Mass spectrometric approaches in discovering lipid biomarkers for COVID-19 by lipidomics: Future challenges and perspectives.

Coronavirus disease 2019 (COVID-19) has emerged as a global health threat and has rapidly spread worldwide. Significant changes in the lipid profile before and after COVID-19 confirmed the significance of lipid metabolism in regulating the response to viral infection. Therefore, understanding the role of lipid metabolism may facilitate the development of new therapeutics for COVID-19. Owing to their high sensitivity and accuracy, mass spectrometry (MS)-based methods are widely used for rapidly identifying and quantifying of thousands of lipid species present in a small amount of sample. To enhance the capabilities of MS for the qualitative and quantitative analysis of lipids, different platforms have been combined to cover a wide range of lipidomes with high sensitivity, specificity, and accuracy. Currently, MS-based technologies are being established as efficient methods for discovering potential diagnostic biomarkers for COVID-19 and related diseases. As the lipidome of the host cell is drastically affected by the viral replication process, investigating lipid profile alterations in patients with COVID-19 and targeting lipid metabolism pathways are considered to be crucial steps in host-directed drug targeting to develop better therapeutic strategies. This review summarizes various MS-based strategies that have been developed for lipidomic analyzes and biomarker discoveries to combat COVID-19 by integrating various other potential approaches using different human samples. Furthermore, this review discusses the challenges in using MS technologies and future perspectives in terms of drug discovery and diagnosis of COVID-19.

A facile method for monitoring sphingomyelin synthase activity in HeLa cells using liquid chromatography/mass spectrometry.

Sphingomyelin synthase (SMS) is a sphingolipid-metabolizing enzyme involved in the de novo synthesis of sphingomyelin (SM) from ceramide (Cer). Recent studies have indicated that SMS is a key therapeutic target for metabolic diseases such as fatty liver, type 2 diabetes, atherosclerosis, and colorectal cancer. However, very few SMS inhibitors have been identified because of the limited sensitivity and selectivity of the current fluorescence-based screening assay. In this study, we developed a simple cell-based assay coupled with liquid chromatography/tandem mass spectrometry (LC-MS/MS) to screen for SMS inhibitors. HeLa cells stably expressing SMS1 or SMS2 were used for the screening. A non-fluorescent unnatural C6-Cer was used as a substrate for SMS to produce C6-SM. C6-Cer and C6-SM levels in the cells were monitored and quantified using LC-MS/MS. The activity of ginkgolic acid C15:1 (GA), a known SMS inhibitor, was measured. GA had half-maximal inhibitory concentrations of 5.5 µM and 3.6 µM for SMS1 and SMS2, respectively. To validate these findings, hSMS1 and hSMS2 proteins were optimized for molecular docking studies. In silico analyses were conducted to assess the interaction of GA with SMS1 and SMS2, and its binding affinity. This study offers an analytical approach for screening novel SMS inhibitors and provides in silico support for the experimental findings.

Determination of short-chain fatty acids by N,N-dimethylethylenediamine derivatization combined with liquid chromatography/mass spectrometry and their implication in influenza virus infection.

Short-chain fatty acids (SCFAs) are the end products of the fermentation of complex carbohydrates by the gut microbiota. Although SCFAs are recognized as important markers to elucidate the link between gut health and disease, it has been difficult to analyze SCFAs with mass spectrometry technologies due to their poor ionization efficiency and high volatility. Here, we present a novel and sensitive method for the quantification of SCFAs, including C2-C6 SCFAs and their hydroxy derivatives, by liquid chromatography/tandem mass spectrometry (LC-MS/MS) upon N,N-dimethylethylenediamine (DMED) derivatization with a run time of 10 min. Moreover, the quantification method of DMED-derivatized SCFAs in intestinal contents using isotope-labeled internal standards was also established. The method validation was performed by analyzing spiked intestinal samples; the limits of detection and quantification of SCFAs with this method were found to be 0.5 and 5 fmol, respectively; the recovery was greater than 80% and good linearity (0.9932 to 0.9979) of calibration curves was obtained over the range from 0.005 to 5000 pmol/µL; the intraday and interday precisions were achieved in the range of 1-5%. Furthermore, the validated method was applied to analyze SCFAs in the cecum and colon contents of mice infected with the influenza virus. The results showed that the concentration of most of the SCFAs tested here decreased significantly in a time-dependent manner after the infection, suggesting a possibility that SCFAs in intestinal samples could be used as severe disease markers. Overall, we here successfully developed a simple, fast, and sensitive method for SCFA analysis by LC-MS/MS combined with DMED derivatization. The method for the quantification of SCFAs will be a useful tool for both basic research and clinical studies.

Sphingosine-1-phosphate interactions in the spleen and heart reflect extent of cardiac repair in mice and failing human hearts.

Sphingosine-1-phosphate (S1P) is a bioactive mediator in inflammation. Dysregulated S1P is demonstrated as a cause of heart failure (HF). However, the time-dependent and integrative role of S1P interaction with receptors in HF is unclear after myocardial infarction (MI). In this study, the sphingolipid mediators were quantified in ischemic human hearts. We also measured the time kinetics of these mediators post-MI in murine spleen and heart as an integrative approach to understand the interaction of S1P and respective S1P receptors in the transition of acute (AHF) to chronic HF (CHF). Risk-free 8-12 wk male C57BL/6 mice were subjected to MI surgery, and MI was confirmed by echocardiography and histology. Mass spectrometry was used to quantify sphingolipids in plasma, infarcted heart, spleen of mice, and ischemic and healthy human heart. The physiological cardiac repair was observed in mice with a notable increase of S1P quantity (pmol/g) in the heart and spleen significantly reduced in patients with ischemic HF. The circulating murine S1P levels were increased during AHF and CHF despite lowered substrate in CHF. The S1PR1 receptor expression was observed to coincide with the respective S1P quantity in mice and human hearts. Furthermore, selective S1P1 agonist limited inflammatory markers CCL2 and TNF-α and accelerated reparative markers ARG-1 and YM-1 in macrophages in the presence of Kdo2-Lipid A (KLA; potent inflammatory stimulant). This report demonstrated the importance of S1P/S1PR1 signaling in physiological inflammation during cardiac repair in mice. Alteration in these axes may serve as the signs of pathological remodeling in patients with ischemia.NEW & NOTEWORTHY Previous studies indicate that sphingosine-1-phosphate (S1P) has some role in cardiovascular disease. This study adds quantitative and integrative systems-based approaches that are necessary for discovery and bedside translation. Here, we quantitated sphinganine, sphingosine, sphingosine-1-phosphate (S1P) in mice and human cardiac pathobiology. Interorgan S1P quantity and respective systems-based receptor activation suggest cardiac repair after myocardial infarction. Thus, S1P serves as a therapeutic target for cardiac protection in clinical translation.

Docosahexaenoic Acid Esters of Hydroxy Fatty Acid Is a Novel Activator of NRF2.

Fatty acid esters of hydroxy fatty acids (FAHFAs) are a new class of endogenous lipids with interesting physiological functions in mammals. Despite their structural diversity and links with nuclear factor erythroid 2-related factor 2 (NRF2) biosynthesis, FAHFAs are less explored as NRF2 activators. Herein, we examined for the first time the synthetic docosahexaenoic acid esters of 12-hydroxy stearic acid (12-DHAHSA) or oleic acid (12-DHAHOA) against NRF2 activation in cultured human hepatoma-derived cells (C3A). The effect of DHA-derived FAHFAs on lipid metabolism was explored by the nontargeted lipidomic analysis using liquid chromatography-mass spectrometry. Furthermore, their action on lipid droplet (LD) oxidation was investigated by the fluorescence imaging technique. The DHA-derived FAHFAs showed less cytotoxicity compared to their native fatty acids and activated the NRF2 in a dose-dependent pattern. Treatment of 12-DHAHOA with C3A cells upregulated the cellular triacylglycerol levels by 17-fold compared to the untreated group. Fluorescence imaging analysis also revealed the suppression of the degree of LDs oxidation upon treatment with 12-DHAHSA. Overall, these results suggest that DHA-derived FAHFAs as novel and potent activators of NRF2 with plausible antioxidant function.

Identification of short-chain fatty acid esters of hydroxy fatty acids (SFAHFAs) in a murine model by nontargeted analysis using ultra-high-performance liquid chromatography/linear ion trap quadrupole-Orbitrap mass spectrometry.

RATIONALE: Fatty acid esters of hydroxy fatty acids (FAHFAs) are recently discovered endogenous lipids with outstanding health benefits. FAHFAs are known to exhibit antioxidant, antidiabetic and anti-inflammatory properties. The number of known long-chain FAHFAs in mammalian tissues and dietary resources increased recently because of the latest developments in high-resolution tandem mass spectrometry techniques. However, there are no reports on the identification of short-chain fatty acid esterified hydroxy fatty acids (SFAHFAs). METHODS: Intestinal contents, tissues, and plasma of rats fed with high-fat diet (HFD) and normal diet (ND) were analyzed for fatty acids, hydroxy fatty acids, and FAHFAs using ultra-high-performance liquid chromatography (UHPLC) and linear trap quadrupole-Orbitrap mass spectrometry (LTQ Orbitrap MS) with negative heated electrospray ionization. RESULTS: Untargeted analysis of total lipid extracts from murine samples (male 13-week-old WKAH/HKmSlc rats) led to the identification of several new SFAHFAs of acetic acid or propanoic acid esterified long-chain (>C20)-hydroxy fatty acids. Furthermore, MS3 analysis revealed the position of the hydroxyl group in the long-chain fatty acid as C-2. The relative amounts of SFAHFAs were quantified in intestinal contents and their tissues (Cecum, small intestine, and large intestine), liver, and plasma of rats fed with HFD and ND. The large intestine showed the highest abundance of SFAHFAs with a concentration range from 0.84 to 57 pmol/mg followed by the cecum with a range of 0.66 to 28.6 pmol/mg. The SFAHFAs were significantly altered between the HFD and ND groups, with a strong decreasing tendency under HFD conditions. CONCLUSIONS: Identification of these novel SFAHFAs can contribute to a better understanding of the chemical and biological properties of individual SFAHFAs and their possible sources in the gut, which in turn helps us tackle the role of these lipids in various metabolic diseases.

Identification of hydroxy- and keto-dicarboxylic acids in remote marine aerosols using gas chromatography/quadruple and time-of-flight mass spectrometry.

RATIONALE: The identification of hydroxy- and keto-dicarboxylic acids (diacids) in remote marine aerosol samples is important for a better understanding of the composition of organic particulate matter, as this chemical composition is essential for predicting the effects on climate, air quality, and human health. Molecular characterization of these compounds provides insights into sources and formation pathways of organic aerosols. METHODS: The method of chemical derivatization followed by gas chromatography-flame ionization detection (GC-FID), gas chromatography/quadruple mass spectrometry (GC/QMS) and gas chromatography/time-of-flight mass spectrometry (GC/TOFMS) was used to identify hydroxy- and keto-diacids in remote marine aerosols. Atmospheric samples were collected at Chichijima Island in the western North Pacific and the diacids and related compounds were extracted with organic-free ultrapure water. A two-step derivatization technique was employed, using 14% BF3 /n-butanol for the butylation of carboxyl groups and acidic ketones followed by N,O-bis(trimethylsilyl)trifluoroacetamide (BSTFA) for the trimethylsilylation of hydroxyl groups. RESULTS: Several new peaks were detected in the gas chromatogram after trimethylsilylation of the dibutyl ester fraction. Based on mass spectral interpretation with authentic standards, we successfully identified and quantified a homologous series of hydroxydiacids, including tartaric and oxaloacetic acids. In addition, transformation of oxaloacetic acid into its enol form was elucidated. CONCLUSIONS: Utilizing GC-FID, GC/QMS and GC/TOFMS, hydroxy- and keto-diacids were identified in the remote marine aerosols. A complete structural characterization was achieved with extensive mass spectral analysis. Molecular distributions of hydroxydiacids generally showed the predominance of malic acid followed by tartronic acid. We consider that these hydroxydiacids are important intermediates in the atmospheric oxidation of organic aerosols to result in smaller diacids. Copyright © 2016 John Wiley & Sons, Ltd.

Exploration of New Lipid Nutrients and Their Characterization in Herbal Teas Using Non-Targeted Liquid Chromatography-Mass Spectrometry.

Herbal teas are blends of leaves, seeds, fruits, and flowers from various plants that provide relaxation, anti-inflammatory benefits, and immune system support for conditions such as diabetes and asthma. Despite their health benefits, comprehensive lipidomic data on herbal teas are limited in the literature. We used non-targeted liquid chromatography-linear ion trap orbitrap mass spectrometry to identify and correlate the lipid species in the following six herbal tea samples: fennel, ginger, juniper, lemon peel, orange peel, and rosehip. A total of 204 lipid molecular species were identified, and multivariate analysis revealed a significant difference between lipid species in herbal teas. Saturated fatty acids (SFAs) and polyunsaturated fatty acids (PUFAs) are significantly abundant in juniper, including ω-3 and ω-6 fatty acids, followed by fennel. Cluster correlations showed that ginger contained mainly sphingolipids and lysophospholipids, whereas fennel was rich in phospholipids. No significant variations in the content of triacylglycerols were observed in any of the herbal teas analyzed. The ratio of PUFAs to SFAs in herbal teas showed that orange peel had the highest ratio, followed by lemon peel and fennel, indicating their potential health benefits. In addition, using high-resolution mass spectrometry, various lipids such as fatty acid esters of hydroxy fatty acids and N-acyl-lysophosphatidylethanolamines were identified and characterized in these herbal teas. This study provides a comprehensive lipid analysis and detailed characterization of lipids in six herbal teas, highlighting their plausible applications in the field of nutrition and various food industries for the development of functional foods.

Dissecting new lipids and their composition in herbal tea using untargeted LC/MS.

Herbal teas and beverages have gained global attention because they are rich in natural bioactive compounds, which are known to have diverse biological effects, including antioxidant and anticarcinogenic properties. However, the lipidomic profiles of herbal teas remain unclear. In this study, we applied an untargeted lipidomics approach using high-performance liquid chromatography coupled with linear ion trap-Orbitrap mass spectrometry to comprehensively profile, compare, and identify unknown lipids in four herbal teas: dokudami, kumazasa, sugina, and yomogi. A total of 341 molecular species from five major classes of lipids were identified. Multivariate principal component analysis revealed distinct lipid compositions for each of the herbs. The fatty acid α-linolenic acid (FA 18:3) was found to be abundant in kumazasa, whereas arachidonic acid (FA 20:4) was the most abundant in sugina. Interestingly, novel lipids were discovered for the first time in plants; specifically, short-chain fatty acid esters of hydroxy fatty acids (SFAHFAs) with 4-hydroxy phenyl nonanoic acid as the structural core. This study provides insight into the lipidomic diversity and potential bioactive lipid components of herbal teas, offering a foundation for further research into their health-promoting properties and biological significance.

Regio-specific lipid fingerprinting of edible sea cucumbers using LC/MS.

Sea cucumbers are a rich source of bioactive compounds and are gaining popularity as nutrient-rich seafood. They are consumed as a whole organism in Pacific regions. However, limited data are available on the comparison of their lipid composition and nutritional value. In this study, untargeted liquid chromatography/mass spectrometry was applied to comprehensively profile lipids in the skin, meat, and intestinal contents of three color-distinct edible sea cucumbers. Multivariate principal component analysis revealed that the lipid composition of the intestinal contents of red, black, and blue sea cucumbers differs from that of skin, and meats. Polyunsaturated fatty acids (PUFAs) are abundant in the intestinal contents, followed by meats of sea cucumber. Lipid nutritional quality assessments based on fatty acid composition revealed a high P:S ratio, low index of atherogenicity, and high health promotion indices for the intestinal contents of red sea cucumber, suggesting its potential health benefits. In addition, hierarchical cluster analysis revealed that the intestinal contents of sea cucumbers were relatively high in PUFA-enriched phospholipids and lysophospholipids. Ceramides are abundant in black skin, blue meat, and red intestinal content samples. Overall, this study provides the first insights into a comprehensive regio-specific profile of the lipid content of sea cucumbers and their potential use as a source of lipid nutrients in food and nutraceuticals.

Sex-Specific Effect of Ethanol on Colon Content Lipidome in a Mice Model Using Nontargeted LC/MS.

Consumption of alcohol has widespread effects on the human body. The organs that are most significantly impacted are the liver and digestive system. When alcohol is consumed, it is absorbed in the intestines and processed by the liver. However, excessive alcohol use may affect gut epithelial integrity, microbiome composition, and lipid metabolism. Despite past studies investigating the effect of ethanol on hepatic lipid metabolism, the focus on colonic lipid metabolism has not been well explored. In this study, we investigated the sex-specific effect of ethanol on the colonic content lipidome in a mouse model using nontargeted liquid chromatography-mass spectrometry. Comprehensive lipidome analysis of colonic flush samples was performed using ethanol-fed (EF) and pair-fed (PF) mice of each sex. Partial least-squares discriminant analysis revealed that ethanol altered colonic lipid composition largely in male mice compared with female mice. A significant increase in free fatty acids, ceramides, and hexosylceramides and decreased phosphatidylglycerols (PG) was observed in the EF group compared to the PF group in male mice. Phosphatidylethanolamine (PE) levels were increased significantly in the EF group of both sexes compared to the PF group. The volcanic plot shows that PG (O-15:1/15:0) and PE (O-18:2/15:0) are common markers that are increased in both sexes of the EF group. In addition, decreased fatty acid esters of hydroxy fatty acids (FAHFA) were observed specifically in the EF group of female mice. Overall, a significant variation in the mice colonic content lipidome between the EF and PF groups was observed. Target pathways, such as sphingolipid metabolism in males, FAHFA in females, and PE metabolism in both sexes, were suggested. This study provides new insight into the sex-dependent lipid change associated with alcohol-induced gut-microbiota dysfunction and its potential health impacts.

Alterations in plasma short-chain fatty acids in preadolescence children: The Hokkaido study.

The purpose of this study is to explore the plasma short-chain fatty acid (SCFA) concentrations in 9-12-year-old Japanese children collected in the Hokkaido study, focusing on how factors such as age, sex, and body mass index (BMI) correlate with these levels. The Hokkaido Study on Children's Health is an ongoing longitudinal study since 2002, encompassing 20,926 pregnant women in Hokkaido Prefecture, Japan, between 2003 and 2012. We contacted 1881 children aged 9-12 born between April 2006 and January 2010, and 342 non-fasting plasma samples (boys = 181, girls = 161) were obtained from this cohort, alongside assessments of their height and weight. Plasma SCFA concentrations were determined using N,N-dimethylethylenediamine derivatization method coupled with liquid chromatography-mass spectrometry. Ethyl acetate was used to extract SCFAs from plasma, and the recovery ranged from 83 % to 108 %. Our findings indicate that acetic acid had the highest concentration across all age groups and sexes. The concentrations of butyric acid, valeric acid, and hexanoic acid increased with age, peaking in 12-year-old children. Conversely, the level of 4-hydroxy valeric acid showed a decreasing trend with increasing age groups. This study also explored the correlation between BMI and SCFA concentrations, comparatively higher level of propionic acid was observed in the overweight group. The results obtained in this study enhance our understanding of the role of SCFAs in the growth and development of children and provide a foundation for future nutritional intervention and health promotion strategies.

Quantitative determination of plasma cholesteryl ester levels in Japanese preadolescents from the Hokkaido study using liquid chromatography/tandem mass spectrometry.

Cholesteryl esters (CE) are sterols comprising various fatty acyl chains attached to a cholesterol hydroxyl moiety. CEs are often considered plasma biomarkers of liver function; however, their absolute concentrations in the plasma of Japanese preadolescents have not been well explored. This study aimed to determine the plasma CE levels in Japanese preadolescents of different sexes, ages, and body weights living in Hokkaido, Japan using targeted liquid chromatography/tandem mass spectrometry. The analysis was performed on the non-fasting plasma of preadolescents aged 9-12 years (n = 339 healthy volunteers; 178 boys and 161 girls) from Sapporo, Hokkaido, Japan. The analysis results showed that the total CE levels in boys and girls were 871 ± 153 and 862 ± 96 pmol/µL, respectively. CE 18:2 (41 ± 2.9 %) was found to be the most abundant species followed by CE 18:1 (16 ± 1.5 %) and CE 16:0 (13 ± 1.1 %). The ω-3 fatty acid-containing CEs such as CE 18:3 and CE 20:5 were significantly lower in girls than in boys. Despite the different ages, CEs were tightly regulated in the plasma of children's, and the total CEs ranged between 844 and 906 pmol/µL in boys and 824 and 875 pmol/µL in girls. The participants were further classified into three groups based on their body mass index underweight (n = 237), normal weight (n = 94), and overweight (n = 8). Most of the quantified CEs were accumulated in the overweight group. Interestingly, CE 18:3 was significantly upregulated in the overweight group compared to that in the normal range, and the area under the receiver operating characteristic curve was 0.73, suggesting that it could be a possible marker for obesity. This study marks the initial investigation of absolute CE levels in the plasma of children and can help elucidate the relationship between CEs and childhood obesity.

Synthesis and quantification of short-chain fatty acid esters of hydroxy fatty acids in rat intestinal contents and fecal samples by LC-MS/MS.

Short-chain fatty acid esters of hydroxy fatty acids (SFAHFAs) are a new class of endogenous lipids belonging to the fatty acid esters of the hydroxy fatty acid family. We previously uncovered their chemical structure and discussed their potential biological significance. We anticipate an increased need for SFAHFA measurements as markers of metabolic and inflammatory health. In this study, we synthesized sixty isomeric SFAHFAs by combining 12 hydroxy fatty acids (C16-C24) and five short-chain fatty acids (C2-C6) including a labelled internal standard. SFAHFA enrichment was achieved by solid-phase extraction and established a sensitive method for their quantitation by targeted LC-MS/MS. The method was applied to profile SFAHFAs in intestinal contents and fecal samples collected from rats fed a high-fat diet (HFD). The results demonstrated a significant decrease in SFAHFAs in the intestinal contents of the HFD group compared with the control group. The fecal time course (0-8 weeks) profile of SFAHFAs showed significant downregulation of acetic and propanoic acid esters in just 2 weeks after HFD administration. This study offers the first synthesis and quantitation method for SFAHFAs, demonstrating their potential use in elucidating SFAHFA sources, their role in various diseases, and potential biochemical signalling pathways.

Lipidomic study of kidney in a mouse model with urine flow obstruction.

Obstructed urine flow is known to cause structural and functional kidney damage leading to renal fibrosis. However, limited information is available on the change in kidney lipids during urinary tract obstruction. In this study, we investigated the change in lipidome in a mouse model with unilateral ureteral obstruction (UUO). The establishment of the UUO model was confirmed by histopathological examination using transmission electron microscopy. Untargeted liquid chromatography/mass spectrometry was carried out over a time course of 4 and 7 days. Compared to the sham control, the UUO kidney at 7 days showed dilatation of the renal tubule with loss of brush borders and thickening of the capillary endothelium. In the kidney lipidomes obtained from the UUO 7 days group compared to the control, a significant decrease of ceramide, sphingomyelin, phosphatidylcholine, lysophospholipids, and phosphatidylethanolamine was observed, whereas cholesteryl esters, free fatty acids, phosphatidylglycerol, and cardiolipins were significantly increased. The present study revealed the disturbed lipid metabolism in the UUO model, which may provide a clue to potential lipid pathways and therapeutic targets for the early stage of renal fibrosis.

Determination of plasma lysophosphatidylethanolamines (lyso-PE) by LC-MS/MS revealed a possible relation between obesity and lyso-PE in Japanese preadolescent children: the Hokkaido study.

BACKGROUND: Lysophosphatidylethanolamines (lyso-PEs) are the partial hydrolysis products of phosphatidylethanolamine. Although lyso-PEs are important biomarkers in various diseases, their determination is limited by the lack of simple and efficient quantification methods. This study aims to develop an improved quantitative method for the determination of lyso-PEs and its application to an epidemiological study. METHODS: Single reaction monitoring channels by collision-induced dissociation for seven lyso-PEs were established using liquid chromatography-tandem mass spectrometry. Plasma lyso-PEs were extracted with a single-phase method using an isotopically labeled internal standard for quantification. The proposed method was adopted to define lyso-PEs in plasma samples of children aged 9-12 years living in Sapporo, Japan. RESULTS: The limit of detection and limit of quantification for each lyso-PE ranged between 0.001-0.015 and 0.002-0.031 pmol/µL, respectively. Recoveries were found to be > 91% for all the species. The analysis results of children's plasma showed that the total lyso-PE concentrations in boys (n = 181) and girls (n = 161) were 11.53 and 11.00 pmol/µL (median), respectively. Participants were further classified by the percentage of overweight and subgrouped as underweight (n = 12), normal range (n = 292), or overweight (n = 38). Interestingly, the reduction of lyso-PE 16:0 and increased lyso-PE 22:6 were observed in overweight children compared with normal range (Fold change: 0.909 and 1.174, respectively). CONCLUSIONS: This study successfully established a simple quantitative method to determine lyso-PE concentrations. Furthermore, our method revealed the possible relation between plasma lyso-PEs and overweight status.

Sulfate-associated liquid water amplifies the formation of oxalic acid at a semi-arid tropical location over peninsular India during winter.

Aerosol liquid water (ALW) can serve as an aqueous-phase medium for numerous chemical reactions and consequently enhance the formation of secondary aerosols in a highly humid atmosphere. However, the aqueous-phase formation of secondary organic aerosols (SOAs) is not well understood in the Indian regions, particularly in tropical peninsular India. In this study, we collected total suspended particulate samples (n = 30) at a semiarid station (Ballari; 15.15°N, 76.93°E; 495 m asl) in tropical peninsular India during the winter of 2016. Homologous series of dicarboxylic acids (C2-C12), oxoacids (ωC2-ωC9), pyruvic acid (Pyr), and glyoxal (Gly) were determined by employing a water-extraction of aerosol and analyzed using capillary gas chromatography (GC). Results show that oxalic acid (C2) was the most abundant organic acid, followed by succinic (C4), malonic (C3), azelaic (C9), and glyoxylic (ωC2) or phthalic (Ph) acids. Total diacids-C accounted for 1.7-5.8 % of water-soluble organic carbon (WSOC) and 0.6-3.6 % of total carbon (TC). ALW, estimated from the ISORROPIA 2.1 model, showed a strong linear relationship with sulfate (SO42-), C2, C3, C4, ωC2, Pyr, and Gly. Based on molecular distribution, specific mass ratios (C2/C3, C2/C4, C2/Gly, and Ph/C9), linear relationships among the measured organic acids, ALW, organic (levoglucosan and oleic acid), and inorganic (SO42-) marker compounds, we emphasize that diacids and related organic compounds, especially C2, majorly form via aqueous-phase oxidation of precursor compounds including aromatic hydrocarbons (HCs) and unsaturated fatty acids (FAs) originated from biomass burning and combustion-related sources. The present study demonstrates that sulfate driven ALW largely enhances the formation of SOAs via the aqueous-phase reactions over tropical peninsular India during winter.

Lipid Composition Analysis and Characterization of Acyl Sterol Glycosides in Adzuki and Soybean Cultivars by Non-Targeted LC-MS.

Beans, a globally significant economic and nutritional food crop, are rich in polyphenolic chemicals with potential health advantages, providing high protein, fiber, minerals, and vitamins. However, studies on the global profiling of lipids in beans are limited. We applied a non-targeted lipidomic approach based on high-performance liquid chromatography coupled with linear ion trap-Orbitrap mass spectrometry (HPLC/LTQ-Orbitrap-MS) to comprehensively profile and compare the lipids in six distinct bean cultivars, namely, adzuki red beans-adzuki cultivar (ARB-AC), adzuki red beans-Benidainagon cultivar (ARB-BC), adzuki red beans-Erimoshouzu cultivar (ARB-EC), soybean-Fukuyutaka cultivar 2021 (SB-FC21), soybean-Fukuyutaka cultivar 2022 (SB-FC22), and soybean-Oosuzu cultivar (SB-OC). MS/MS analysis defined 144 molecular species from four main lipid groups. Multivariate principal component analysis indicated unique lipid compositions in the cultivars except for ARB-BC and ARB-EC. Evaluation of the concentrations of polyunsaturated fatty acid to saturated fatty acid ratio among all the cultivars showed that SB-FC21 and SB-FC22 had the highest value, suggesting they are the most beneficial for health. Furthermore, lipids such as acyl sterol glycosides were detected and characterized for the first time in these bean cultivars. Hierarchical cluster correlations revealed the predominance of ceramides in ARB-EC, lysophospholipids in SB-FC21, and glycerophospholipids in SB-OC. This study comprehensively investigated lipids and their compositions in beans, indicating their potential utility in the nutritional evaluation of beans as functional foods.

Regiospecific analysis of lipidome in the brain from mammals of land and aquatic habitats-by liquid chromatography-mass spectrometry.

The brain is a complex organ demonstrated by the occurrence of specific types of functional lipids. Despite some studies focusing on providing the animal brain lipid signature, there are limited studies focusing on the comprehensive and regiospecific characterization of multiple animal brain lipidome. Herein we characterized about 294 lipid molecular species from six different lipid classes in different portions of the brain after fixation from mammals of different habitats, fully-aquatic (n = 6), semi-aquatic (n = 6), and terrestrial (n = 4), using liquid chromatography-mass spectrometry. The untargeted brain lipid profiling revealed a significant difference in total lipid levels between fully-aquatic, semi-aquatic, and terrestrial mammals. The polyunsaturated fatty acids and cholesterol esters are abundant in brain tissue of semi-aquatic followed by fully-aquatic mammals whereas phosphatidylethanolamines are profoundly high in terrestrial species. The regiospecific analysis revealed a predominance of sphingolipids in all the groups but no significant differences were observed between the different portions of the brain such as the cerebellum, cortex, pons, spinal cord, and thalamus. Interestingly the multivariate analysis showed almost the same lipid compositions in the spinal cord and thalamus of terrestrial mammals. Overall, this is the first report to compare the comprehensive brain-lipidome among different mammalian groups inhabiting three distinct habitats. These results indicate that the brain lipid composition is specific to the animal habitat.

Detection and characterization of lipids in eleven species of fish by non-targeted liquid chromatography/mass spectrometry.

Fish is an important nutrition source because its lipids, which are rich in ω-3 fatty acids, are beneficial for human health. However, studies focusing on their detection, composition, and nutritional value are limited. In this study, we applied a non-targeted lipidomic approach based on ultra-high performance liquid chromatography coupled with linear-ion trap-Orbitrap mass spectrometry (UHPLC/LTQ-Orbitrap-MS) to comprehensively profile, compare, and detect unknown lipids in eleven types of dietary fish. A total of 287 molecular species from five major lipid classes were characterized by MS/MS analysis. Multivariate principal component analysis revealed the distinct lipid composition in shishamo smelt and Japanese sardine compared to other fish types. The assessment of nutritional indices based on the levels of free fatty acid suggested that among the eleven fish types, shishamo smelt is highly beneficial for health. Further, lipids such as N-acyl lysophosphatidylethanolamine were detected and characterized for the first time in fish fillets. Hierarchical cluster correlations indicated the predominance of glycerophospholipids (GPs) and sphingolipids in sardine, whereas fatty acyls and triacylglycerols (TAGs) were predominant in shishamo smelt. The high levels of polyunsaturated fatty acid-enriched GPs and TAGs in dietary fish endow it with great potential as a health-promoting food for human consumption. This study offers a comprehensive analysis of lipids and their compositions in fish fillets, demonstrating their potential use in the nutritional assessment of functional foods.