Lipidomic Analysis Research Articles

Insights into the molecular mechanisms of lipid metabolism of air-dried goose on the formation of flavor substances by co-inoculation of lactic acid bacteria and staphylococcus based on GC-MS and lipidomics

Microorganisms and lipids always interact in a complex way in the meat matrix, which affects the flavor of meat products. This study aimed to examine the impact of complex fermentation with distinct microorganisms on fat oxidation, lipid profile, and the biochemical pathways involved in flavor substance formation. GC–MS analysis revealed that 12 key volatile substances including hexanal, heptanal, benzeneacetaldehyde, decanal, 1-nonanol, 1-hexanol, 1-octen-3-ol were responsible for the flavor variations in geese. Lipidomics analysis of three groups identified 440 lipid molecules, with triglycerides and glycerophospholipids being the most abundant categories. Spearman correlation analysis showed that 4 key volatile substances exhibited positive correlations with lysophosphatidylethanolamines, lysophosphatidycholines, phosphatidylcholines, phosphatidylethanolamines. The data presented herein facilitate an understanding of the lipid dynamics during fermentation and provide insights into the potential for controlling the flavor quality of fermented air-dried meat products.

Dietary nicotinamide improves growth performance and ameliorates liver lipid profiles by alleviating glycerophospholipid and sphingolipids metabolism in swamp eel (Monopterus albus)

The effect of dietary niacinamide (NAM) on the growth performance and liver lipid metabolism of swamp eel have been poorly investigated. Therefore, a 120-day feeding trial was conducted to provide different levels of NAM in diet and an untargeted lipidome analysis was performed to address this subject. We found that dietary NAM improved the growth performance of swamp eel. It also decreased the contents of glucose and lipids, including glucose, glycogen, TG, and NEFA, as well as fat accumulation in liver, but increased HDL-C content. We speculated that NAM inhibited lipid accumulation in liver by decreasing the key enzyme activity of LPL, HL and LPS. Fatty acid profile analysis showed that the contents of MUFA and PUFA, such as palmitoleic acid, oleic acid, and eicosapentaenoic acid were significantly increased, while the contents of SFA, such as myristic acid, stearic acid, and palmitic acid were decreased in liver by dietary NAM. Lipidome analysis also indicated that the majority of differential lipid metabolites belonged to glycerophospholipids and sphingolipids, which were enriched in the pathways of insulin resistance, adipocytokine signaling pathway, cholesterol metabolism, fat digestion and absorption, lipid and atherosclerosis, and lipid cell lipolysis regulation. These findings gave scientific evidences and novel insights into the metabolic responses to dietary NAM in swamp eel, and provided basic knowledge for using NAM as a feed additive in swamp eel production.

A specific serum lipid signature characterizes patients with glycogen storage disease type Ia

Glycogen storage disease type Ia (GSDIa) is a rare, inherited glucose-6-phosphatase-α (G6Pase-α) deficiency-induced carbohydrate metabolism disorder. Although hyperlipidemia is a hallmark of GSDI, the extent of lipid metabolism disruption remains incompletely understood. Lipidomic analysis was performed to characterize the serum lipidome in patients with GSDIa, by including age- and sex-matched healthy controls and age-matched hypercholesterolemic controls. Metabolic control and dietary information biochemical markers were obtained from patients with GSDIa. Patients with GSDIa showed higher total serum lysophosphatidylcholine (Fold Change, (FC) 2.2, P < 0.0001), acyl-acyl-phosphatidylcholine (FC 2.1, P < 0.0001), and ceramide (FC 2.4, P < 0.0001) levels and bile acid (FC 0.7, P < 0.001), acylcarnitines (FC 0.7, P < 0.001), and cholesterol esters (FC 1.0, P < 0.001) than those of healthy controls, and higher di- (FC 1.1, P < 0.0001; FC 0.9, P < 0.01) and triacylglycerol (FC 6.3, P < 0.0001; FC 3.9, P < 0.01) levels than those of healthy controls and hypercholesterolemic subjects. Both total cholesterol and triglyceride values correlated with Cer (d16:1/22:0), Cer (d18:1/20:0), Cer (d18:1/20:0(OH)), Cer (d18:1/22:0), Cer (d18:1/23:0), Cer (d18:1/24:1), Cer (d18:2/22:0), Cer (d18:2/24:1). Total cholesterol also correlated with Cer (d18:1/24:0), Cer (d18:2/20:0), HexCer (d16:1/22:0), HexCer (d18:1/18:0), and Hex2Cer (d18:1/20:0). Triglyceridelevels correlated with Cer (d18:0/24:1). Alanine aminotransferase values correlated with Cer (d18:0/22:0), insulin with Cer (d18:1/22:1) and Cer (d18:1/24:1), and HDL with hexosylceramide (HexCer) (d18:2/23:0). These results expand on the currently known involvement of lipid metabolism in GSDIa. Circulating Cer may allow for refined dietary assessment compared with traditional biomarkers. Because specific lipid species are relatively easy to assess, they represent potential novel biomarkers of GSDIa.

Metabolomic characterization of human glioblastomas and patient plasma: a pilot study

Background Glioblastoma (GBM) is a clinically challenging primary brain tumor with poor survival outcome despite surgical resection and intensive chemoradiation. The metabolic heterogeneity of GBM can become biomarkers for treatment response, resistance, and outcome prediction. The aim of the study is to investigate metabolic distinctions between primary and recurrent GBM tissue and patient plasma to establish feasibility for metabolic profiling. Methods A single-center cohort study analyzed tissue and blood samples from 15 patients with GBM using untargeted metabolomic/lipidomic assays. Metabolomic, lipidomic, and biogenic amine analyses were conducted on GBM tissue and patient plasma at diagnosis and recurrence using untargeted mass spectrometry. The study utilized a small but longitudinally collected cohort to evaluate alteration in metabolites, lipids, and biogenic amines between specimens at diagnosis and recurrence. Results Exploratory analysis revealed significant alteration in metabolites, lipids, and biogenic amines between diagnostic and recurrent states in both tumor and plasma specimens. Notable metabolites differed at recurrence, including N-alpha-methylhistamine, glycerol-3-phosphate, phosphocholine, and succinic acid in tissue, and indole-3-acetate, and urea in plasma. Principal component analysis revealed distinct metabolomic profiles between tumor tissue and patient plasma. Distinct metabolic profiles were observed in GBM tissue and patient plasma at recurrence, demonstrating the feasibility of using metabolomic methodologies for longitudinal studies. One patient exhibited a unique tumor resistance signature at diagnosis, possibly indicating a high-risk metabolomic phenotype. Conclusions In this small cohort, the findings suggest the potential of metabolomic signatures of GBM tissue and patient plasma for risk stratification, outcome prediction, and the development of novel adjuvant metabolic-targeting therapies. The findings suggest metabolic discrepancies at diagnosis and recurrence in tissue and plasma, highlighting potential implications for evaluation of clinical response. The identification of significant changes in metabolite abundance emphasizes the need for larger studies using targeted metabolomics to validate and further explore these profiles.

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

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

Novel eicosanoid signature in plasma provides diagnostic for metabolic dysfunction-associated steatotic liver disease

There is a clinical need for a simple test implementable at the primary point of care to identify individuals with metabolic dysfunction-associated steatotic liver disease (MASLD) in the population. Blood plasma samples from adult patients with varying phenotypes of MASLD were used to identify a minimal set of lipid analytes reflective of underlying histologically confirmed MASLD. Samples were obtained from the NIDDK Nonalcoholic Steatohepatitis Clinical Research Network (NASH CRN) NAFLD Database prospective cohort study (MASLD group; N = 301). Samples of control subjects were obtained from cohort studies at the University of California San Diego (control group; N = 48). Plasma samples were utilized for targeted quantitation of circulating eicosanoids, related bioactive metabolites, and polyunsaturated fatty acids by ultra-high performance liquid chromatography-mass spectrometry (UPLC-MS) lipidomics analysis. Bioinformatic approaches were used to discover a panel of bioactive lipids that can be used as a diagnostic tool to identify MASLD. The final panel of fifteen lipid metabolites consists of 12 eicosanoid metabolites and 3 free fatty acids that were identified to be predictive for MASLD by multivariate area under the receiver operating characteristics curve (AUROC) analysis. The panel was highly predictive for MASLD with an AUROC of 0.999 (95% CI = 0.986–1.0) with only one control misclassified. A validation study confirmed the resulting MASLD LIPIDOMICS SCORE, which may require a larger-scale prospective study to optimize. This predictive model should guide the development of a non-invasive “point-of-care” test to identify MASLD patients requiring further evaluation for the presence of metabolic dysfunction-associated steatohepatitis.

IPLA2β regulates the dual effects of arachidonic acid in thyroid cancer.

Abnormal arachidonic acid metabolism in the tumor microenvironment is closely related to cancer progression; however, thyroid cancer was rarely researched. Through lipidomic analysis, we disclosed that dysregulated arachidonic acid metabolism plays dual effects on thyroid cancer. The promoting role of arachidonic acid in the progression of thyroid cancer cells was evaluated utilizing cell viability (CCK-8 assay) and transwell invasion assays, confirmed by corresponding inhibitors. Lipid peroxidation and the use of various cell death inhibitors confirmed that arachidonic acid confers vulnerability to ferroptosis in thyroid cancer. The roles of arachidonic acid and ferroptosis inducer in thyroid cancer were assessed in a xenograft mouse model. On one hand, arachidonic acid promotes the progression of thyroid cancer through the cyclooxygenase/prostaglandin pathway; on another hand, arachidonic acid confers vulnerability to ferroptosis through lipoxygenases. Moreover, iPLA2β drives converse roles of arachidonic acid between cancer-progression and ferroptosis vulnerability through releasing free arachidonic acid from the cell membrane. Finally, we confirmed high arachidonic acid diet promotes the development of thyroid cancer in vivo, whereas ferroptosis inducer sulfasalazine dramatically reduced tumor growth of mice with feeding arachidonic acid. Our research demonstrated the roles of iPLA2β in conversing dual effects of arachidonic acid in thyroid cancer and provides ferroptosis inducer as a potential therapeutic strategy.

Shiitake mushroom-derived extracellular nanovesicles: Preparation, characterization, and inhibition of Caco-2 cells

In this study, Shiitake mushroom-derived extracellular nanovesicles (SMDENVs) were isolated from fresh Shiitake mushrooms by ultracentrifugation and sucrose gradient ultracentrifugation. The morphological characteristics of SMDENVs were investigated via Transmission Electron Microscopy and Laser Scanning Confocal Microscopy. SMDENVs were spherical, hollow, and uniform in size, with an average diameter of 177.6 ± 51.4 nm. Based on the analysis of lipidomics and proteomics, 383 lipids species and 1290 proteins were identified in SMDENVs. Compared with the conventional liposomes, SMDENVs demonstrated higher stability in different environmental conditions. Furthermore, we observed that SMDENVs were cytocompatible and inhibited the proliferation of Caco-2 cells. SMDENVs could be phagocytized by Caco-2 cells in a time-dependent manner. Further, SMDENVs also inhibited the proliferation of Caco-2 cells in a dose-dependent manner, and the half-maximal inhibitory concentration (IC50) was 236.2 ± 3.2 μg/mL. Additionally, SMDENVs induced cellular apoptosis by increasing the levels of reactive oxygen species and decreasing the mitochondrial membrane potential.

Effects of ultra-high pressure processing on microstructure, water distribution and lipidomics variances of Arabica coffee beans

The emerging non-thermal technique of ultra-high pressure (UHP) processing technology has seen significant advancements in food processing in recent years. The present study aimed to analyze the impact of UHP (100–300 MPa) processing on the color, microstructure, water distribution, and lipidomics variations of wet-processed Arabica coffee beans. The results indicated that the brightness and chromatic aberration of coffee beans were significantly altered by UHP processing, while other color parameters remained relatively unaffected. Scanning electron microscope examinations showed that UHP processing caused compression, compaction, and even collapse of the pore structure within coffee beans. Compared to wet-processed Arabica coffee beans, UHP processing promoted a more even water distribution and facilitated the conversion of bound and immobilized water into free water, with the maximum effect observed during UHP-200 treatment. Lipidomics analysis indicated that triacylglycerol (TAG, 24.75 %) and diacylglyceryl trimethylhomoserine (DGTS, 11.23 %). Notably, UHP-100, UHP-200, and UHP-300 samples exhibited 238, 191, and 788 differentially expressed lipids. The carbon chain length and degree of unsaturation of all differentially expressed lipids exhibited a pressure-dependent decrease with intricate interrelationships.

Abstract B036: Hypoxic cancer cells condition immunosuppressive macrophages via secreted non-protein mediators in pancreatic ductal adenocarcinoma

Abstract INTRODUCTION: Hypoxia is a defining feature of pancreatic ductal adenocarcinoma (PDAC) that contributes to the immunosuppressive microenvironment defined by increased tumor-associated macrophages (TAMs). However, there is an unmet need to define mechanisms by which hypoxia drives the immunosuppressive macrophage phenotype. We hypothesize that hypoxic cancer cells secrete non-protein metabolites to induce immunosuppressive phenotypes in macrophages. METHODS: We generated conditioned media (CM) by culturing the pancreatic adenocarcinoma cell line KPC under normoxia (21% O2) or hypoxia (0.5% O2) conditions for 48 hours. We treated bone marrow-derived macrophages (BMDMs) or the macrophage line RAW264.7 with CM. We assessed immunosuppressive gene expression using RNAseq and qRT-PCR. Proteins in CM were depleted using Sera-Mag Magnetic Carboxylate Modified Beads or denatured by boiling at 100°C for 15 minutes. We identified changes in metabolites between hypoxic and normoxic CM using HPLC. RESULTS: Compared to BMDMs treated with normoxic CM, we observed that BMDMs treated with hypoxic CM induced multiple immunosuppressive proteins (Arg1), cytokines (Ccl22, Cxcl3) and interleukins (Il1b, Il1a, Il6). Similarly, GSEA analysis demonstrated that hypoxic CM induced TNFa signaling via NfkB and IL6-JAK-STAT3 signaling. Consistent with RNA-seq analysis, qRT-PCR measured Arg1 expression 53 times higher in hypoxic CM-treated BMDMs compared to nomoxic CM (p=0.0286). Compared to normoxic CM, hypoxic CM stimulated macrophage migration, a marker for macrophage infiltration, as measured by transwell assays (p&amp;lt;0.0001). An increase in Arg1 expression in RAW264.7 cells was still observed when treated with protein depleted or boiled hypoxic CM, excluding proteins as soluble factor(s) mediating immunosuppression. To identify non-protein mediators of immune suppression, mass spectrometry quantified lipids and metabolites enriched in HCM. Metabolomic analysis identified 40 metabolites increased in hypoxic CM including the monounsaturated or polyunsaturated fatty acids linoelaidic acid, DGLA, and arachidonic acid. Similarly, lipidomic analysis revealed that multiple PC (phosphatidylcholine) and LPC (lysophosphatidylcholine) lipid species were enriched in HCM. CONCLUSION: We observe that hypoxic tumor cells induce immunosuppressive changes in macrophages likely via secreted non-protein metabolites. The hypoxic metabolome of PDAC tumor cells may be a key driver of the accumulation of immunosuppressive tumor associated macrophages. We are currently characterizing the role of individual lipids or metabolites in macrophage polarization. Citation Format: Matthew T Cribb, Sahar Fattani, Ayeisha Colon-Ortiz, Dadi Jiang, Michael Spiotto, Albert Koong. Hypoxic cancer cells condition immunosuppressive macrophages via secreted non-protein mediators in pancreatic ductal adenocarcinoma [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Advances in Pancreatic Cancer Research; 2024 Sep 15-18; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2024;84(17 Suppl_2):Abstract nr B036.

PSLBI-11 Relevance of mitochondrial-mediated apoptotic processes in color and oxidative stabilities of five different beef muscles

Abstract Fresh meat color stands as one of the most critical quality indicators influencing consumer perception of meat freshness and purchase decision. Variation in color and color stability among different muscle types exists due to differences in chemical compositions, including lipids and metabolites, and other redox stability-related biochemical properties. Understanding biochemical mechanisms governing color stability in different muscles will offer insights for the industry to develop practical strategies aimed at reducing food waste attributed to discoloration. The objective of the current study was to identify metabolites and lipid compounds potentially linked to oxidative stabilities and relevant biochemical properties across different bovine muscles. Five different muscles [longissimus lumborum (LL), gluteus medius (GM), biceps femoris (BF), semitendinosus (ST), and infraspinatus (IF)] were collected from 16 beef carcasses (USDA Choice) at 2-d postmortem. Multiple cuts were made from each muscle for meat color measurements including instrumental and sensory color evaluations during display, and biochemical attributes, including total reducing activity (TRA), mitochondria-swelling, mitochondrial-lipid oxidation, cytochrome c redox ability (CytC). For the lipidome and metabolome analyses, beef samples were extracted and profiled using non-targeted UPLC-MS analyses. Data analysis was conducted with Metaboanalyst 6.0. The correlation analysis was conduct with Pearson’s correlation and considered the significance level at P &amp;lt; 0.05. In brief, LL and ST maintained greater color stability, redox stability, and lipid/protein oxidative stabilities compared with BF and GM, with IF showing the least (P &amp;lt; 0.05). Also, IF had the greatest levels of mitochondrial-swelling, mitochondrial-lipid oxidation, and oxidized CytC compared with LL (P &amp;lt; 0.05). The ANOVA results found 1,410 significant features in the metabolome analysis and 531 in the lipidome analysis of beef samples. Utilizing partial least square-discriminant analysis (PLS-DA), scatter plots grouped the five muscle types into three distinct clusters: LL and ST, BF and GM, and IF. Pro-apoptotic factors such as phosphatidylserine and lysophosphatidylserine were greater in IF compared with LL and ST (P &amp;lt; 0.05). From the metabolome results, anti-apoptotic factors like creatine and glutathione were increased in LL and ST compared with IF, whereas pro-apoptotic spermidine and adenosine monophosphate (AMP) were greatest in IF (P &amp;lt; 0.05). CIE a* showed a positive correlation with phospholipids and mitochondria-swelling (P &amp;lt; 0.05). Chroma exhibited a positive correlation with TRA, creatine, cyclic AMP, and GMP (P &amp;lt; 0.05). The results suggest that variations in meat color stability among the five beef muscles were likely attributed to differences in the abundance of lipids and metabolites associated with redox and oxidative stabilities, as well as mitochondrial-mediated apoptotic pathways. Specifically, the varying abundance of pro-/anti-apoptotic factors across muscles indicates potential mechanistic biochemical linkages between the apoptosis and meat color. Further research is warranted to investigate the effects of extended aging periods on changes in apoptotic features and color stability of beef muscles.

An Untargeted Lipidomics Workflow Incorporating High-Resolution Demultiplexing (HRdm) Drift Tube Ion Mobility-Mass Spectrometry.

Global discovery lipidomics can provide comprehensive chemical information toward understanding the intricacies of metabolic lipid disorders such as dyslipidemia; however, the isomeric complexity of lipid species remains an analytical challenge. Orthogonal separation strategies, such as ion mobility (IM), can be inserted into liquid chromatography-mass spectrometry (LC-MS) untargeted lipidomic workflows for additional isomer separation and high-confidence annotation, and the emergence of high-resolution ion mobility (HRIM) strategies provides marked improvements to the resolving power (Rp > 200) that can differentiate small structural differences characteristic of isomers. One such HRIM strategy, high-resolution demultiplexing (HRdm), utilizes multiplexed drift tube ion mobility spectrometry (DTIMS) with post-acquisition algorithmic deconvolution to access high IM resolutions while retaining the measurement precision inherent to the drift tube technique; however, HRdm has yet to be utilized in untargeted studies. In this manuscript, a proof-of-concept study using ATP10D dysfunctional murine models was investigated to demonstrate the utility of HRdm-incorporated untargeted lipidomic analysis pipelines. Total lipid features were found to increase by 2.5-fold with HRdm compared to demultiplexed DTIMS as a consequence of more isomeric lipids being resolved. An example lipid, PC 36:5, was found to be significantly higher in dysfunctional ATP10D mice with two resolved peaks observed by HRdm that were absent in both the functional ATP10D mice and the standard demultiplexed DTIMS acquisition mode. The benefits of utilizing HRdm for discerning isomeric lipids in untargeted workflows have the potential to enhance our analytical understanding of lipids related to disease complexity and biologically relevant studies.

Integrated volatolomics and lipidomics analysis reveal the characteristic flavor formation mechanism in steamed large yellow croaker (Pseudosciaena crocea)

The internal relationship between lipid composition and characteristic flavor in the steamed large yellow croaker (LYC) was investigated using volatolomics, lipidomics, and electronic sensory systems. Compared to fresh LYC, the concentrations of five key volatile flavor compounds detected after steaming exceeded human sensory thresholds. Notably, nonanal, hexanal, and 1-octen-3-ol significantly influenced the flavor of the cooked meat. Steaming at 70 °C enhanced the LYC flavor profile, with the strongest flavor observed at 80 °C. The content of three key volatile flavor compounds peaked, especially hexanal, which reached 54.55 μg/kg. Phosphatidylcholines, triacylglycerols, and fatty acids were closely associated with the volatile flavor profile of steamed LYC. The oxidation of FA 22:6 was identified as a crucial source of flavor in LYC. This study aimed to improve consumer experience by exploring the nutritional quality and flavor formation mechanisms in the thermal processing of LYC.

Relationship between systemic biomarker of lipid peroxidation 4-hydroxynonenal and lipidomic profile of morbidly obese patients undergoing bariatric surgery

Obesity is characterized by fat accumulation, impaired metabolism and oxidative stress, frequently associated with lipid peroxidation and generation of bioactive 4-hydroxynonenal (4-HNE). This study aimed to evaluate the impact of bariatric surgery-induced weight loss on lipid peroxidation and associated perturbations in lipid profile. Plasma samples of twenty obese individuals before and 6 months after bariatric surgery were collected in addition to samples of ten healthy controls. HILIC-LC-MS/MS platform was used to characterize phospholipid profile, while lipid peroxidation markers 15-F2t-IsoP, 10-F4t-NeuroP and reactive aldehyde 4-HNE were quantified by RP-LC-MS/MS and GC-MS, respectively. Six months post-surgery lipid peroxidation markers decreased significantly and the BMI of morbidly obese patients decreased by 13 on average. Lipidomics analysis, identified 117 phospholipid species from seven classes, and showed obesity-associated lipidome perturbations, particularly in ether-linked phosphatidylethanolamines (PEo). A total of 45 lipid species were found to be significantly altered with obesity, while 10 lipid species correlated with lipid peroxidation markers. Sample pairwise analyses indicated an interesting link between 4-HNE and the amount of two PEos, PEo (38:2) and PEo (36:2). The results indicate that weight loss-induced improvement of redox homeostasis together with changes in lipid metabolites may serve as markers of metabolic improvement. However, further studies are needed to understand the role of obesity-induced oxidative stress on ether lipid biosynthesis and lipidome perturbations, as well as the impact of bariatric surgery on metabolic improvement.

Metabolomic, lipidomic and transcriptomic reveal meat quality differences among hybrid, indigenous and commercial broiler

With the improvement in living standards, breeders need to improve meat quality to meet consumers' demands. Hybrid (HB), indigenous (IB), and commercial broiler (CB) are the most essential components in consumer market. However, the difference in meat quality and underlying mechanism remains unclear. Our study found that HB showed significant differences in meat-quality performance compared with IB and CB, especially in breast muscle's shear force and meat color. Furthermore, metabolomic, lipidomic, and RNA-seq were performed to screen the critical molecular networks contributing to the performance difference. Most differentially expressed metabolites (DEMs) were significantly associated with shear force and a∗value and enriched in lipid metabolism-related pathways. The lipidomic analysis detected many differentially expressed lipids (DELs), especially between HB and CB. Most showed a positive association with a∗ and b∗ value and a negative association with shear force. RNA-seq analysis screened 275 and 497 differentially expressed genes (DEGs) in HB compared with IB and CB, and they were also highly associated with metabolism pathways and meat-quality performance. Finally, integrative analysis was conducted to screen the core DEMs, DELs and DEGs contributing to meat-quality performance. Our findings provided knowledge for molecular markers to facilitate the selection of chicken meat quality.

Distinct plasma lipids predict axonal injury and multiple sclerosis activity

BackgroundLipids are of particular interest for the study of neuroinjury and neuroinflammation as structural lipids are major components of myelin, and a variety of lipid species modulate inflammation. In this...

3,5-Dimethyl-2,4,6-trimethoxychalcone Lessens Obesity and MAFLD in Leptin-Deficient ob/ob Mice.

Chalcones constitute an important group of natural compounds abundant in fruits and comestible plants. They are a subject of increasing interest because of their biological activities, including anti-diabetic and anti-obesity effects. The simple chalcone structural scaffold can be modified at multiple sites with different chemical moieties. Here, we generated an artificial chalcone, i.e., 3,5-dimethyl-2,4,6-trimethoxychalcone (TriMetChalc), derived from 2',4'-Dihydroxy-6'-methoxy-3',5'-dimethylchalcone (DMC). DMC is a major compound of Cleistocalyx operculatus, a plant widely used in Asia for its anti-hyperglycemic activity. Using ob/ob mice as an obesity model, we report that, after 3 weeks of per os administration, TriMetChalc modified food intake through the specific activation of brain structures dedicated to the regulation of energy balance. TriMetChalc also decreased weight gain, glucose intolerance, and hepatic steatosis. Moreover, through extensive liver lipidomic analysis, we identified TriMetChalc-induced modifications that could contribute to improving the liver status of the animals. Hence, TriMetChalc is a chalcone derivative capable of reducing food intake and the addition of glucose intolerance and hepatic steatosis in a mouse model of obesity. In light of these results, we believe that TriMetChalc action deserves to be more deeply evaluated over longer treatment periods and/or in combination with other chalcones with protective effects on the liver.

Effect of flaxseed oil cyclolinopeptides on lipid oxidation, protein oxidation, and lipid profile during in vitro digestion of high-fat beef

This study investigated the influence of flaxseed oil cyclolinopeptides (CLs) on lipid and protein oxidation during high-fat meat digestion. Fourteen CLs were identified in flaxseed oil through UHPLC-ESI-QTOF-MS/MS, with dominant CLA, CLB, CLE, and CLM. During in vitro digestion, CLs inhibited lipid oxidation products (lipid hydroperoxide, Malondialdehyde, and 4-hydroxynonenal) and protein carbonylation. Compared to other groups, the lipid (16.28 ± 0.35) and protein (17.5 ± 0.6) oxidation was significantly inhibited, and antioxidant activity was remarkably increased when the CLs content reached 200 mg/kg. Through untargeted lipidomic analysis using Q-Exactive, it was observed that CLs mitigated the formation of oxidized triglycerides (OxTG) products and enhanced the hydrolysis of lipids to generate sphingolipid and polyunsaturated fatty-acids enriched glycerophospholipids imparting nutritional value to meat. Electron spin-resonance and fluorescence quenching showed that primary radicals such as alkyl and alkoxy radicals during high-fat meat digestion with flaxseed oil CLs significantly mitigate their formation. These findings collectively indicate that consuming CLs enriched flaxseed oil could reduce lipid oxidation and enhance the nutritional value of high-fat meat during digestion.

Comprehensive lipidomic profiling of human milk from lactating women across varying lactation stages and gestational ages

An untargeted lipidomic analysis was conducted to investigate the lipid composition of human milk across different lactation stages and gestational ages systematically. A total of 25 lipid subclasses and 934 lipid species as well as 90 free fatty acids were identified. Dynamic changes of the lipids throughout lactation and gestational phases were highlighted. In general, lactation stages introduced more variations in the lipid composition of human milk than gestational ages. Most lipids decreased as the milk progressed from the colostral stage to the mature stage, with some reaching a peak at the transitional stage. Significant variations in lipid composition across gestational ages were predominantly evident during early lactation period. In mature milks, most of the lipids exhibited no discernible statistical differences among gestational ages. This elucidation offers valuable insights and guidance for tailoring precise nutritional strategies for infants with diverse health needs.

Integrative metagenomic and lipidomic analyses reveal alterations in children with obesity and after lifestyle intervention.

Despite emerging evidence linking alterations in gut microbiota to childhood obesity, the metabolic mechanisms linking gut microbiota to the lipid profile during childhood obesity and weight loss remain poorly understood. In this study, children with obesity were treated with lifestyle weight loss therapy. Metagenomics association studies and serum untargeted lipidomics analyses were performed in children with obesity and healthy controls before and after weight loss. We identified alterations in gut microbiota associated with childhood obesity, as well as variations in circulating metabolite concentrations. Children with obesity showed significant decreases in the levels of s-Rothia_kristinae and s-Enterobacter_roggenkampii, alongsige elevated levels of s-Clostridiales_bacterium_Marseille-P5551. Following weight loss, the levels of s-Streptococcus_infantarius and s-Leuconostoc_citreum increased by factors of 3.354 and 1.505, respectively, in comparison to their pre-weight loss levels. Correlation analyses indicated a significant positive relationship between ChE(2:0) levels and both with s-Lachnospiraceae_bacterium_TF09-5 and fasting glucose levels. CoQ8 levels were significantly negatively correlated with s-Rothia_kristinae and HOMA-IR. We linked altered gut microbiota and serum lipid levels in children with obesity to clinical indicators, indicating a potential impact on glucose metabolism via lipids. This study contributes to understanding the mechanistic relationship between altered gut microbiota and childhood obesity and weight loss, suggesting gut microbiome as a promising target for intervention. https://www.chictr.org.cn/showproj.html?proj=178971, ChiCTR2300072179.