50 lipids were associated with AS, including 38 as risk factors [(9 Sterol ester, 18 Phosphatidylcholine, 4 Phosphatidylethanolamine, 1 Phosphatidylinositol and 6 Triacylglycerol)] and 12 as protective. Sterol ester (27:1/17:1) emerged as the most significant risk factor with an odds ratio (OR) of 3.11. Additionally, two inflammatory proteins, fibroblast growth factor 19 (FGF19) (OR = 0.830, P = 0.015), and interleukin 6 (IL-6) (OR = 0.729, P = 1.79E-04) were significantly associated with reduced AS risk. However, a two-step MR analysis showed no significant mediated correlations between these proteins and the lipid-AS pathway. CONCLUSION: This study reveals complex lipid and protein interactions in AS, identifying potential molecular targets for therapy. These results go beyond traditional lipid profiling and significantly advance our genetic and molecular understanding of AS, highlighting potential pathways for intervention and prevention.

Male infertility risk and plasma lipidome: a Mendelian randomization study.

Background: In recent years, the decline in sperm quality in men has become a global trend. There is a close relationship between sperm quality and pregnancy outcome. There is a large body of literature supporting the role of plasma lipidome in male infertility, while the complex mechanisms between them and male infertility are still less clear. Systematic study of the causal relationship between plasma lipidome and MI can help to provide new therapeutic ideas and targets for male infertility. Methods: In this study, we used a two-sample Mendelian randomization analysis based on Genome-wide association studies pooled data of 179 causal relationships between plasma lipidome and male infertility. We used employed the inverse variance weighted method as the main analysis to assess causality between exposure and outcome, in addition to MR-Egger, Weighted median as complementary methods, and tests for multiplicity and heterogeneity. Results: We identified 13 plasma lipidome comprising 4 types of plasma lipidome that were associated with male infertility. Among these, 9 plasma lipidome were found to be protective factors, while 4 were risk factors. Notably, the largest proportion of these plasma lipidome were triglyceride types, with Sphingomyelin (d40:1) exhibiting the strongest association with male infertility. Conclusion: These findings contribute to the current better understanding of male infertility and provide new perspectives on the underlying etiology of male infertility as well as prevention and treatment strategies. In addition, clinical trial validation is needed to assess the potential of these plasma lipidome as biomarkers.

Gut microbiome and plasma lipidome analysis reveals a specific impact of Clostridioides difficile infection on intestinal bacterial communities and sterol metabolism.

Clostridioides difficile infection (CDI) causes alterations in the intestinal microbiota, frequently associated with changes in the gut metabolism of bile acids and cholesterol. In addition to the impact on microbiome composition and given the metabolic changes occurring during CDI, our work focuses on the importance to know the effects at the local and systemic levels, both during the infection and its treatment, by paying particular attention to plasma lipid metabolism due to its relationship with CDI pathogenesis. Specific changes, characterized by a loss of microbial richness and diversity and related to a reduction in short-chain acid-producing bacteria and an increase in bile salt hydrolase-producing bacteria, were observed in the gut microbiota of CDI patients, especially in those suffering from recurrent CDI (RCDI). However, gut microbiota showed its ability to restore itself after treatment, resembling healthy individuals, in those patients treated by fecal microbiome transfer (FMT), in contrast with those treated with antibiotics, and displaying increased levels of Eubacterium coprostanoligenes, a cholesterol-reducing anaerobe. Interestingly, changes in plasma lipidome revealed a global depletion in circulating lipids in CDI, with the largest impact on cholesteryl esters. CDI patients also showed a specific and consistent decrease in the levels of lipid species containing linoleic acid-an essential fatty acid-which were only partially recovered after antibiotic treatment. Analysis of the plasma lipidome reflects CDI impact on the gut microbiota and its metabolism, evidencing changes in sterol and fatty acid metabolism that are possibly related to specific alterations observed in gut microbial communities of CDI patients. IMPORTANCE: There is increasing evidence about the influence the changes in microbiota and its metabolism has on numerous diseases and infections such as Clostridioides difficile infection (CDI). The knowledge of these changes at local and systemic levels can help us manage this infection to avoid recurrences and apply the best therapies, such as fecal microbiota transfer (FMT). This study shows a better restoration of the gut in FMT-treated patients than in antibiotic-treated patients, resembling healthy controls and showing increased levels of cholesterol-reducing bacteria. Furthermore, it evidences the CDI impact on plasma lipidome. We observed in CDI patients a global depletion in circulating lipids, particularly cholesteryl esters, and a specific decrease in linoleic acid-containing lipids, an essential fatty acid. Our observations could impact CDI management because the lipid content was only partially recovered after treatment, suggesting that continued nutritional support, aiming to restore healthy lipid levels, could be essential for a full recovery.

The impact of sampling time point on the lipidome composition.

Lipidomic profiling has been reported as an effective approach for characterizing and differentiating brain tumors. However, since lipids can undergo non-specific enzymatic and nonenzymatic reactions due to tissue disruption, it is critical to consider the preanalytical phase of the diagnostic process (e.g., optimizing the sampling time and sampling conditions). Thus, this study assesses the ways in which the time point of sampling impacts the lipidome composition of brain tumors. Two histologically distinct brain tumors-namely, meningiomas and gliomas-were sampled using solid-phase microextraction (SPME) fibers at two time points: on-site directly after removal, and after 12 months of storage at -30 °C. The samples were analyzed via HILIC chromatography coupled with HRMS, which enabled the detection of a wide range of features, including phospholipids and sphingolipids, as well as changes in the profiles of these compounds. The samples obtained from the stored tissues tended to have elevated levels of analytes with lower m/z values. In addition, the samples obtained from the fresh and stored tissues were easily distinguished based on their lipidome compositions, regardless of the histological tumor type. Notably, while storage did not affect the possibility of differentiating meningiomas and gliomas, the biological interpretation of the obtained results were prone to bias.

Cold-induced phosphatidylethanolamine synthesis in liver and brown adipose tissue of mice.

Increasing energy expenditure in brown adipose (BAT) tissue by cold-induced lipolysis is discussed as a potential strategy to counteract imbalanced lipid homeostasis caused through unhealthy lifestyle and cardiometabolic disease. Yet, it is largely unclear how liberated fatty acids (FA) are metabolized. We investigated the liver and BAT lipidome of mice housed for 1 week at thermoneutrality, 23 °C and 4 °C using quantitative mass spectrometry-based lipidomics. Housing at temperatures below thermoneutrality triggered the generation of phosphatidylethanolamine (PE) in both tissues. Particularly, the concentrations of PE containing polyunsaturated fatty acids (PUFA) in their acyl chains like PE 18: 0_20:4 were increased at cold. Investigation of the plasma's FA profile using gas chromatography coupled to mass spectrometry revealed a negative correlation of PUFA with unsaturated PE in liver and BAT indicating a flux of FA from the circulation into these tissues. Beta-adrenergic stimulation elevated intracellular levels of PE 38:4 and PE 40:6 in beige wildtype adipocytes, but not in adipose triglyceride lipase (ATGL)-deficient cells. These results imply an induction of PE synthesis in liver, BAT and thermogenic adipocytes after activation of the beta-adrenergic signaling cascade.

Volatilome is Inflammasome- and Lipidome-Dependent in Ischemic Heart Disease.

Ischemic heart disease (IHD) is a pathology of global interest because it is widespread and has high morbidity and mortality. IHD pathophysiology involves local and systemic changes, including lipidomic, proteomic, and inflammasome changes in serum plasma. The modulation in these metabolites is viable in the pre-IHD, during the IHD period, and after management of IHD in all forms, including lifestyle changes and pharmacological and surgical interventions. Therefore, these biochemical markers (metabolite changes; lipidome, inflammasome, proteome) can be used for early prevention, treatment strategy, assessment of the patient's response to the treatment, diagnosis, and determination of prognosis. Lipidomic changes are associated with the severity of inflammation and disorder in the lipidome component, and correlation is related to disturbance of inflammasome components. Main inflammasome biomarkers that are associated with coronary artery disease progression include IL-1ß, Nucleotide-binding oligomerization domain-like receptor family pyrin domain containing 3 (NLRP3), and caspase-1. Meanwhile, the main lipidome biomarkers related to coronary artery disease development involve plasmalogen lipids, lysophosphatidylethanolamine (LPE), and phosphatidylethanolamine (PE). The hypothesis of this paper is that the changes in the volatile organic compounds associated with inflammasome and lipidome changes in patients with coronary artery disease are various and depend on the severity and risk factor for death from cardiovascular disease in the time span of 10 years. In this paper, we explore the potential origin and pathway in which the lipidome and or inflammasome molecules could be excreted in the exhaled air in the form of volatile organic compounds (VOCs).

The Effects of Pregestational Overweight and Obesity on Maternal Lipidome in Pregnancy: Implications for Newborns' Characteristics.

Obesity is an important risk factor for the development of pregnancy complications. We investigated the effects of pregestational overweight and obesity on maternal lipidome during pregnancy and on newborns' characteristics. The study encompassed 131 pregnant women, 99 with pre-pregnancy body mass index (BMI) < 25 kg/m2 and 32 with BMI ≥ 25 kg/m2. Maternal lipid status parameters, plasma markers of cholesterol synthesis and absorption and sphingolipids were determined in each trimester. Data on neonatal height, weight and APGAR scores were assessed. The results showed a higher prevalence (p < 0.05) of pregnancy and childbirth complications among the participants with elevated pregestational BMI. Levels of total cholesterol, HDL-cholesterol (p < 0.05) and LDL-cholesterol (p < 0.01) were significantly lower, and concentrations of triglycerides were higher (p < 0.05) in women with increased pre-gestational BMI. Lower concentrations of the cholesterol synthesis marker, desmosterol, in the 2nd trimester (p < 0.01) and the cholesterol absorption marker, campesterol, in each trimester (p < 0.01, p < 0.05, p < 0.01, respectively) were also found in this group. Markers of maternal cholesterol synthesis were in positive correlation with neonatal APGAR scores in the group of mothers with healthy pre-pregnancy weight but in negative correlation in the overweight/obese group. Our results indicate that gestational adaptations of maternal lipidome depend on her pregestational nutritional status and that such changes may affect neonatal outcomes.

Dynamics of the lipid body lipidome in the oleaginous yeast Yarrowia sp.

Time-dependent changes in the lipid body (LB) lipidome of two oleaginous yeasts, Yarrowia lipolytica NCIM 3589 and Yarrowia bubula NCIM 3590 differing in growth temperature was investigated. LB size and lipid content were higher in Y. lipolytica based on microscopy, Feret, and integrated density analysis with lipid accumulation and mobilization occurring at 48 h in both strains. Variations in LB lipidome were reflected in interfacial tension (59.67 and 68.59 mN m-1) and phase transition temperatures (30°C-100°C and 60°C-100°C) for Y. lipolytica and Y. bubula, respectively. Liquid Chromatography-Mass Spectroscopy (LC-MS) analysis revealed neutral lipids (NLs), phospholipids, sphingolipids, sterols, and fatty acids as the major classes present in both strains while fatty acid amides were seen only in Y. lipolytica. Amongst the lipid classes, a few species were present in abundance with a number of lipids being less dominant. Permutational multivariate analysis of variance (PERMANOVA) and Analysis of covariance (ANOCOVA) analysis suggest 22 lipids belonging to NLs, fatty acid amides, and free fatty acids were found to be statistically different between the two strains. Analysis of the ratios between different lipid components suggest changes in LB size and mobilization as a function of time. The results indicate influence of temperature and strain variation on the dynamics of LB lipidome in Yarrowia species.

Long-term impacts of egg quiescence and Wolbachia infection on lipid profiles in Aedes aegypti: Ovarian roles in lipid synthesis during reproduction.

Wolbachia, an endosymbiotic bacterium, relies on nutrients from its host to complete its life cycle. The presence of Wolbachia strain wAlbB in the mosquito Aedes aegypti during egg or larval stages affects the host's development, leading to the absence of developed and visible ovaries in adult mosquito females. In this study, we investigated the impacts of egg quiescence and Wolbachia infection on lipid profiles of adult Ae. aegypti females, and discerned the role of ovaries in lipid synthesis in the reproductive process. The lipidomes of Wolbachia infected and uninfected female individuals at various developmental stages were quantitatively analyzed by LC-MS/MS. Lipidomic change patterns were systematically further investigated in wAlbB-infected fertile females and infertile females following blood feeding. Prolonged egg quiescence induced a shortage of acyl-carnitine (CAR) and potentially impacted some molecules of diacyl-phospholipid (diacyl-PL) and sphingolipid (SL) in young adult mosquitoes. After the first gonotrophic cycle, infertile females accumulated more CAR and lyso-phospholipid (lyso-PL) than fertile females. Then in the second gonotrophic cycle, the patterns of different lipid groups remained similar between fertile and infertile females. Only a small proportion of molecules of triglyceride (TG), phospholipid (lyso-PL and diacyl-PL) and ceramide (Cer) increased exclusively in fertile females from 0 h to 16 h post blood meal, suggesting that the generation or prescence of these lipids rely on ovaries. In addition, we found cardiolipins (CL) might be impacted by Wolbachia infection at the egg stage, and infected mosquitoes also showed distinct patterns between fertile and infertile females at their second gonotrophic cycle. Our study provides new insights into the long-term influence of Wolbachia on lipid profiles throughout various life stages of mosquitoes. Additionally, it suggests a role played by ovaries in lipid synthesis during mosquito reproduction.

Comprehensive Lipidomic Analysis of Three Edible Microalgae Species Based on RPLC-Q-TOF-MS/MS.

Microalgae, integral to marine ecosystems for their rich nutrient content, notably lipids and proteins, were investigated by using reversed-phase liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (RPLC-Q-TOF-MS/MS). This study focused on lipid composition in three commonly used microalgae species (Spirulina platensis, Chlorella vulgaris, and Schizochytrium limacinum) for functional food applications. The analysis unveiled more than 700 lipid molecular species, including glycolipids (GLs), phospholipids (PLs), sphingolipids (SLs), glycerolipids, and betaine lipids (BLs). GLs (19.9-64.8%) and glycerolipids (24.1-70.4%) comprised the primary lipid. Some novel lipid content, such as acylated monogalactosyldiacylglycerols (acMGDG) and acylated digalactosyldiacylglycerols (acDGDG), ranged from 0.62 to 9.68%. The analysis revealed substantial GLs, PLs, and glycerolipid variations across microalgae species. Notably, S. platensis and C. vulgaris displayed a predominance of fatty acid (FA) 18:2 and FA 18:3 in GLs, while S. limacinum exhibited a prevalence of FA 16:0, collectively constituting over 60% of the FAs of GLs. In terms of PLs and glycerolipids, S. platensis and C. vulgaris displayed elevated levels of arachidonic acid (AA) and eicosapentaenoic acid (EPA), whereas S. limacinum exhibited a significant presence of docosahexaenoic acid (DHA). Principal component analysis (PCA) revealed MGDG (16:0/18:1), DG (16:0/22:5), Cer (d18:1/20:0), and LPC (16:1) as promising lipid markers for discriminating between these microalgae samples. This study contributes to a comprehensive understanding of lipid profiles in three microalgae species, emphasizing their distinct biochemical characteristics and potentially informing us of their high-value utilization in the food industry.

Multi-scale signaling and tumor evolution in high-grade gliomas.

Although genomic anomalies in glioblastoma (GBM) have been well studied for over a decade, its 5-year survival rate remains lower than 5%. We seek to expand the molecular landscape of high-grade glioma, composed of IDH-wildtype GBM and IDH-mutant grade 4 astrocytoma, by integrating proteomic, metabolomic, lipidomic, and post-translational modifications (PTMs) with genomic and transcriptomic measurements to uncover multi-scale regulatory interactions governing tumor development and evolution. Applying 14 proteogenomic and metabolomic platforms to 228 tumors (212 GBM and 16 grade 4 IDH-mutant astrocytoma), including 28 at recurrence, plus 18 normal brain samples and 14 brain metastases as comparators, reveals heterogeneous upstream alterations converging on common downstream events at the proteomic and metabolomic levels and changes in protein-protein interactions and glycosylation site occupancy at recurrence. Recurrent genetic alterations and phosphorylation events on PTPN11 map to important regulatory domains in three dimensions, suggesting a central role for PTPN11 signaling across high-grade gliomas.

Comparative Transcriptomic and Lipidomic Analysis of Fatty Acid Accumulation in Three Camellia oleifera Varieties During Seed Maturing.

Camellia oleifera, a major woody oil crop in China, produces tea oil rich in unsaturated fatty acids, earning it names like liquid gold and eastern olive oil. This study provides an integrated investigation of the transcriptome and lipidome within seeds at the maturing process across three C. oleifera varieties, revealing a significant relationship between fatty acid production and genes involved in lipid synthesis. Through transcriptomic analysis, 26,344 genes with varied expression were found. Functional enrichment analysis highlighted that pathways related to starch and sucrose metabolism, plant hormone signal transduction, and lipid accumulation were highly enriched among the differentially expressed genes. Coordinated high expression of key genes (ACCase, KAS I, KAS II, KAS III, KAR, HAD, EAR, SAD, LPAAT, LACS, DGAT, PDAT) during the late maturation stage contributes largely to high oil content. Additionally, expression variations of SAD and FADs among different varieties were explored. The analysis suggests that high expression of genes such as FAD3, FAD7, and FAD8 notably increased linolenic acid content. This research provides new insights into the molecular mechanisms of oil biosynthesis in C. oleifera, offering valuable references for improving yield and quality.

Temperature change elicits lipidome adaptation in the simple organisms Mycoplasma mycoides and JCVI-syn3B.

Cell membranes mediate interactions between life and its environment, with lipids determining their properties. Understanding how cells adjust their lipidomes to tune membrane properties is crucial yet poorly defined due to the complexity of most organisms. We used quantitative shotgun lipidomics to study temperature adaptation in the simple organism Mycoplasma mycoides and the minimal cell JCVI-syn3B. We show that lipid abundances follow a universal logarithmic distribution across eukaryotes and bacteria, with comparable degrees of lipid remodeling for adaptation regardless of lipidomic or organismal complexity. Lipid features analysis demonstrates head-group-specific acyl chain remodeling as characteristic of lipidome adaptation; its deficiency in Syn3B is associated with impaired homeoviscous adaptation. Temporal analysis reveals a two-stage cold adaptation process: swift cholesterol and cardiolipin shifts followed by gradual acyl chain modifications. This work provides an in-depth analysis of lipidome adaptation in minimal cells, laying a foundation to probe the design principles of living membranes.