Search Results (29)

Abnormalities in plasma lipoproteins observed in patients with diabetes promote atherosclerosis. However, the association between various lipid species and classes and atherosclerosis remains unclear. Here, we aimed to identify the plasma lipid characteristics associated with atherosclerosis progression in patients with diabetes. We performed semi-targeted lipidomic analysis of fasting plasma samples using supercritical fluid chromatography coupled with mass spectrometry in two independent patient groups with type 2 diabetes (n = 223 and 31) and evaluated cross-sectional associations between plasma lipids and carotid intima-media thickness (CIMT). Ten plasma lipid species, including eight diacylglycerols (DGs), and total DG levels were significantly associated with CIMT in both groups. Patients of the former group were partly observed for 5 years, and we investigated associations between DGs and CIMT progression in these patients (n = 101). As a result, 22 DGs among the 26 identified DGs and total DG (β = 0.398, p < 0.001) were significantly associated with the annual change in CIMT. Furthermore, plasma DG levels improved the predictive ability for CIMT progression, with an adjusted R-squared increase of 0.105 [95% confidence interval: 0.010, 0.232] in the models. Plasma DGs are associated with CIMT progression in patients with type 2 diabetes. Measurement of total plasma DG levels may be beneficial in assessing the risk of atherosclerosis progression. Full article

Lard imparts unique organoleptic properties that underpin its essential role in Chinese gastronomy; however, the specific lipid precursors contributing to its aroma remain unclear. This study explores the flavor formation mechanism of lard by comparing its texture and aroma at two preparation temperatures, 130 °C and 100 °C. We identified a total of 256 and 253 lipids at these temperatures, respectively, with triacylglycerols (TGs) and diacylglycerols (DGs) being the predominant lipid species. An HS-GC-IMS analysis detected 67 volatile compounds, predominantly aldehydes, acids, and alcohols. A subsequent Orthogonal Partial Least Squares-Discriminant Analysis (OPLS-DA) identified 49 discriminatory lipids and 20 differential volatiles. A correlation analysis showed a positive relationship between aldehydes and unsaturated triglycerides in lard, with TG (16:1-16:1-18:0), TG (17:2-18:1-18:1), TG (16:1-17:1-18:1), and TG (18:1-18:1-20:1) identified as characteristic markers at both temperatures. Furthermore, there was a positive correlation between ketones and alcohols and phospholipids and sphingolipids containing unsaturated fatty acid chains. TGs and glycerophospholipids (GPs), rich in polyunsaturated fatty acids, are likely key precursors driving the formation of distinct flavors during lard processing. This study elucidates the mechanistic interactions between lipids and volatile organic compounds, providing a framework for optimizing lard processing protocols and flavor modulation. Full article

Background/Objectives: Abnormal brain glycerolipid metabolism has been reported for Alzheimer’s disease (AD). This includes both diacylglycerols (DGs) and monogalactosyl-DGs (MGDGs), which are elevated in AD subjects. While DGs are also elevated in subjects with mild cognitive impairment (MCI), MGDGs have not yet been examined at this early stage of cognitive impairment. Methods: MGDG, triacylglycerol (TG), and ether glycerolipid levels in the cerebral cortex gray matter of controls, MCI, and non-demented Alzheimer’s neuropathology (NDAN) subjects were monitored by high-resolution mass spectrometry (<2 ppm mass error). Results: MGDG, MGDG ether, DG ether, and TG levels were elevated in the cerebral cortex of MCI but not NDAN subjects. Conclusions: A diverse array of glycerolipids was elevated in MCI subjects, suggesting a role in cognitive dysfunction. This suggestion is further supported by the maintenance of normal glycerolipid levels in NDAN subjects with amyloid accumulation but not cognitive deficits. Our data clearly indicate that while complex lipid alterations occur in MCI subjects, relative to controls 20 years younger, no such lipid alterations occur in NDAN subjects. While amyloid deposition in MCI is not involved in the observed lipid alterations, other ongoing neuropathologies may contribute to changes in lipid dynamics and vice versa. Full article

The success of assisted reproductive technology is contingent upon the growth potential of embryos post-vitrification process. When compared to in vivo embryos, it has been found that the high intracellular lipid accumulation inside the in vitro-derived embryos results in poor survival during vitrification. Based on this finding, the present study assessed the impact of incorporating forskolin and linoleic acid (FL) entering in vitro culture (IVC) on the embryos’ cryo-survival, lipid content, and viability throughout vitrification. Lipid metabolomics and single-cell RNA sequencing (scRNA-seq) techniques were used to determine the underlying mechanism that the therapies were mimicking. It was observed that out of 726 identified lipids, 26 were expressed differentially between the control and FL groups, with 12 lipids upregulated and 14 lipids downregulated. These lipids were classified as Triacylglycerol (TG), Diacylglycerol (DG), Phosphatidylcholine (PC), and so on. A total of 1079 DEGs were detected between the FL and control groups, consisting of 644 upregulated genes and 435 downregulated genes. These DEGs were significantly enhanced in the arachidonic acid metabolism, lipolysis, fatty acid metabolism, cAMP signaling pathway, and other critical developmental pathways. Based on the observation, it was concluded that forskolin and linoleic acid decreased the droplet content of embryos by modulating lipid metabolism, thus enhancing the vitrified bovine embryos’ cryo-survival. Full article

Little is known about lipid changes that occur in the setting of metabolic-dysfunction-associated steatotic liver disease (MASLD) regression. We previously reported improvements in hepatic steatosis, de novo lipogenesis (DNL), and metabolomic profiles associated with oxidative stress, inflammation, and selected lipid metabolism in 40 adolescent boys (11–16 y) with hepatic steatosis ≥5% (98% meeting the definition of MASLD). Participants were randomized to a low-free-sugar diet (LFSD) (n = 20) or usual diet (n = 20) for 8 weeks. Here, we employed untargeted/targeted lipidomics to examine lipid adaptations associated with the LFSD and improvement of hepatic steatosis. Our LC-MS/MS analysis revealed decreased triglycerides (TGs), diacylglycerols (DGs), cholesteryl esters (ChE), lysophosphatidylcholine (LPC), and phosphatidylcholine (PC) species with the diet intervention (p < 0.05). Network analysis demonstrated significantly lower levels of palmitate-enriched TG species post-intervention, mirroring the previously shown reduction in DNL in response to the LFSD. Targeted oxylipins analysis revealed a decrease in the abundance of 8-isoprostane and 14,15-DiHET and an increase in 8,9-DiHET (p < 0.05). Overall, we observed reductions in TGs, DGs, ChE, PC, and LPC species among participants in the LFSD group. These same lipids have been associated with MASLD progression; therefore, our findings may indicate normalization of key biological processes, including lipid metabolism, insulin resistance, and lipotoxicity. Additionally, our targeted oxylipins assay revealed novel changes in eicosanoids, suggesting improvements in oxidative stress. Future studies are needed to elucidate the mechanisms of these findings and prospects of these lipids as biomarkers of MASLD regression. Full article

Ectopic fat accumulation in non-adipose tissues is closely related to diabetes-related myocardial dysfunction. Nevertheless, the complete picture of the lipid metabolites involved in the metabolic-related myocardial alterations is not fully characterized. The aim of this study was to characterize the specific lipid profile in hearts in an animal model of obesity/insulin resistance induced by a high-fat diet (HFD). The cardiac lipidome profiles were assessed via liquid chromatography–mass spectrometry (LC–MS)/MS-MS and laser desorption/ionization–mass spectrometry (LDI–MS) tissue imaging in hearts from C57BL/6J mice fed with an HFD or standard-diet (STD) for 12 weeks. Targeted lipidome analysis identified a total of 63 lipids (i.e., 48 triacylglycerols (TG), 5 diacylglycerols (DG), 1 sphingomyelin (SM), 3 phosphatidylcholines (PC), 1 DihydroPC, and 5 carnitines) modified in hearts from HFD-fed mice compared to animals fed with STD. Whereas most of the TG were up-regulated in hearts from animals fed with an HFD, most of the carnitines were down-regulated, thereby suggesting a reduction in the mitochondrial β-oxidation. Roughly 30% of the identified metabolites were oxidated, pointing to an increase in lipid peroxidation. Cardiac lipidome was associated with a specific biochemical profile and a specific liver TG pattern. Overall, our study reveals a specific cardiac lipid fingerprint associated with metabolic alterations induced by HFD. Full article

Type 2 diabetes mellitus (T2DM) poses a higher risk for complications in South Asian individuals compared to other ethnic groups. To shed light on potential mediating factors, we investigated lipidomic changes in plasma of Dutch South Asians (DSA) and Dutch white Caucasians (DwC) with and without T2DM and explore their associations with clinical features. Using a targeted quantitative lipidomics platform, monitoring over 1000 lipids across 17 classes, along with ¹H NMR based lipoprotein analysis, we studied 51 healthy participants (21 DSA, 30 DwC) and 92 T2DM patients (47 DSA, 45 DwC) from the MAGNetic resonance Assessment of VICTOza efficacy in the Regression of cardiovascular dysfunction in type 2 dIAbetes mellitus (MAGNA VICTORIA) study. This comprehensive mapping of the circulating lipidome allowed us to identify relevant lipid modules through unbiased weighted correlation network analysis, as well as disease and ethnicity related key mediatory lipids. Significant differences in lipidomic profiles, encompassing various lipid classes and species, were observed between T2DM patients and healthy controls in both the DSA and DwC populations. Our analyses revealed that healthy DSA, but not DwC, controls already exhibited a lipid profile prone to develop T2DM. Particularly, in DSA-T2DM patients, specific lipid changes correlated with clinical features, particularly diacylglycerols (DGs), showing significant associations with glycemic control and renal function. Our findings highlight an ethnic distinction in lipid modules influencing clinical outcomes in renal health. We discover distinctive ethnic disparities of the circulating lipidome and identify ethnicity-specific lipid markers. Jointly, our discoveries show great potential as personalized biomarkers for the assessment of glycemic control and renal function in DSA-T2DM individuals. Full article

Time-of-Flight–Secondary Ion Mass Spectrometry (ToF-SIMS) using a bismuth liquid metal ion source was utilized to characterize and image microbial biomarkers within dolomite from early-middle Miocene coastal mud volcano outcrops in Kuwait. ToF-SIMS analysis revealed biomarkers of ancient microbial consortia of sulfate reducers and methane oxidizers participating in the anaerobic oxidation of methane. The identified lipid biomarkers comprised 17α(H),21β(H)-Norhopane, Hop-17(21)-ene or Hop-22(29)-ene (diploptene), non-isoprenoidal dialkyl glycerol diethers (DAGEs), and Diacylglycerol esters (DGs). The ion µ-scale images of carbonate rocks showed two characteristic styles: (1) high signal intensity of dolomite, halite, and biomarkers, where the biomarkers demonstrate a distinctive co-localization pattern with both dolomite and halite; and (2) a lack of dolomite, halite low signal intensity, and an absence of biomarker co-localization patterns. Our results highlight three remarkable observations. Firstly, the concomitance of dolomite and halite suggests a common source of magnesium and sodium supply, likely from the hypersaline Al-Subiya sabkha. This emphasizes the importance of hypersaline seawater for dolomite formation. Secondly, microbial biomarkers correspond to methane- and sulfate-rich conditions under which dolomite was formed. Lastly, the high intensity of biomarker signals and their association with dolomite and halite indicate that the consortia involved in dolomite formation have preferences for high-salinity conditions. The three observations align with previous studies that have highlighted the importance of methane-sulfate redox, high salinity, and halophilic microbes for dolomite formation. This work is the first to acknowledge ancient microbial biomarkers within Miocene dolomite in Kuwait, which aims to broaden the understanding of the biogeochemical processes triggering dolomite formation in similar environments and ancient geologic settings. Full article

In this work, an investigation using UHPLC-Q-Orbitrap-MS and multivariate statistics was conducted to obtain the lipid fingerprint of Camembert cheese and to explore its correlated variation with respect to X-ray irradiation treatment. A total of 479 lipids, categorized into 16 different lipid subclasses, were measured. Furthermore, the identification of oxidized lipids was carried out to better understand the possible phenomena of lipid oxidation related to this technological process. The results confirm that the lipidomic approach adopted is effective in implementing the knowledge of the effects of X-ray irradiation on food and evaluating its safety aspects. Furthermore, Partial Least Squares-Discriminant Analysis (PLS-DA) and Linear Discriminant Analysis (LDA) were applied showing high discriminating ability with excellent values of accuracy, specificity and sensitivity. Through the PLS-DA and LDA models, it was possible to select 40 and 24 lipids, respectively, including 3 ceramides (Cer), 1 hexosyl ceramide (HexCer), 1 lysophosphatidylcholine (LPC), 1 lysophosphatidylethanolamine (LPE), 3 phosphatidic acids (PA), 4 phosphatidylcholines (PC), 10 phosphatidylethanolamines (PE), 5 phosphatidylinositols (PI), 2 phosphatidylserines (PS), 3 diacylglycerols (DG) and 9 oxidized triacylglycerols (OxTG) as potential markers of treatment useful in food safety control plans. Full article

Xylanase supplementation of diets is used to enhance nutrient digestibility in monogastrics which lack necessary enzymes for non-starch polysaccharide degradation. The effects of enzymatic treatment in the nutritional value of the feed are typically not comprehensively studied. Though the fundamental effects of xylanase on performance are well studied, limited data is available on the complex interactions between xylanase supplementation and hen physiology; therefore, the aim of this study was to develop a new, simple UPLC-TOF/MS lipidomics method for the analysis of hen egg yolks after supplementation with different amounts of xylanase. Sample preparation for the extraction of lipids was optimized and different sample preparation modes and solvent mixtures were tested. Optimal results for the extraction of total lipids were obtained by using the solvent mixture MTBE: MeOH (5:1, v/v). Multivariate statistical analysis of the signals of hundreds of lipids in positive and negative ionisation modes highlighted differences in several egg yolk lipid species-classes. Four lipid species-classes, phosphatidylcholines (PC and PC O), phosphatidylethanolamines (PE and PE O), phosphatidylinositols (PI), and fatty acids (FA), were among those contributing to the separation of the experimental groups (control-treated) in negative ionisation mode. In positive ionisation mode, principal beneficial lipid compounds such as phosphatidylcholines (PC and PC O), phosphatidylethanolamines (PE and PE O), triacylglycerols (TG), diacylglycerols (DG), and ceramides (Cer) were found to be increased in treated groups. Overall, supplementation of laying hens’ diets with xylanase significantly changed the lipid profile of egg yolks compared to the control diet. The association between the lipid profiles of egg yolks and hens’ diets, as well as the underlying mechanisms, require further investigation. These findings are of practical significance for the food industry. Full article

Obesity is an epidemic all around the world. Weight loss interventions that are effective differ from each other with regard to various lipidomic responses. Here, we aimed to find lipidomic biomarkers that are related to beneficial changes in weight loss. We adopted an untargeted liquid chromatography with tandem mass spectrometry (LC-MS/MS) method to measure 953 lipid species for Exercise (exercise intervention cohort, N = 25), 1388 lipid species for LSG (laparoscopic sleeve gastrectomy cohort, N = 36), and 886 lipid species for Cushing (surgical removal of the ACTH-secreting pituitary adenomas cohort, N = 25). Overall, the total diacylglycerol (DG), triacylglycerol (TG), phosphatidylethanolamine (PE), phosphatidylinositol (PI), phosphatidylserine (PS), and sphingomyelin (SM) levels were associated with changes in BMI, glycated hemoglobin (HbA1c), triglyceride, and total cholesterol according to weight loss interventions. We found that 73 lipid species changed among the three weight loss interventions. We screened 13 lipid species with better predictive accuracy in diagnosing weight loss situations in either Exercise, LSG, or Cushing cohorts (AUROC > 0.7). More importantly, we identified three phosphatidylcholine (PC) lipid species, PC (14:0_18:3), PC (31:1), and PC (32:2) that were significantly associated with weight change in three studies. Our results highlight potential lipidomic biomarkers that, in the future, could be used in personalized approaches involving weight loss interventions. Full article

Nobiletin (NOB) is a naturally occurring compound, commonly found in citrus peel, that shows hepatoprotective and lipid-reducing effects. However, the lipid biomarkers and the potential improvement mechanisms have not been adequately explored. Therefore, we investigated the ameliorative effect and the molecular mechanism of NOB on NAFLD induced by a high-fat diet in mice. The results showed that supplementation with NOB over 12 weeks markedly improved glucose tolerance, serum lipid profiles, inflammatory factors, hepatic steatosis, and oxidative stress. These beneficial effects were mainly related to reduced levels of potential lipid biomarkers including free fatty acids, diacylglycerols, triacylglycerols, and cholesteryl esters according to hepatic lipidomic analysis. Twenty lipids, including DGs and phosphatidylcholines, were identified as potential lipid biomarkers. Furthermore, RT-qPCR and Western blot analysis indicated that NOB inhibited the expression of lipogenesis-related factors such as SREBP-1c, SCD-1, and FAS, and upregulated the expression of lipid oxidation (PPARα) and cholesterol conversion (LXRα, CYP7A1, and CYP27A1) genes as well as antioxidation-related factors (Nucl-Nrf2, NQO1, HO-1, and GCLC), indicating that NOB intake may reduce lipid biosynthesis and increase lipid consumption to improve hepatic steatosis and oxidative stress. This study is beneficial for understanding the ameliorative effects of NOB on NAFLD. Full article

Triacylglycerol (TG) biosynthesis is an important metabolic process for intracellular storage of surplus energy, intestinal dietary fat absorption, attenuation of lipotoxicity, lipid transportation, lactation and signal transduction in mammals. Transmembrane protein 68 (TMEM68) is an endoplasmic reticulum (ER)-anchored acyltransferase family member of unknown function. In the current study we show that overexpression of TMEM68 promotes TG accumulation and lipid droplet (LD) formation in a conserved active sites-dependent manner. Quantitative targeted lipidomic analysis showed that diacylglycerol (DG), free fatty acid (FFA) and TG levels were increased by TMEM68 expression. In addition, TMEM68 overexpression affected the levels of several glycerophospholipids, such as phosphatidylcholine, phosphatidylethanolamine and phosphatidylinositol, as well as sterol ester contents. TMEM68 exhibited monoacylglycerol acyltransferase (MGAT) and diacylglycerol acyltransferase (DGAT) activities dependent on the conserved active sites in an in vitro assay. The expression of lipogenesis genes, including DGATs, fatty acid synthesis-related genes and peroxisome proliferator-activated receptor γ was upregulated in TMEM68-overexpressing cells. These results together demonstrate for the first time that TMEM68 functions as an acyltransferase and affects lipogenic gene expression, glycerolipid metabolism and TG storage in mammalian cells. Full article

Fat deposition traits are influenced by genetics and environment, which affect meat quality, growth rate, and energy metabolism of domestic animals. However, at present, the molecular mechanism of fat deposition is not entirely understood in beef cattle. Therefore, the current study conducted transcriptomics and lipid metabolomics analysis of subcutaneous, visceral, and abdominal adipose tissue (SAT, VAT, and AAT) of Huaxi cattle to investigate the differences among these adipose tissues and systematically explore how candidate genes interact with metabolites to affect fat deposition. These results demonstrated that compared with SAT, the gene expression patterns and metabolite contents of VAT and AAT were more consistent. Particularly, SCD expression, monounsaturated fatty acid (MUFA) and triglyceride (TG) content were higher in SAT, whereas PCK1 expression and the contents of saturated fatty acid (SFA), diacylglycerol (DG), and lysoglycerophosphocholine (LPC) were higher in VAT. Notably, in contrast to PCK1, 10 candidates including SCD, ELOVL6, ACACA, and FABP7 were identified to affect fat deposition through positively regulating MUFA and TG, and negatively regulating SFA, DG, and LPC. These findings uncovered novel gene resources and offered a theoretical basis for future investigation of fat deposition in beef cattle. Full article

Carotid atherosclerosis represents a relevant healthcare problem, since unstable plaques are responsible for approximately 15% of neurologic events, namely transient ischemic attack and stroke. Although statins treatment has proven effective in reducing LDL-cholesterol and the onset of acute clinical events, a residual risk may persist suggesting the need for the detection of reliable molecular markers useful for the identification of patients at higher risk regardless of optimal medical therapy. In this regard, several lines of evidence show a relationship among specific biologically active plasma lipids, atherosclerosis, and acute clinical events. We performed a Selected Reaction Monitoring-based High Performance Liquid Chromatography-tandem Mass Spectrometry (SRM-based HPLC-MS/MS) analysis on plasma HDL, LDL, and VLDL fractions purified, by isopycnic salt gradient ultracentrifugation, from twenty-eight patients undergoing carotid endarterectomy, having either a “hard” or a “soft” plaque, with the aim of characterizing the specific lipidomic patterns associated with features of carotid plaque instability. One hundred and thirty lipid species encompassing different lipid (sub)classes were monitored. Supervised multivariate analysis showed that lipids belonging to phosphatidylethanolamine (PE), sphingomyelin (SM), and diacylglycerol (DG) classes mostly contribute to discrimination within each lipoprotein fraction according to the plaque typology. Differential analysis evidenced a significant dysregulation of LDL PE (38:6), SM (32:1), and SM (32:2) between the two groups of patients (adj. p-value threshold = 0.05 and log₂FC ≥ |0.58|). Using this approach, some LDL-associated markers of plaque vulnerability have been identified, in line with the current knowledge of the key roles of these phospholipids in lipoprotein metabolism and cardiovascular disease. This proof-of-concept study reports promising results, showing that lipoprotein lipidomics may present a valuable approach for identifying new biomarkers of potential clinical relevance. Full article