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.

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.

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.

First malaria in pregnancy followed in Philippine real-world setting: proof-of-concept of probabilistic record linkage between disease surveillance and hospital administrative data.

BACKGROUND: Although the Philippines targets malaria elimination by 2030, it remains to be a disease that causes considerable morbidity in provinces that report malaria. Pregnant women residing in endemic areas are a vulnerable population, because in addition to the risk of developing severe malaria, their pregnancy is not followed through, and the outcome of their pregnancy is unknown. This study determined the utility of real-world data integrated with disease surveillance data set as real-world evidence of pregnancy and delivery outcomes in areas endemic for malaria in the Philippines. METHODS: For the period of 2015 to 2019, electronic data sets of malaria surveillance data and Ospital ng Palawan hospital admission log of pregnant women residing in the four selected barangays of Rizal, Palawan were merged using probabilistic linkage. The source data for record linkage were first and last names, birth date, and address as the mutual variable. The data used for characteristics of the pregnant women from the hospital data set were admission date, discharge date, admitting and final diagnosis and body weight on admission. From the malaria surveillance data these were date of consultation, and malaria parasite species. The Levenshtein distance formula was used for a fuzzy string-matching algorithm. Chi-square test, and Mann-Whitney U test were used to compare the means of the two data sets. RESULTS: The prevalence of pregnant women admitted to the tertiary referral hospital, Ospital ng Palawan, was estimated to be 8.34/100 overall, and 11.64/100 from the four study barangays; that of malaria during pregnancy patients was 3.45/100 and 2.64/100, respectively. There was only one true-positive matched case from 238 women from the hospital and 54 women from the surveillance data sets. The overall Levenshstein score was 97.7; for non-matched cases, the mean overall score was 36.6 (35.6-37.7). The matched case was a minor who was hospitalized for severe malaria. The outcome of her pregnancy was detected from neither data set but from village-based records. CONCLUSIONS: This proof-of-concept study demonstrated that probabilistic record linkage could match real-world data in the Philippines with further validation required. The study underscored the need for more integrated and comprehensive database to monitor disease intervention impact on pregnancy and its outcome in the Philippines.

Kaempferol Improves Cardiolipin and ATP in Hepatic Cells: A Cellular Model Perspective in the Context of Metabolic Dysfunction-Associated Steatotic Liver Disease.

Targeting mitochondrial function is a promising approach to prevent metabolic dysfunction-associated steatotic liver disease (MASLD). Cardiolipin (CL) is a unique lipid comprising four fatty acyl chains localized in the mitochondrial inner membrane. CL is a crucial phospholipid in mitochondrial function, and MASLD exhibits CL-related anomalies. Kaempferol (KMP), a natural flavonoid, has hepatoprotective and mitochondrial function-improving effects; however, its influence on CL metabolism in fatty liver conditions is unknown. In this study, we investigated the effects of KMP on mitochondrial function, focusing on CL metabolism in a fatty liver cell model (linoleic-acid-loaded C3A cell). KMP promoted mitochondrial respiratory functions such as ATP production, basal respiration, and proton leak. KMP also increased the gene expression levels of CPT1A and PPARGC1A, which are involved in mitochondrial ß-oxidation. Comprehensive quantification of CL species and related molecules via liquid chromatography/mass spectrometry showed that KMP increased not only total CL content but also CL72:8, which strongly favors ATP production. Furthermore, KMP improved the monolysocardiolipin (MLCL)/CL ratio, an indicator of mitochondrial function. Our results suggest that KMP promotes energy production in a fatty liver cell model, associated with improvement in mitochondrial CL profile, and can serve as a potential nutrition factor in preventing MASLD.

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.

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.

Identification of a ß-Carboline Alkaloid from Chemoselectively Derived Vanilla Bean Extract and Its Prevention of Lipid Droplet Accumulation in Human Hepatocytes (HepG2).

Targeting bioactive compounds to prevent lipid droplet accumulation in the liver, we explored an antioxidative extract from vanilla bean (Vainilla planifolia) after chemo-selective derivatization through heating and acid modification. The chemical analysis of vanilla bean extract through chemoselective derivatization resulted in the identification of sixteen compounds (34-50) using LC-MS/MS analysis. A ß-carboline alkaloid with a piperidine C-ring and a vanillin moiety at C-1 (34) was identified by molecular networking and diagnostic fragmentation filtering approaches. ß-carboline alkaloid 34 exhibited significant inhibitory activity of lipid droplet accumulation (LDAI) in oleic acid-loaded hepatocellular carcinoma HepG2 cells. The LDAI activity was associated with both activation of lipolysis and suppression of lipogenesis in the cells. The study indicates that crude plant extracts, following chemoselective derivatization, may contain bioactive compounds that could be beneficial in preventing hepatosteatosis and could serve as a source of lead compounds for drug development. This approach may be useful to investigate other mixtures of natural products and food resources.

Sample pretreatment effects on isotopic compositions of oxygen and sulfur in BaSO4 derived from atmospheric sulfate.

RATIONALE: Preparation of BaSO4 from samples of atmospheric rain, snow, and aerosols has been used for δ18 O and δ34 S analyses. In the present study, we investigated the effect of various sample pretreatments on δ18 O and δ34 S values determined from a Na2 SO4 reagent solution and samples of atmospheric precipitation to improve assay time and cost efficiency. METHODS: BaSO4 was prepared from a Na2 SO4 solution by (a) evaporative concentration, (b) evaporation to dryness, (c) evaporation to dryness after adding HCl, and (d) evaporation to concentration after adding HCl, followed by cooling and then precipitation using a BaCl2 solution. To analyze the atmospheric precipitation samples for δ18 O, BaSO4 prepared from the samples was treated with diethylenetriaminepentaacetic acid (DTPA) and SO4 2- and separated chromatographically. The values of δ18 O and δ34 S were measured using a continuous-flow elemental analyzer coupled to an isotope-ratio mass spectrometer. RESULTS: The δ34 S values in BaSO4 precipitated from Na2 SO4 solution determined by methods (a)-(c) were consistent within precisions of ±0.5‰. The δ18 O values of methods (a) and (b) were consistent within ±0.2‰, whereas the δ18 O values of methods (c) and (d) increased with increasing HCl concentrations. Similar results were obtained from samples of atmospheric precipitations. The δ18 O values from DTPA-treated BaSO4 were consistent with those obtained by chromatographic separation within ±0.5‰. CONCLUSIONS: We found no significant differences in the effects of various pretreatments (acidification, heating, concentration, and drying) on δ18 O and δ34 S values in sulfate from samples of atmospheric precipitation and aerosols extracted as BaSO4 if HCl was not added to the sample before heating and BaSO4 was treated with DTPA for the δ18 O analysis.

Plasmalogen Profiling in Porcine Brain Tissues by LC-MS/MS.

Plasmalogen, a functional glycerophospholipid, is known for its beneficial nutritional effects, such as anti-oxidation and anti-inflammation. As the porcine brain is a plasmalogen-rich resource, this study aimed to explore its potential for plasmalogen-based health food product development, with special attention on whether and how the industrial production processes influence the plasmalogen content and composition. In the present work, plasmalogens from different porcine brain products were investigated using liquid chromatography-tandem mass spectrometry. The results indicated that all the porcine brain products showed abundant total plasmalogens, of which more than 95% were ethanolamine plasmalogen species. Acetone precipitation, ethanol extraction, and drying did not significantly affect the plasmalogen content, whereas repeated freeze-thaw cycles in the production process led to noticeable loss. The chemometric investigation suggested that raw products and glycerophospholipid products exhibited different profiles; furthermore, the concentration step seemed to impact the plasmalogen composition. The nutritional assessment revealed that porcine brain products showed favorable values of multiple indexes, including PUFA/SFA ratio, n-6/n-3 ratio, thrombogenicity index, and unsaturation index, suggesting a health-beneficial value. The current study not only shows the feasibility of producing porcine brain-derived plasmalogens, but also provides possible strategies for developing and quality-controlling dietary plasmalogen supplements and healthcare products.

A Pacific Oyster-Derived Antioxidant, DHMBA, Protects Renal Tubular HK-2 Cells against Oxidative Stress via Reduction of Mitochondrial ROS Production and Fragmentation.

The kidney contains numerous mitochondria in proximal tubular cells that provide energy for tubular secretion and reabsorption. Mitochondrial injury and consequent excessive reactive oxygen species (ROS) production can cause tubular damage and play a major role in the pathogenesis of kidney diseases, including diabetic nephropathy. Accordingly, bioactive compounds that protect the renal tubular mitochondria from ROS are desirable. Here, we aimed to report 3,5-dihydroxy-4-methoxybenzyl alcohol (DHMBA), isolated from the Pacific oyster (Crassostrea gigas) as a potentially useful compound. In human renal tubular HK-2 cells, DHMBA significantly mitigated the cytotoxicity induced by the ROS inducer L-buthionine-(S, R)-sulfoximine (BSO). DHMBA reduced the mitochondrial ROS production and subsequently regulated mitochondrial homeostasis, including mitochondrial biogenesis, fusion/fission balance, and mitophagy; DHMBA also enhanced mitochondrial respiration in BSO-treated cells. These findings highlight the potential of DHMBA to protect renal tubular mitochondrial function against oxidative stress.

Factors Influencing the Indeterminate Results in a T-SPOT.TB test: A Matched Case-control Study.

Objective A T-SPOT.TB can yield indeterminate results under two test observation conditions: a high response to the nil in negative control wells (high nil-control) or a low response to the mitogen in positive control wells (low mitogen-control). The most strongly influential factors for these indeterminate results, however, have yet to be identified. Methods From June 1, 2015, to June 30, 2021, we conducted a 1:1 matched case-control, retrospective study. Patients Patients who underwent a T-SPOT.TB test at Chiba University Hospital. Results The study included 5,956 participants. Indeterminate results were found in 63 participants (1.1%), including high nil-control in 37 and low mitogen-control in 26. Human T-cell leukemia virus type 1 (HTLV-1) positivity was the only influencing factor associated with high nil-control (adjusted odds ratio=98.5, 95% confidence interval: 6.59-1,480). Conclusion Regarding the indeterminate results, all HTLV-1 positive participants had a high nil response and no low mitogen response. It was suspected that abnormally produced interferon γ caused a nonspecific reaction to the negative control well, resulting in a high nil response. Low mitogen-control, conversely, did not appear to have any statistically significant influential factors.

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.

Oxidized Low-Density Lipoproteins Trigger Hepatocellular Oxidative Stress with the Formation of Cholesteryl Ester Hydroperoxide-Enriched Lipid Droplets.

Oxidized low-density lipoproteins (oxLDLs) induce oxidative stress in the liver tissue, leading to hepatic steatosis, inflammation, and fibrosis. Precise information on the role of oxLDL in this process is needed to establish strategies for the prevention and management of non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH). Here, we report the effects of native LDL (nLDL) and oxLDL on lipid metabolism, lipid droplet formation, and gene expression in a human liver-derived C3A cell line. The results showed that nLDL induced lipid droplets enriched with cholesteryl ester (CE) and promoted triglyceride hydrolysis and inhibited oxidative degeneration of CE in association with the altered expression of LIPE, FASN, SCD1, ATGL, and CAT genes. In contrast, oxLDL showed a striking increase in lipid droplets enriched with CE hydroperoxides (CE-OOH) in association with the altered expression of SREBP1, FASN, and DGAT1. Phosphatidylcholine (PC)-OOH/PC was increased in oxLDL-supplemented cells as compared with other groups, suggesting that oxidative stress increased hepatocellular damage. Thus, intracellular lipid droplets enriched with CE-OOH appear to play a crucial role in NAFLD and NASH, triggered by oxLDL. We propose oxLDL as a novel therapeutic target and candidate biomarker for NAFLD and NASH.

Distinctive serum lipidomic profile of IVIG-resistant Kawasaki disease children before and after treatment.

Kawasaki Disease (KD) is an acute inflammatory disorder associated with systemic vasculitis. Intravenous immunoglobulin (IVIG) is an effective therapy for KD, yet, about 20% of cases show IVIG resistance with persistent inflammation. The lipid profile in IVIG-resistant KD patients and the relationship between lipid characteristics and IVIG resistance remain unknown. In this study, serum samples from twenty KD patients with different IVIG responses (sensitive, intermediate, or resistant) were collected both before and after treatment, and lipidomic analysis was performed using high-performance liquid chromatography-mass spectrometry. As a result, before treatment, six lipid species were found as the most variant features, in which all the top decreased lipids in the IVIG-resistant group were lysophosphatidylcholine (LPC) and lysophosphatidylethanolamine (LPE), suggesting the potential to be IVIG-resistant markers in pretreatment diagnosis. During treatment, lipidomic changes showed a weaker response in the IVIG-resistant group. After treatment, LPC and LPE species exhibited lower in the IVIG-resistant group and negative correlation with the inflammatory markers, indicating that the unique metabolism may occur among IVIG-responsiveness. These results might contribute to diagnosing IVIG-resistant patients more accurately for alternative therapy and to a better understanding of how lipid metabolism is associated with IVIG sensitiveness/resistance in KD.

Extraction and Quantitation of Phytosterols from Edible Brown Seaweeds: Optimization, Validation, and Application.

Brown seaweeds are known as important marine food sources, from which phytosterols have been recognized as functional food components with multiple health-beneficial effects. However, studies on phytosterol extraction and quantitation from edible brown seaweeds are limited. In the present work, extraction methods for seaweed phytosterols were compared and optimized by one-factor-at-one-time method and response surface methodology. Moreover, the quantitation method of total sterols and major sterol components, including fucosterol, saringosterol, and ostreasterol, was established and validated using 1H NMR. Furthermore, the developed extraction and determination methods were applied to investigate three common edible seaweeds from Japan (Hijiki, Wakame, and Kombu). As a result, the finally optimized conditions were ultrasound-assisted extraction with CHCl3-MeOH 2:3 for 15 min followed by saponification with 1.65 mL of 1.85 M KOH for 14.5 h. Based on the developed methods, phytosterols in three seaweeds were compared, and Hijiki showed an abundant total sterol amount (2.601 ± 0.171 mg/g DW), significantly higher than Wakame (1.845 ± 0.137 mg/g DW) and Kombu (1.171 ± 0.243 mg/g DW). Notably, the composition of the sterol components varied in different seaweeds. These findings might help the nutritional investigation and functional food development concerning phytosterols from seaweeds.

Serum 25-hydroxyvitamin D3 Levels and Diabetes in a Japanese Population: The DOSANCO Health Study.

BACKGROUND: Both decreased insulin sensitivity and impaired insulin secretion are common in Asian populations with diabetes, in contrast to Western populations. There is limited evidence regarding the association between insulin response in diabetes in Asian populations and serum 25-hydroxyvitamin D3 (25[OH]D3) insufficiency. METHODS: The present cross-sectional study compared the prevalence of diabetes, defined as a fasting plasma glucose level ≥126 mg/dL and/or a HbA1c level ≥6.5%, among 480 participants aged 35-79 years not taking anti-diabetes medications, based on serum 25(OH)D3 levels. A logistic regression model was used to calculate the odds ratios for diabetes in each serum 25(OH)D3 group. Furthermore, this study examined the association between serum 25(OH)D3 levels and the index of homeostasis model assessment of insulin resistance (HOMA-IR) using a linear regression model. RESULTS: The prevalence of diabetes was 7.29% in the study population, and was higher in lower serum 25(OH)D3 quartile groups. The odds ratios for diabetes in the first, second, and third serum 25(OH)D3 quartile groups (25[OH]D3: ≤18.10, 18.11-22.90, and 22.91-28.17 ng/mL) were 4.02 (95% confidence interval [CI], 1.25-12.92), 2.50 (95% CI, 0.77-8.10), and 1.91 (95% CI, 0.60-6.09), respectively, with the fourth quartile group (⩾28.18 ng/mL) serving as the reference group, after adjusting for sociodemographic, lifestyle, physical and environmental factors. Serum 25(OH)D3 levels showed an inverse association with log-transformed HOMA-IR after adjusting for similar factors (standardized ß = -0.08; 95% CI, -0.14 to -0.02). CONCLUSION: Serum 25(OH)D3 levels were inversely associated with diabetes prevalence in a general Japanese population, with a slight inverse association between serum 25(OH)D3 levels and HOMA-IR.

Temporal lipid profiling in the progression from acute to chronic heart failure in mice and ischemic human hearts.

BACKGROUND AND AIMS: Myocardial infarction (MI) is a leading cause of heart failure (HF). After MI, lipids undergo several phasic changes implicated in cardiac repair if inflammation resolves on time. However, if inflammation continues, that leads to end stage HF progression and development. Numerous studies have analyzed the traditional risk factors; however, temporal lipidomics data for human and animal models are limited. Thus, we aimed to obtain sequential lipid profiling from acute to chronic HF. METHODS: Here, we report the comprehensive lipidome of the hearts from diseased and healthy subjects. To induce heart failure in mice, we used a non-reperfused model of coronary ligation, and MI was confirmed by echocardiography and histology, then temporal kinetics of lipids in different tissues (heart, spleen, kidney), and plasma was quantitated from heart failure mice and compared with naïve controls. For lipid analysis in mouse and human samples, untargeted liquid chromatography-linear trap quadrupole orbitrap mass spectrometry (LC-LTQ-Orbitrap MS) was performed. RESULTS: In humans, multivariate analysis revealed distinct cardiac lipid profiles between healthy and ischemic subjects, with 16 lipid species significantly downregulated by 5-fold, mainly phosphatidylethanolamines (PE), in the ischemic heart. In contrast, PE levels were markedly increased in mouse tissues and plasma in chronic MI, indicating possible cardiac remodeling. Further, fold change analysis revealed site-specific lipid biomarkers for acute and chronic HF. A significant decrease in sulfatides (SHexCer (34:1; 2O)) and sphingomyelins (SM (d18:1/16:0)) was observed in mouse tissues and plasma in chronic HF. CONCLUSIONS: Overall, a significant decreased lipidome in human ischemic LV and differential lipid metabolites in the transition of acute to chronic HF with inter-organ communication could provide novel insights into targeting integrative pathways for the early diagnosis or development of novel therapeutics to delay/prevent HF.

Simultaneous free fatty acid elevations and accelerated desaturation in plasma and oocytes in early postpartum dairy cows under intensive feeding management.

A severe negative energy balance and high circulating free fatty acids (FFA) in postpartum cows impair fertility. The lipotoxicity of FFA has been shown to decrease the quality of bovine oocytes in vitro. Therefore, excess FFA in cells is converted to triacylglycerol (TAG), a non-toxic form, to avoid lipotoxicity. We recently reported that the TAG content in oocytes was higher in postpartum lactating cows subjected to grazing management than in heifers (Theriogenology 176: 174-182, 2021). The present study investigated the compositions of the energy metabolism-related lipids, FFA and TAG, in the plasma and oocytes of cows at different lactation stages under indoor intensive feeding management in order to obtain insights into lipotoxicity in oocytes, particularly those in early postpartum cows. Blood and oocytes were collected from 20 lactating cows categorized into the following lactation groups: 20-30 days in milk (DIM) (n = 5), 40-50 DIM (n = 5), 60-80 DIM (n = 5), and 130-160 DIM (n = 5). Daily energy balance data were obtained for 3 weeks prior to oocyte collection using the ovum pick up (OPU) method. The contents and compositions of FFA and TAG in plasma and oocytes were analyzed using liquid chromatography-mass spectrometry. As expected, plasma FFA was high at 20-30 DIM, decreased by 50 DIM, and was maintained at a low level for the remainder of the experimental period. Similar changes were observed in oocyte FFA and TAG with DIM as plasma FFA. Oocyte FFA positively correlated with plasma FFA (P < 0.05), but negatively correlated with the mean energy balance 1 and 21 days before OPU (P < 0.05). Relationships were noted between the composition and content of FFA in plasma and oocytes, with the FFA 16:1/16:0 and 18:1/18:0 ratios positively correlating with the total amount of FFA (P < 0.05). Elevated oocyte FFA in cows in the early postpartum period under intensive feeding management suggested that oocytes were at a high risk of FFA lipotoxicity. Furthermore, the present results implied that the severe negative energy balance in the previous few weeks was closely related to increases in oocyte FFA, which supports the importance of long-term cow feeding management for preserving the quality of oocytes in the early postpartum period. The present results provide insights into the effects of high circulating FFA on the fertility of postpartum cows.

Analysis of Antioxidant Lipids in Five Species of Dietary Seaweeds by Liquid Chromatography/Mass Spectrometry.

Seaweeds are a good source of bioactive lipids and are known for their nutritional benefits, making them a valuable food source. Despite their dietary significance and nutritional importance, there are limited reports on comprehensive lipidome analysis of lipids with antioxidant properties. Therefore, this study aimed to compare the lipid profiles of five commonly consumed Japanese dietary seaweeds using non-targeted liquid chromatography/mass spectrometry (LC/MS). A total, of 304 molecular species from four major lipid classes were detected and characterized by MS/MS analysis. Multivariate statistical analysis revealed distinct lipid molecular compositions in kombu and sea mustard compared to hijiki, mozuku, and laver seaweeds. Kombu has been shown to contain large amounts of antioxidants, such as polyunsaturated fatty acids (PUFAs), and a high health promotion index compared to other seaweeds. Hierarchical cluster correlations indicated the predominance of glycerophospholipids (GPs) and glycerolipids (GLs) in sea mustard and kombu. As a result, dietary seaweeds have great potential as antioxidants and health-promoting foods for human consumption due to their high levels of PUFA-rich GPs and GLs. Unsaturated triacylglycerols are predominant in hijiki, whereas other health-beneficial lipids, such as monogalactosyldiacylglycerol and sulfoquinovosyl diacylglycerols, are predominant in sea mustard. This study provides a detailed characterization of lipids and their comparative fingerprints in seaweeds, demonstrating the potential use of dietary seaweeds in biotechnological and industrial applications involving the development of functional food products.