Phosphorus(Pi)plays a crucial role in the growth and development of plants.Membrane lipid regulation is one of the main mechanisms underlying plant adaptation to Pi deficiency.Previously,the high tolerance to low-Pi s...Phosphorus(Pi)plays a crucial role in the growth and development of plants.Membrane lipid regulation is one of the main mechanisms underlying plant adaptation to Pi deficiency.Previously,the high tolerance to low-Pi stress was justified in an elite line,MSDZ 109,which was obtained from Malus mandshurica.To better understand the mechanism underlying high adaptation to low-Pi stress,currently,lipidomic and transcriptomic analysis,as well as CRISPR/Cas9 and MmGDPD1-overexpressing methodologies were comprehensively integrated into a strategy for elucidating the high tolerance to low-Pi stress.Totally,770 differential metabolites were identified from the roots between the low-Pi and stress-free,belonging to 21 sub-classes of lipid compounds.Fatty acids(FA)constituted the predominant lipid component,accounting for approximately 50%-60%of the total lipids,and triglycerides(TAG)ranked the second,comprising around 12%of the total,consecutively followed by phosphatidylcholine(PC)and diacylglycerol(DAG)with approximately 10%and 8%of the total,respectively.The synchronous transcriptomic analysis revealed a significant up-regulation of genes related to glycerophospholipid and glycerolipid metabolism,specifically those(e.g.,MmGDPD1,MmDGDG1,MmMGDG1,MmSQDG,etc.)involved in phospholipid and galactosyl synthesis in response to low-Pi stress.GUS fusing reporter assay showed that MmGDPD1 promoter induced GUS gene expression and demonstrated initiation activity.Based on expression analysis,a dual-luciferase reporter assay,as well as yeast one-hybrid(Y1H)identification,MmPHR1 was justified to bind with the MmGDPD1 promoter and positively regulate plant tolerance to low-Pi stress.To further elucidate the role of MmGDPD1,CRISPR/Cas9 and MmGDPD1-overexpressing vectors were successfully introduced into apple(‘Royal Gala')calli.Interestingly,the MmGDPD1-KO line calli exhibited the remarkable decreases in the contents of phosphodiesterase(PDE),activity,as well as the contents of total Pi,and Pi in comparison with those of the wild type.Conversely,MmGDPD1-OE ones demonstrated the significant elevation in Pi accumulations,further justifying its potential role in Pi remobilization in apple.Therefore,MmGDPD1 substantially involves elevating low-Pi tolerance via promoting Pi release in M.mandshurica.展开更多
Background In contrast to protein-rich insect meal,the feed potential of insect fat is generally less explored and knowledge about the suitability of insect fat as a fat source specifically in broiler diets is still l...Background In contrast to protein-rich insect meal,the feed potential of insect fat is generally less explored and knowledge about the suitability of insect fat as a fat source specifically in broiler diets is still limited.In view of this,the present study aimed to comprehensively investigate the effect of partial(50%) and complete replacement of soybean oil with insect fat from Hermetia illucens(HI) larvae in broiler diets on performance,fat digestibility,cecal microbiome,liver transcriptome and liver and plasma lipidomes.Thus,100 male,1-day-old Cobb 500 broilers were randomly assigned to three groups and fed three different diets with either 0(group HI-0,n cens(HI) larvae fat for 35 d.= 30),2.5%(group HI-2.5,n %(HI-5.0,n = 35) or 5.0= 35) Hermetia illuResults Body weight gain,final body weight,feed intake,and feed:gain ratio during the whole period and apparent ileal digestibility coefficient for ether extract were not different between groups.Cecal microbial diversity did not differ between groups and taxonomic analysis revealed differences in the abundance of only four low-abundance bacterial taxa among groups;the abundances of phylum Actinobacteriota,class Coriobacteriia,order Coriobacteriales and family Eggerthellaceae were lower in group HI-5.0 compared to group HI-2.5(P < 0.05).Concentrations of total and individual short-chain fatty acids in the cecal digesta were not different between the three groups.Liver transcriptomics revealed a total of 55 and 25 transcripts to be differentially expressed between groups HI-5.0 vs.HI-0 and groups HI-2.5 vs.HI-0,respectively(P < 0.05).The concentrations of most lipid classes,with the exception of phosphatidylethanolamine,phosphatidylglycerol and lysophosphatidylcholine in the liver and cholesterylester and ceramide in plasma(P < 0.05),and of the sum of all lipid classes were not different between groups.Conclusions Partial and complete replacement of soybean oil with HI larvae fat in broiler diets had no effect on growth performance and only modest,but no adverse effects on the cecal microbiome and the metabolic health of broilers.This suggests that HI larvae fat can be used as an alternative fat source in broiler diets,thereby,making broiler production more sustainable.展开更多
Drug-associated reward memories are conducive to intense craving and often trigger relapse.Simvastatin has been shown to regulate lipids that are involved in memory formation but its influence on other cognitive proce...Drug-associated reward memories are conducive to intense craving and often trigger relapse.Simvastatin has been shown to regulate lipids that are involved in memory formation but its influence on other cognitive processes is elusive.Here,we used a mass spectrometry-based lipidomic method to evaluate the impact of simvastatin on the mouse brain in a cocaine-induced reinstatement paradigm.We found that simvastatin blocked the reinstatement of cocaine-induced conditioned place preference(CPP)without affecting CPP acquisition.Specifically,only simvastatin administered during extinction prevented cocaine-primed reinstatement.Global lipidome analysis showed that the nucleus accumbens was the region with the greatest degree of change caused by simvastatin.The metabolism of fatty-acids,phospholipids,and triacylglycerol was profoundly affected.Simvastatin reversed most of the effects on phospholipids induced by cocaine.The correlation matrix showed that cocaine and simvastatin significantly reshaped the lipid metabolic pathways in specific brain regions.Furthermore,simvastatin almost reversed all changes in the fatty acyl profile and unsaturation caused by cocaine.In summary,pre-extinction treatment with simvastatin facilitates cocaine extinction and prevents cocaine relapse with brain lipidome remodeling.展开更多
Calcium(Ca^(2+))plays an important role in determining plant growth and development because it maintains cell wall and membrane integrity.Therefore,understanding the role of Ca^(2+)in carbon and lipid metabolism could...Calcium(Ca^(2+))plays an important role in determining plant growth and development because it maintains cell wall and membrane integrity.Therefore,understanding the role of Ca^(2+)in carbon and lipid metabolism could provide insights into the dynamic changes in cell membranes and cell walls during the rapid elongation of cotton fibers.In the present study,we found that the lack of Ca^(2+)promoted fiber elongation and rapid ovule expansion,but it also caused tissue browning in the ovule culture system.RNA-sequencing revealed that Ca^(2+)deficiency induced cells to be highly oxidized,and the expression of genes related to carbon metabolism and lipid metabolism was activated significantly.All gene members of nine key enzymes involved in glycolysis were up-regulated,and glucose was significantly reduced in Ca^(2+)deficiency-treated tissues.Ca^(2+)deficiency adjusted the flowing of glycolysis metabolic.However,low K^(+)recovered the expression levels of glycolysis genes and glucose content caused by Ca^(2+)deficiency.Electrospray ionizationtandem mass spectrometry technology was applied to uncover the dynamic profile of lipidome under Ca^(2+)and K^(+)interacted conditions.Ca^(2+)deficiency led to the decrease of fatty acid(FA),diacylglycerol(DAG),glycolipid and the significant increase of triacylglycerol(TAG),phospholipid phosphatidylethanolamine(PE),phosphatidylglycerol(PG),and PC(phosphatidylcholine).Low K^(+)restored the contents of FA,phospholipids,and glycolipids,effectively relieved the symptoms caused by Ca^(2+)deficiency,and recovered the development of fiber cells.This study revealed dynamic changes in transcript and metabolic levels and uncovered the signaling interaction of Ca^(2+)deficiency and low K^(+)in glycolysis and lipid metabolism during fiber development.展开更多
The term lipidome is mentioned to the total amount of the lipids inside the biological cells.The lipid enters the human gastrointestinal tract through external source and internal source.The absorption pathway of lipi...The term lipidome is mentioned to the total amount of the lipids inside the biological cells.The lipid enters the human gastrointestinal tract through external source and internal source.The absorption pathway of lipids in the gastrointestinal tract has many ways;the 1st way,the lipid molecules are digested in the lumen before go through the enterocytes,digested products are re-esterified into complex lipid molecules.The 2nd way,the intracellular lipids are accumulated into lipoproteins(chylomicrons)which transport lipids throughout the whole body.The lipids are re-synthesis again inside the human body where the gastrointestinal lipids are:(1)Transferred into the endoplasmic reticulum;(2)Collected as lipoproteins such as chylomicrons;or(3)Stored as lipid droplets in the cytosol.The lipids play an important role in many stages of the viral replication cycle.The specific lipid change occurs during viral infection in advanced viral replication cycle.There are 47 lipids within 11 lipid classes were significantly disturbed after viral infection.The virus connects with blood-borne lipoproteins and apolipoprotein E to change viral infectivity.The viral interest is cholesterol-and lipid raft-dependent molecules.In conclusion,lipidome is important in gastrointestinal fat absorption and coronavirus disease 2019(COVID-19)infection so lipidome is basic in gut metabolism and in COVID-19 infection success.展开更多
Lipidomics coverage improvement is essential for functional lipid and pathway construction.A powerful approach to discovering organism lipidome is to combine various data acquisitions,such as full scan mass spectromet...Lipidomics coverage improvement is essential for functional lipid and pathway construction.A powerful approach to discovering organism lipidome is to combine various data acquisitions,such as full scan mass spectrometry(full MS),data-dependent acquisition(DDA),and data-independent acquisition(DIA).Caenorhabditis elegans(C.elegans)is a useful model for discovering toxic-induced metabolism,highthroughput drug screening,and a variety of human disease pathways.To determine the lipidome of C.elegans and investigate lipid disruption from the molecular level to the system biology level,we used integrative data acquisition.The methyl-tert-butyl ether method was used to extract L4 stage C.elegans after exposure to triclosan(TCS),perfluorooctanoic acid,and nanopolystyrene(nPS).Full MS,DDA,and DIA integrations were performed to comprehensively profile the C.elegans lipidome by Q-Exactive Plus MS.All annotated lipids were then analyzed using lipid ontology and pathway analysis.We annotated up to 940 lipids from 20 lipid classes involved in various functions and pathways.The biological investigations revealed that when C.elegans were exposed to nPS,lipid droplets were disrupted,whereas plasma membrane-functionalized lipids were likely to be changed in the TCS treatment group.The nPS treatment caused a significant disruption in lipid storage.Triacylglycerol,glycerophospholipid,and ether class lipids were those primarily hindered by toxicants.Finally,toxicant exposure frequently involved numerous lipid-related pathways,including the phosphoinositide 3-kinase/protein kinase B pathway.In conclusion,an integrative data acquisition strategy was used to characterize the C.elegans lipidome,providing valuable biological insights into hypothesis generation and validation.展开更多
The tear film covers the anterior eye and the precise balance of its various constituting components is critical for maintaining ocular health.The composition of the tear film amphiphilic lipid sublayer,in particular,...The tear film covers the anterior eye and the precise balance of its various constituting components is critical for maintaining ocular health.The composition of the tear film amphiphilic lipid sublayer,in particular,has largely remained a matter of contention.The limiting concentrations of lipid amphiphiles in tears have also posed considerable challenges to their detection and accurate quantitation.Using systematic and sensitive lipidomic approaches,we reported the most comprehensive human tear lipidome to date;and conferred novel insights to the compositional details of the existent tear film model,in particular the disputable amphiphilic lipid sublayer constituents,by demonstrating the presence of cholesteryl sulfate,O-acyl-ω-hydroxy fatty acids,and various sphingolipids and phospholipids in tears.Lipidomic analysis of human tear fluid from patients with various subtypes of dry eye syndrome(DES)revealed structure-specific lipid alterations in DES,which could potentially serve as unifying indicators of disease symptoms and signs.The meibomian glands constitute the predominant source of lipid supply to the human tear fluid.Meibomian gland dysfunction(MGD)is a leading cause of evaporative dry eye and ocular discomfort,characterized by an unstable tear film principally attributed to afflicted delivery of lipids to the ocular surface.We investigated the longitudinal tear lipid alterations associated with disease alleviation and symptom improvement in a cohort of MGD patients undergoing eyelid-warming treatment for 12 weeks.Our preliminary data indicated that excess ocular surface phospholipase activity detrimental to tear film stability could be alleviated by eyelid warming alone without application of steroids and identify tear OAHFAs as suitable markers to monitor treatment response in MGD.展开更多
Sacoglossan sea slugs have attracted considerable scientific attention due to their capacity to retain functional macroalgal chloroplasts inside their cells.This endosymbiotic association is nutritionally relevant for...Sacoglossan sea slugs have attracted considerable scientific attention due to their capacity to retain functional macroalgal chloroplasts inside their cells.This endosymbiotic association is nutritionally relevant for these organisms and represents an interesting research issue for biotechnological applications.The Caribbean species Elysia crispata can integrate chloroplasts from different macroalgal species.The lipidome of chloroplasts includes lipid classes unique to these photosynthetic organelles.Specialized lipids,such as the glycolipids MGDG,DGDG,and SQDG,are essential for maintaining the integrity of both the thylakoid membranes and the overall chloroplast membrane structure.Additionally,lipids are a diverse group of biomolecules playing essential roles at nutritional and physiological levels.A combined approach using LC–HR-MS and MS/MS was employed to determine the polar lipid profile of the photosynthetic sea slug E.crispata from two habitats in the north-western tropical Atlantic(Sistema Arrecifal Veracruzano and Mahahual)and two different feeding conditions(fed and after 1 week of starvation).Significant differences were identified in the abundance of structural and signalling phospholipids(PC,PI,PG,PS,CL)suggesting different nutritional states between populations.The composition of glycolipids demonstrated a clear separation by habitat,but not by feeding conditions.The lower abundance of glycolipids in the Mahahual samples suggests a lower density of chloroplasts in their tissues compared to Veracruz individuals.These results corroborate that 1 week of starvation is insufficient to initiate the degradation of plastid membranes.This study confirms the advantages of using lipidomics as a tool to enhance our knowledge of the ecology of marine invertebrates.展开更多
The hadal zone environment,characterized by extreme hydrostatic pressure,low temperatures,and limited food availability,presents substantial survival challenges for deep-sea fish species.In this study,we captured five...The hadal zone environment,characterized by extreme hydrostatic pressure,low temperatures,and limited food availability,presents substantial survival challenges for deep-sea fish species.In this study,we captured five deepsea fish species(Bathysaurus mollis,Coryphaenoides rudis,Ilyophis sp.,I.brunneus and Pseudoliparis swirei)from the Mariana Trench at depths ranging from 2027 to 7125 m,by employing China's“Exploration I and Exploration II”.By combining lipidomic and proteomic analyses,we aimed to explore the genetic basis of adaptive evolution to the hadal zone in fish.The results indicate several key findings:(1)P.swirei(Mariana hadal snailfish,MHS)may enhance energy storage and utilization during prolonged fasting periods by significantly increasing liver tissue levels of cholesterol ester(CE),ether-linked triacylglycerol(TG-O),coenzyme Q(CoQ),and ATPase content;(2)MHS could maintain membrane fluidity under high pressure by increasing the proportion of unsaturated fatty acids while reducing levels of cholesterol and phosphatidylethanolamine(PE)content.(3)The regulation of lipid types and ratios could increase the risk of lipid peroxidation.To counter oxidative stress,MHS likely elevates monounsaturated fatty acid content and enhances antioxidants such as transferrin and heat shock proteins.Overall,this study provides new insights into the adaptive mechanisms of MHS to deep-sea conditions through the lipidome and proteome analyses,thus broadening our understanding of its resilience in the hadal zone.展开更多
Lipid metabolism is very important for meat quality in pigs.Accumulating evidence shows that gut microbiota can contribute to this physiological process.However,the gut microbiota that function in lipid metabolism and...Lipid metabolism is very important for meat quality in pigs.Accumulating evidence shows that gut microbiota can contribute to this physiological process.However,the gut microbiota that function in lipid metabolism and adipogenesis remains unclear.Here,we compared the characteristics of fat deposition and gut microbial community between Laiwu pigs and Duroc(LandraceYorkshire)(DLY)pigs.Fecal microbiota transplantation(FMT)was performed to determine the possible impact of gut microbiota on lipid metabolism in pigs.An integrated analysis of the gut microbiome and lipidome of the small intestine,plasma,and liver was conducted to investigate the effects of FMT on host lipid metabolism.The comparative analysis of the gut microbiome showed higher abundance of Bacteroidetes(P=0.0018)while lower abundance of Firmicutes(P=0.012)in Laiwu pigs,and the microbial composition can be transferred from Laiwu pigs into DLY pigs.Transmission electron microscope and Oil red-O staining were performed to analyze the effects of FMT on lipid deposition in liver,the main target organ for lipid metabolism.The results showed that FMT significantly increased the number of lipid droplets(P=0.0035)and lipid accumulation(P=0.0026)in liver.Furthermore,integrated multi-tissues lipidome analysis demonstrated that the fatty acyls and glycerophospholipids were significantly increased(P<0.01)in intestine and liver,while glycerolipids and fatty acyls were reduced(P<0.01)in plasma.In the small intestine,FMT increased(P<0.01)the relative abundance of polyketides and prenol lipids but reduced(P<0.01)the saccharolipids.Correlation analysis revealed the potential interactions between microbiota and lipid metabolites.Together,our results indicated that the gut microbiota may regulate the lipid metabolism and enhance the accumulation of lipid droplets in the liver of pigs.展开更多
Background:Sargentodoxae Caulis(SC)is the vine stem of Sargentodoxa Cuneata(Oliv.)Rehd.&E.H.Wilson in C.S.Sargent,and it in traditional Chinese medicine has been known for promoting blood circulation and removing ...Background:Sargentodoxae Caulis(SC)is the vine stem of Sargentodoxa Cuneata(Oliv.)Rehd.&E.H.Wilson in C.S.Sargent,and it in traditional Chinese medicine has been known for promoting blood circulation and removing blood stasis as recorded in the ancient book“Illustrated Classics of Materia Medica”.It has been used effectively to treat blood stasis too in modern clinical practice.However,the anti-hyperlipidemia effect of SC is not fully understood.This paper aims at exploring the use of SC stems to improve the balance of blood lipids in the body,and its new role in treating hyperlipidemia.Methods:The effects of SC extract on hyperlipidemia were explored by combining lipidomics and gut microbiota.Secondly,we explored the potential mechanism of SC in treating hyperlipidemia by pathway analysis.Results:The results showed that the stem extract of SC could restore the physiological and biochemical indices of hyperlipidemia in mice,as well as repair the morphological and structural damage to tissues.Compared to the Model group,the SC extract significantly reduced the liver index,epididymal fat index,and Lee’s index.It also significantly decreased serum levels of total cholesterol,triglycerides,low-density lipoprotein cholesterol,peroxisome proliferator-activated receptor gamma(PPAR-γ),D-lactate,and free fatty acids,while significantly increasing the relative content of peroxisome proliferator-activated receptor alpha(PPAR-α).These changes were statistically significant.Non-targeted lipidomics,based on LC-MS,were utilized to investigate the lipid metabolism characteristics in serum,liver,and epididymal fat of the subjects.It was observed that,compared to the blank group,the Model group exhibited significant changes primarily in glycerol lipids and glycerophospholipids.The treatment group also displayed alterations in these lipids.A total of 38,81,and 27 differential lipids were identified in serum,liver,and epididymal fat samples,respectively.Among these,14 common differential lipids were found in both serum and liver samples,and their KEGG enrichment pathways were largely consistent.Among them,the sphingolipid signaling pathway and the glycerophospholipid metabolic pathway were identified as key metabolic pathways that were regulated.Our gut microbiota analysis revealed that SC diminishes the abundance of Actinobacteria by altering the cecal flora in mice.Conclusion:This alteration leads to the downregulation of genes involved in triglyceride metabolism,which in turn changes lipid processing and reduces triglyceride levels.Consequently,SC effectively combats hyperlipidemia.Notably,SC impacts key metabolic pathways,including the sphingolipid signaling and glycerophospholipid metabolism.These findings underscore SC’s therapeutic potential,positioning it as a promising alternative for reducing the health risks associated with hyperlipidemia.展开更多
Varicocele(VC)is a common cause of male infertility,yet there is a lack of molecular information for VC-associated male infertility.This study investigated alterations in the seminal plasma metabolomic and lipidomic p...Varicocele(VC)is a common cause of male infertility,yet there is a lack of molecular information for VC-associated male infertility.This study investigated alterations in the seminal plasma metabolomic and lipidomic profiles of infertile male VC patients.Twenty infertile males with VC and twenty-three age-matched healthy controls(HCs)were recruited from Peking Union Medical College Hospital(Beijing,China)between October 2019 and April 2021.Untargeted metabolite and lipid profiles from seminal plasma were analyzed using mass spectrometry.Four hundred and seventy-six metabolites and seventeen lipids were significantly different in infertile male VC patients compared to HCs.The top enriched pathways among these significantly different metabolites are protein digestion and absorption,aminoacyl-transfer RNA(tRNA)biosynthesis,and biosynthesis of amino acids.Different key lipid species,including triglyceride(TG),diacylglycerol(DG),ceramides(Cer),and phosphatidylserine(PS),varied betweenVC and HC groups.The distinct metabolites and lipids were moderately correlated.DL-3-phenyllactic acid is a potential diagnostic biomarker for VC-related male infertility(area under the curve[AUC]=0.893),positively correlating with sperm count,concentration,and motility.Furthermore,DL-3-phenyllactic acid is the only metabolite shared by all four comparisons(VC vs HC,VC-induced oligoasthenospermia[OAS]vs VC-induced asthenospermia[AS],OAS vs HC,and AS vs HC).DL-3-phenyllactic acid significantly decreased in OAS than AS.Metabolite-targeting gene analysis revealed carbonic anhydrase 9(CA9)might be the strongest candidate associated with the onset and severity of VC.The seminal plasma metabolite and lipid profiles of infertile males with VC differ significantly from those of HCs.DL-3-phenyllactic acid could be a promising biomarker.展开更多
Astragali Radix(AR), a traditional Chinese medicine(TCM), has demonstrated therapeutic efficacy against various diseases, including cardiovascular conditions, over centuries of use.While doxorubicin serves as an effec...Astragali Radix(AR), a traditional Chinese medicine(TCM), has demonstrated therapeutic efficacy against various diseases, including cardiovascular conditions, over centuries of use.While doxorubicin serves as an effective chemotherapeutic agent against multiple cancers, its clinical application remains constrained by significant cardiotoxicity. Research has indicated that AR exhibits protective properties against doxorubicin-induced cardiomyopathy(DIC);however, the specific bioactive components and underlying mechanisms responsible for this therapeutic effect remain incompletely understood. This investigation seeks to identify the protective bioactive components in AR against DIC and elucidate their mechanisms of action.Through network medicine analysis, astragaloside Ⅳ(AsⅣ) and formononetin(FMT) were identified as potential cardioprotective agents from 129 AR components. In vitro experiments using H9c2 rat cardiomyocytes revealed that the AsⅣ-FMT combination(AFC) effectively reduced doxorubicin-induced cell death in a dose-dependent manner, with optimal efficacy at a 1∶2 ratio. In vivo, AFC enhanced survival rates and improved cardiac function in both acute and chronic DIC mouse models. Additionally, AFC demonstrated cardiac protection while maintaining doxorubicin's anti-cancer efficacy in a breast cancer mouse model. Lipidomic and metabolomics analyses revealed that AFC normalized doxorubicin-induced lipid profile alterations, particularly by reducing fatty acid accumulation. Gene knockdown studies and inhibitor experiments in H9c2 cells demonstrated that AsⅣ and FMT upregulated peroxisome proliferator activated receptor γ coactivator 1α(PGC-1α) and PPARα, respectively, two key proteins involved in fatty acid metabolism. This research establishes AFC as a promising therapeutic approach for DIC, highlighting the significance of multi-target therapies derived from natural herbals in contemporary medicine.展开更多
Background:Elucidating mechanisms underlying atrial myopathy,which predisposes individuals to atrial fibrillation(AF),will be critical for preventing/treating AF.In a serendipitous discovery,we identified atrial enlar...Background:Elucidating mechanisms underlying atrial myopathy,which predisposes individuals to atrial fibrillation(AF),will be critical for preventing/treating AF.In a serendipitous discovery,we identified atrial enlargement,fibrosis,and thrombi in mice with reduced phosphoinositide 3-kinase(PI3K)in cardiomyocytes.PI3K(p110a)is elevated in the heart with exercise and is critical for exercise-induced ventricular enlargement and protection,but the role in the atria was unknown.Physical inactivity and extreme endurance exercise can increase AF risk.Therefore,our objective was to investigate whether too little and/or too much PI3K alone induces cardiac pathology.Methods:New cardiomyocyte-specific transgenic mice with increased or decreased PI3K(p110a)activity were generated.Multi-omics was conducted in mouse atrial tissue,and lipidomics in human plasma.Results:Elevated PI3K led to an increase in heart size with preserved/enhanced function.Reduced PI3K led to atrial dysfunction,fibrosis,arrhythmia,increased susceptibility to atrial enlargement and thrombi,and dysregulation of monosialodihexosylganglioside(GM3),a lipid that regulates insulin-like growth factor-1(IGF1)-PI3K signaling.Proteomic profiling identified distinct signatures and signaling networks acrossatria with varying degrees of dysfunction,enlargement,and thrombi,including commonalities with the human AF proteome.PI3K-related lipids were dysregulated in plasma from athletes with AF.Conclusion:PI3K(p110a)is a critical regulator of atrial biology and function in mice.This work provides a proteomic resource of candidates for further validation as potential new drug targets and biomarkers for atrial myopathy.Further investigation of PI3K-related lipids as markers for identifying individuals at risk of AF is warranted.Dysregulation of PI3K may contribute to the association between increased cardiac risk with physical inactivity and extreme endurance exercise.展开更多
Objective To reveal the therapeutic effects of moxibustion in collagen-induced arthritis(CIA)rat models using the combined analysis of plasma and synovial membrane lipidomic profil-ing and to enhance the understanding...Objective To reveal the therapeutic effects of moxibustion in collagen-induced arthritis(CIA)rat models using the combined analysis of plasma and synovial membrane lipidomic profil-ing and to enhance the understanding of how moxibustion affects lipid metabolism in rheumatoid arthritis(RA).Methods A total of 32 male Sprague-Dawley(SD)rats were randomly assigned to four groups:control,moxibustion control(MC),model,and moxibustion model(MM)groups,with 8 rats in each group.CIA was induced in SD rats by two immunizations.The paw volume was mea-sured before the induction of CIA.Following induction,after assessing paw volume and arthritis index(AI)scores,the MC and MM groups received treatment at bilateral Shenshu(BL23)and Zusanli(ST36)acupoints for 10 min per acupoint.The intervention included three treatment courses,each spanning 6 d and followed by a 1-d interval.Paw volume and AI scores were assessed after each treatment course.After the completion of the three treatment courses,serum,plasma,synovial tissue,and ankle joint samples were collected.Enzyme-linked immunosorbent assay(ELISA)was employed to quantify the levels of interleukin(IL)-6 and tumor necrosis factor(TNF)-αin serum.Hematoxylin and eosin(HE)staining was per-formed for histopathological examination of the ankle joint tissues.Meanwhile,ultra-high-performance liquid chromatography coupled with Q-Exactive Orbitrap mass spectrometry(UHPLC-Q-Exactive Orbitrap MS)was utilized to analyze the plasma and synovial tissue sam-ples.In addition,multivariate statistical analysis was performed to identify differential lipid metabolites,and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analysis was applied to explore metabolic pathways modulated by moxibustion therapy.Results No significant difference in hind paw volume and AI scores was observed among the groups(P>0.05).After CIA induction,model group showed increased hind paw volume and AI scores compared with control group(P<0.05),which were significantly reduced after mox-ibustion treatment in MM group compared with model group(P<0.05).The levels of IL-6 and TNF-αwere significantly higher in model and MM groups compared with control group(P<0.05),but were lower in MM group than those in model group(P<0.05).Histopathologi-cal analysis showed improved cartilage and reduced inflammation in MM group.A total of 33 differential lipid metabolites in the plasma and 24 in the synovial membranes of CIA rat mod-els were identified when compared with control group.Among these lipid metabolites,31 in the plasma and all 24 in the synovial membranes were regulated by moxibustion treatment.Pathological analysis revealed upregulation of diacylglycerol(DG)and fatty acid(FA)levels,alongside downregulation of lysophosphatidylcholine(LPC),phosphatidylcholine(PC),and phosphatidylethanolamine(PE).Under physiological conditions,the treatment specifically reduced LPC and PC levels.Pathway enrichment analysis revealed that moxibustion predom-inantly affectedα-linolenic acid,glycerophospholipid,and sphingolipid metabolism under pathological conditions.Under physiological conditions,the regulation was centered aroundα-linolenic acid and glycerophospholipid metabolism.Conclusion The RA rat models exhibited significant lipid metabolic disturbances.Moxibus-tion alleviated paw swelling,reduced AI scores,modulated inflammatory cytokine levels,and partially corrected the altered levels of multiple lipid metabolites.The potential metabolic pathways implicated in the regulation of lipid metabolism under both physiological and pathological conditions includeα-linolenic acid,glycerophospholipid,and sphingolipid metabolism.展开更多
Inoculated fermentation enables rapid fermentation of aquatic products.No studies have been conducted on the lipid profiles of inoculated fermented golden pompano(Trachinotus ovatus).In this study,a lipase-producing B...Inoculated fermentation enables rapid fermentation of aquatic products.No studies have been conducted on the lipid profiles of inoculated fermented golden pompano(Trachinotus ovatus).In this study,a lipase-producing Bacillus subtilis with salt tolerance was screened from traditionally fermented golden pompano(TF)and used as a starter culture.Whole-genome sequencing analysis revealed it carries 4 clustered regularly interspaced short vpalindromic repeats structures and 2 genes encoding triacylglycerol lipase.Untargeted lipidomics identified lipid molecules(833)in 6 major classes from B.subtilis SCSMX-2 fermented golden pompano(IF).A total of 28 lipid molecules were upregulated in IF,including phosphatidylcholines(PCs),triacylglycerols(TAGs),and lysophosphatidylcholine.B.subtilis supplementation enhanced the production of polyenyl PCs and mediumand long-chain TAGs.The IF rich in linoleic,docosahexaenoic acids(DHA),and eicosapentaenoic acid were primarily distributed in the sn-2 position of DHA,PC and phosphatidylethanolamine.This research revealed the lipid profiles of IF,providing theoretical basis for the application of B.subtilis in the fermented fish industry.展开更多
Royal jelly(RJ)is rich in various nutrients with multiple health-promoting properties.This study aims to evaluate whether RJ can modulate related metabolite in the natural aging mice.Male C57BL/6J mice drank RJ soluti...Royal jelly(RJ)is rich in various nutrients with multiple health-promoting properties.This study aims to evaluate whether RJ can modulate related metabolite in the natural aging mice.Male C57BL/6J mice drank RJ solution daily for 9 months.Determination of serum lipids and pathological analysis exhibited that triglycerides,serum cholesterol,and low-density lipoprotein cholesterol were decreased by 31.15%,9.96%,and 22.58%,respectively,the morphology of brain nerve cells was also effectively recovered after RJ intervention.Lipidomic analysis showed that RJ could improve the levels of different kinds of lipids in aging mice brain,especially by increasing the content of antioxidant ether ester,and that the ratio of monounsaturated fatty acid to polyunsaturated fatty acid was up by 23.46%,which could alleviate oxidative stress.Moreover,the metabolism of glycerol phospholipids,glycerols,and fatty acids in aging mice could be regulated by RJ.RJ intervention can effectively improve lipid metabolism disorders caused by aging.展开更多
Objective Lipid oxidation is involved in the pathogenesis of atherosclerosis and may be contribute to the development of Ischemic stroke(IS).However,the lipid profiles associated with IS have been poorly studied.We co...Objective Lipid oxidation is involved in the pathogenesis of atherosclerosis and may be contribute to the development of Ischemic stroke(IS).However,the lipid profiles associated with IS have been poorly studied.We conducted a pilot study to identify potential IS-related lipid molecules and pathways using lipidomic profiling.Methods Serum lipidomic profiling was performed using LC-MS in 20 patients with IS and 20 age-and sex-matched healthy controls.Univariate and multivariate analyses were simultaneously performed to identify the differential lipids.Multiple testing was controlled for using a false discovery rate(FDR)approach.Enrichment analysis was performed using MetaboAnalyst software.Results Based on the 294 lipids assayed,principal component analysis(PCA)and orthogonal partial least squares discriminant analysis(OPLS-DA)models were used to distinguish patients with IS from healthy controls.Fifty-six differential lipids were identified with an FDR-adjusted P less than 0.05 and variable influences in projection(VIP)greater than 1.0.These lipids were significantly enriched in glycerophospholipid metabolism(FDR-adjusted P=0.009,impact score=0.216).Conclusions Serum lipid profiles differed significantly between patients with IS and healthy controls.Thus,glycerophospholipid metabolism may be involved in the development of IS.These results provide initial evidence that lipid molecules and their related metabolites may serve as new biomarkers and potential therapeutic targets for IS.展开更多
There is no safe level of exposure to air pollution,including particulate matter smaller than2.5μm(PM_(2.5)),to human health.Whilst it is well known that exposure to heavily polluted air is associated with several li...There is no safe level of exposure to air pollution,including particulate matter smaller than2.5μm(PM_(2.5)),to human health.Whilst it is well known that exposure to heavily polluted air is associated with several liver disorders,it is unclear how long-term exposure to lowlevel traffic-derived PM_(2.5)affects liver health.BALB/c mice(5 weeks,male)were exposed to traffic-derived PM_(2.5)(10μg/mouse/day,intranasally)daily for 4,8 and 12 weeks.Markers of inflammation and fibrosis were measured at each time point.Changes in liver proteome and lipid profiles were measured using proteomics and lipidomics at 12 weeks.Low-dose PM_(2.5)exposure increased macrophage infiltration,pro-inflammatory cytokine production,and increased collagen deposition at 12 weeks.Despite liver lipid metabolism being increased,the abundance of triglycerides,precursor diacylglycerols,and ceramide was also significantly increased by PM_(2.5)exposure,whereas glycogen content was reduced.Proteomics analysis revealed 64 proteins to be significantly changed in PM_(2.5)-exposed mice,and KEGG pathway enrichment analysis indicated their involvement in lipid metabolism,alcohol-related liver disease,neutrophil extracellular trap formation,and transcriptional dysregulation related to cancer.In conclusion,prolonged exposure to low-dose traffic-derived PM_(2.5)promotes pathological changes in the liver,suggestive of an increased risk of metabolic dysfunctionassociated fatty liver disease.Future studies can enable the identification of the signalling pathways underlying low-dose PM_(2.5)-induced lipid accumulation in the liver.展开更多
Background:Developmental dysplasia of the hip(DDH)is a prevalent pediatric condition with a multifactorial etiology.Its incidence varies geographically,with notably higher rates observed on the Xizang plateau.This stu...Background:Developmental dysplasia of the hip(DDH)is a prevalent pediatric condition with a multifactorial etiology.Its incidence varies geographically,with notably higher rates observed on the Xizang plateau.This study was performed to evaluate the lipidomics signatures associated with DDH by analyzing plasma samples.Methods:Fifty infants were recruited,including 25 diagnosed with DDH and 25 age-matched healthy controls.In addition to plasma samples,comprehensive laboratory test results and medical records were collected for each participant.An untargeted lipidomics profiling approach was employed to identify distinguishing metabolic signatures.Results:Lipidomics profiles differed significantly between patients with DDH and healthy controls.Several differential metabolites were identified,including triacylglycerol(TAG)(17:0/18:1/20:1),TAG(17:0/17:0/17:0),phosphatidylethanolamine(PE)(10:0/26:4),TAG(17:0/18:0/18:0),TAG(16:0/17:0/22:1),TAG(16:0/18:0/22:0),TAG(17:0/19:0/19:0),TAG(13:0/20:0/20:0),TAG(18:0/18:0/22:0),and TAG(16:0/20:0/20:0).The primary lipid species showing differences were TAGs and PE.Conclusions:Distinct shifts in lipidomics profiles were observed in infants with DDH.To the best of our knowledge,this study is the first to explore lipidomics signatures in patients with DDH.The combined assessment of TAG(17:0/18:1/20:1)and TAG(17:0/17:0/17:0)may serve as a potential diagnostic tool for DDH.展开更多
基金supported by grants from the National Guidance Foundation for Local Science and Technology Development of China(Grant No.2023-009)the Department of Science and Technology of Guizhou Province(Grant No.qiankehezhicheng-[2020]1Y025)。
文摘Phosphorus(Pi)plays a crucial role in the growth and development of plants.Membrane lipid regulation is one of the main mechanisms underlying plant adaptation to Pi deficiency.Previously,the high tolerance to low-Pi stress was justified in an elite line,MSDZ 109,which was obtained from Malus mandshurica.To better understand the mechanism underlying high adaptation to low-Pi stress,currently,lipidomic and transcriptomic analysis,as well as CRISPR/Cas9 and MmGDPD1-overexpressing methodologies were comprehensively integrated into a strategy for elucidating the high tolerance to low-Pi stress.Totally,770 differential metabolites were identified from the roots between the low-Pi and stress-free,belonging to 21 sub-classes of lipid compounds.Fatty acids(FA)constituted the predominant lipid component,accounting for approximately 50%-60%of the total lipids,and triglycerides(TAG)ranked the second,comprising around 12%of the total,consecutively followed by phosphatidylcholine(PC)and diacylglycerol(DAG)with approximately 10%and 8%of the total,respectively.The synchronous transcriptomic analysis revealed a significant up-regulation of genes related to glycerophospholipid and glycerolipid metabolism,specifically those(e.g.,MmGDPD1,MmDGDG1,MmMGDG1,MmSQDG,etc.)involved in phospholipid and galactosyl synthesis in response to low-Pi stress.GUS fusing reporter assay showed that MmGDPD1 promoter induced GUS gene expression and demonstrated initiation activity.Based on expression analysis,a dual-luciferase reporter assay,as well as yeast one-hybrid(Y1H)identification,MmPHR1 was justified to bind with the MmGDPD1 promoter and positively regulate plant tolerance to low-Pi stress.To further elucidate the role of MmGDPD1,CRISPR/Cas9 and MmGDPD1-overexpressing vectors were successfully introduced into apple(‘Royal Gala')calli.Interestingly,the MmGDPD1-KO line calli exhibited the remarkable decreases in the contents of phosphodiesterase(PDE),activity,as well as the contents of total Pi,and Pi in comparison with those of the wild type.Conversely,MmGDPD1-OE ones demonstrated the significant elevation in Pi accumulations,further justifying its potential role in Pi remobilization in apple.Therefore,MmGDPD1 substantially involves elevating low-Pi tolerance via promoting Pi release in M.mandshurica.
基金Open Access funding enabled and organized by Projekt DEALfinancially supported by H. Wilhelm Schaumann foundation。
文摘Background In contrast to protein-rich insect meal,the feed potential of insect fat is generally less explored and knowledge about the suitability of insect fat as a fat source specifically in broiler diets is still limited.In view of this,the present study aimed to comprehensively investigate the effect of partial(50%) and complete replacement of soybean oil with insect fat from Hermetia illucens(HI) larvae in broiler diets on performance,fat digestibility,cecal microbiome,liver transcriptome and liver and plasma lipidomes.Thus,100 male,1-day-old Cobb 500 broilers were randomly assigned to three groups and fed three different diets with either 0(group HI-0,n cens(HI) larvae fat for 35 d.= 30),2.5%(group HI-2.5,n %(HI-5.0,n = 35) or 5.0= 35) Hermetia illuResults Body weight gain,final body weight,feed intake,and feed:gain ratio during the whole period and apparent ileal digestibility coefficient for ether extract were not different between groups.Cecal microbial diversity did not differ between groups and taxonomic analysis revealed differences in the abundance of only four low-abundance bacterial taxa among groups;the abundances of phylum Actinobacteriota,class Coriobacteriia,order Coriobacteriales and family Eggerthellaceae were lower in group HI-5.0 compared to group HI-2.5(P < 0.05).Concentrations of total and individual short-chain fatty acids in the cecal digesta were not different between the three groups.Liver transcriptomics revealed a total of 55 and 25 transcripts to be differentially expressed between groups HI-5.0 vs.HI-0 and groups HI-2.5 vs.HI-0,respectively(P < 0.05).The concentrations of most lipid classes,with the exception of phosphatidylethanolamine,phosphatidylglycerol and lysophosphatidylcholine in the liver and cholesterylester and ceramide in plasma(P < 0.05),and of the sum of all lipid classes were not different between groups.Conclusions Partial and complete replacement of soybean oil with HI larvae fat in broiler diets had no effect on growth performance and only modest,but no adverse effects on the cecal microbiome and the metabolic health of broilers.This suggests that HI larvae fat can be used as an alternative fat source in broiler diets,thereby,making broiler production more sustainable.
基金the National Natural Science Foundation of China(81871043 and 82071494)the National Science and Technology Major Project of China(2018ZX09201017 and 2018ZX09201018)the 1.3.5 Project for Disciplines of Excellence,West China Hospital,Sichuan University(ZYGD18024).
文摘Drug-associated reward memories are conducive to intense craving and often trigger relapse.Simvastatin has been shown to regulate lipids that are involved in memory formation but its influence on other cognitive processes is elusive.Here,we used a mass spectrometry-based lipidomic method to evaluate the impact of simvastatin on the mouse brain in a cocaine-induced reinstatement paradigm.We found that simvastatin blocked the reinstatement of cocaine-induced conditioned place preference(CPP)without affecting CPP acquisition.Specifically,only simvastatin administered during extinction prevented cocaine-primed reinstatement.Global lipidome analysis showed that the nucleus accumbens was the region with the greatest degree of change caused by simvastatin.The metabolism of fatty-acids,phospholipids,and triacylglycerol was profoundly affected.Simvastatin reversed most of the effects on phospholipids induced by cocaine.The correlation matrix showed that cocaine and simvastatin significantly reshaped the lipid metabolic pathways in specific brain regions.Furthermore,simvastatin almost reversed all changes in the fatty acyl profile and unsaturation caused by cocaine.In summary,pre-extinction treatment with simvastatin facilitates cocaine extinction and prevents cocaine relapse with brain lipidome remodeling.
基金supported by the National Natural Science Foundation of China(31901577)the Fundamental Research Funds for the Central Universities,China(SWU-KT22035)the State Key Laboratory of Cotton Biology Open Fund,China(CB2021A32)。
文摘Calcium(Ca^(2+))plays an important role in determining plant growth and development because it maintains cell wall and membrane integrity.Therefore,understanding the role of Ca^(2+)in carbon and lipid metabolism could provide insights into the dynamic changes in cell membranes and cell walls during the rapid elongation of cotton fibers.In the present study,we found that the lack of Ca^(2+)promoted fiber elongation and rapid ovule expansion,but it also caused tissue browning in the ovule culture system.RNA-sequencing revealed that Ca^(2+)deficiency induced cells to be highly oxidized,and the expression of genes related to carbon metabolism and lipid metabolism was activated significantly.All gene members of nine key enzymes involved in glycolysis were up-regulated,and glucose was significantly reduced in Ca^(2+)deficiency-treated tissues.Ca^(2+)deficiency adjusted the flowing of glycolysis metabolic.However,low K^(+)recovered the expression levels of glycolysis genes and glucose content caused by Ca^(2+)deficiency.Electrospray ionizationtandem mass spectrometry technology was applied to uncover the dynamic profile of lipidome under Ca^(2+)and K^(+)interacted conditions.Ca^(2+)deficiency led to the decrease of fatty acid(FA),diacylglycerol(DAG),glycolipid and the significant increase of triacylglycerol(TAG),phospholipid phosphatidylethanolamine(PE),phosphatidylglycerol(PG),and PC(phosphatidylcholine).Low K^(+)restored the contents of FA,phospholipids,and glycolipids,effectively relieved the symptoms caused by Ca^(2+)deficiency,and recovered the development of fiber cells.This study revealed dynamic changes in transcript and metabolic levels and uncovered the signaling interaction of Ca^(2+)deficiency and low K^(+)in glycolysis and lipid metabolism during fiber development.
文摘The term lipidome is mentioned to the total amount of the lipids inside the biological cells.The lipid enters the human gastrointestinal tract through external source and internal source.The absorption pathway of lipids in the gastrointestinal tract has many ways;the 1st way,the lipid molecules are digested in the lumen before go through the enterocytes,digested products are re-esterified into complex lipid molecules.The 2nd way,the intracellular lipids are accumulated into lipoproteins(chylomicrons)which transport lipids throughout the whole body.The lipids are re-synthesis again inside the human body where the gastrointestinal lipids are:(1)Transferred into the endoplasmic reticulum;(2)Collected as lipoproteins such as chylomicrons;or(3)Stored as lipid droplets in the cytosol.The lipids play an important role in many stages of the viral replication cycle.The specific lipid change occurs during viral infection in advanced viral replication cycle.There are 47 lipids within 11 lipid classes were significantly disturbed after viral infection.The virus connects with blood-borne lipoproteins and apolipoprotein E to change viral infectivity.The viral interest is cholesterol-and lipid raft-dependent molecules.In conclusion,lipidome is important in gastrointestinal fat absorption and coronavirus disease 2019(COVID-19)infection so lipidome is basic in gut metabolism and in COVID-19 infection success.
基金supported by the National Research Foundation of Korea(NRF)grant funded by the Korean government(MSIT)(Grant Nos.:NRF-2018R1A5A2024425,NRF-2012M3A9C4048796,and NRF-2021R1I1A4A01057387)funded by the National Institutes of Health Office of Research Infrastructure Programs(Grant No.:P40 OD010440)supported by Plant Genomics and Breeding Institute at Seoul National University.
文摘Lipidomics coverage improvement is essential for functional lipid and pathway construction.A powerful approach to discovering organism lipidome is to combine various data acquisitions,such as full scan mass spectrometry(full MS),data-dependent acquisition(DDA),and data-independent acquisition(DIA).Caenorhabditis elegans(C.elegans)is a useful model for discovering toxic-induced metabolism,highthroughput drug screening,and a variety of human disease pathways.To determine the lipidome of C.elegans and investigate lipid disruption from the molecular level to the system biology level,we used integrative data acquisition.The methyl-tert-butyl ether method was used to extract L4 stage C.elegans after exposure to triclosan(TCS),perfluorooctanoic acid,and nanopolystyrene(nPS).Full MS,DDA,and DIA integrations were performed to comprehensively profile the C.elegans lipidome by Q-Exactive Plus MS.All annotated lipids were then analyzed using lipid ontology and pathway analysis.We annotated up to 940 lipids from 20 lipid classes involved in various functions and pathways.The biological investigations revealed that when C.elegans were exposed to nPS,lipid droplets were disrupted,whereas plasma membrane-functionalized lipids were likely to be changed in the TCS treatment group.The nPS treatment caused a significant disruption in lipid storage.Triacylglycerol,glycerophospholipid,and ether class lipids were those primarily hindered by toxicants.Finally,toxicant exposure frequently involved numerous lipid-related pathways,including the phosphoinositide 3-kinase/protein kinase B pathway.In conclusion,an integrative data acquisition strategy was used to characterize the C.elegans lipidome,providing valuable biological insights into hypothesis generation and validation.
文摘The tear film covers the anterior eye and the precise balance of its various constituting components is critical for maintaining ocular health.The composition of the tear film amphiphilic lipid sublayer,in particular,has largely remained a matter of contention.The limiting concentrations of lipid amphiphiles in tears have also posed considerable challenges to their detection and accurate quantitation.Using systematic and sensitive lipidomic approaches,we reported the most comprehensive human tear lipidome to date;and conferred novel insights to the compositional details of the existent tear film model,in particular the disputable amphiphilic lipid sublayer constituents,by demonstrating the presence of cholesteryl sulfate,O-acyl-ω-hydroxy fatty acids,and various sphingolipids and phospholipids in tears.Lipidomic analysis of human tear fluid from patients with various subtypes of dry eye syndrome(DES)revealed structure-specific lipid alterations in DES,which could potentially serve as unifying indicators of disease symptoms and signs.The meibomian glands constitute the predominant source of lipid supply to the human tear fluid.Meibomian gland dysfunction(MGD)is a leading cause of evaporative dry eye and ocular discomfort,characterized by an unstable tear film principally attributed to afflicted delivery of lipids to the ocular surface.We investigated the longitudinal tear lipid alterations associated with disease alleviation and symptom improvement in a cohort of MGD patients undergoing eyelid-warming treatment for 12 weeks.Our preliminary data indicated that excess ocular surface phospholipase activity detrimental to tear film stability could be alleviated by eyelid warming alone without application of steroids and identify tear OAHFAs as suitable markers to monitor treatment response in MGD.
文摘Sacoglossan sea slugs have attracted considerable scientific attention due to their capacity to retain functional macroalgal chloroplasts inside their cells.This endosymbiotic association is nutritionally relevant for these organisms and represents an interesting research issue for biotechnological applications.The Caribbean species Elysia crispata can integrate chloroplasts from different macroalgal species.The lipidome of chloroplasts includes lipid classes unique to these photosynthetic organelles.Specialized lipids,such as the glycolipids MGDG,DGDG,and SQDG,are essential for maintaining the integrity of both the thylakoid membranes and the overall chloroplast membrane structure.Additionally,lipids are a diverse group of biomolecules playing essential roles at nutritional and physiological levels.A combined approach using LC–HR-MS and MS/MS was employed to determine the polar lipid profile of the photosynthetic sea slug E.crispata from two habitats in the north-western tropical Atlantic(Sistema Arrecifal Veracruzano and Mahahual)and two different feeding conditions(fed and after 1 week of starvation).Significant differences were identified in the abundance of structural and signalling phospholipids(PC,PI,PG,PS,CL)suggesting different nutritional states between populations.The composition of glycolipids demonstrated a clear separation by habitat,but not by feeding conditions.The lower abundance of glycolipids in the Mahahual samples suggests a lower density of chloroplasts in their tissues compared to Veracruz individuals.These results corroborate that 1 week of starvation is insufficient to initiate the degradation of plastid membranes.This study confirms the advantages of using lipidomics as a tool to enhance our knowledge of the ecology of marine invertebrates.
基金supported by The Strategic Priority Research Program of the Chinese Academy of Sciences(XDB42030000)The National Key Research and Development Program of China(2022YFC2805400,2016YFC0304905)+1 种基金The National Natural Science Foundation of China(42330405)The National Natural Science Foundation of China(41876179).
文摘The hadal zone environment,characterized by extreme hydrostatic pressure,low temperatures,and limited food availability,presents substantial survival challenges for deep-sea fish species.In this study,we captured five deepsea fish species(Bathysaurus mollis,Coryphaenoides rudis,Ilyophis sp.,I.brunneus and Pseudoliparis swirei)from the Mariana Trench at depths ranging from 2027 to 7125 m,by employing China's“Exploration I and Exploration II”.By combining lipidomic and proteomic analyses,we aimed to explore the genetic basis of adaptive evolution to the hadal zone in fish.The results indicate several key findings:(1)P.swirei(Mariana hadal snailfish,MHS)may enhance energy storage and utilization during prolonged fasting periods by significantly increasing liver tissue levels of cholesterol ester(CE),ether-linked triacylglycerol(TG-O),coenzyme Q(CoQ),and ATPase content;(2)MHS could maintain membrane fluidity under high pressure by increasing the proportion of unsaturated fatty acids while reducing levels of cholesterol and phosphatidylethanolamine(PE)content.(3)The regulation of lipid types and ratios could increase the risk of lipid peroxidation.To counter oxidative stress,MHS likely elevates monounsaturated fatty acid content and enhances antioxidants such as transferrin and heat shock proteins.Overall,this study provides new insights into the adaptive mechanisms of MHS to deep-sea conditions through the lipidome and proteome analyses,thus broadening our understanding of its resilience in the hadal zone.
基金the Natural Science Foundation of China(31925037).
文摘Lipid metabolism is very important for meat quality in pigs.Accumulating evidence shows that gut microbiota can contribute to this physiological process.However,the gut microbiota that function in lipid metabolism and adipogenesis remains unclear.Here,we compared the characteristics of fat deposition and gut microbial community between Laiwu pigs and Duroc(LandraceYorkshire)(DLY)pigs.Fecal microbiota transplantation(FMT)was performed to determine the possible impact of gut microbiota on lipid metabolism in pigs.An integrated analysis of the gut microbiome and lipidome of the small intestine,plasma,and liver was conducted to investigate the effects of FMT on host lipid metabolism.The comparative analysis of the gut microbiome showed higher abundance of Bacteroidetes(P=0.0018)while lower abundance of Firmicutes(P=0.012)in Laiwu pigs,and the microbial composition can be transferred from Laiwu pigs into DLY pigs.Transmission electron microscope and Oil red-O staining were performed to analyze the effects of FMT on lipid deposition in liver,the main target organ for lipid metabolism.The results showed that FMT significantly increased the number of lipid droplets(P=0.0035)and lipid accumulation(P=0.0026)in liver.Furthermore,integrated multi-tissues lipidome analysis demonstrated that the fatty acyls and glycerophospholipids were significantly increased(P<0.01)in intestine and liver,while glycerolipids and fatty acyls were reduced(P<0.01)in plasma.In the small intestine,FMT increased(P<0.01)the relative abundance of polyketides and prenol lipids but reduced(P<0.01)the saccharolipids.Correlation analysis revealed the potential interactions between microbiota and lipid metabolites.Together,our results indicated that the gut microbiota may regulate the lipid metabolism and enhance the accumulation of lipid droplets in the liver of pigs.
基金supported by the Science and Technology Program of Tianjin in China(No.23ZYJDSS00030)the Public Applied Technology Research Project of Zhejiang Province(No.LGD22H090010)。
文摘Background:Sargentodoxae Caulis(SC)is the vine stem of Sargentodoxa Cuneata(Oliv.)Rehd.&E.H.Wilson in C.S.Sargent,and it in traditional Chinese medicine has been known for promoting blood circulation and removing blood stasis as recorded in the ancient book“Illustrated Classics of Materia Medica”.It has been used effectively to treat blood stasis too in modern clinical practice.However,the anti-hyperlipidemia effect of SC is not fully understood.This paper aims at exploring the use of SC stems to improve the balance of blood lipids in the body,and its new role in treating hyperlipidemia.Methods:The effects of SC extract on hyperlipidemia were explored by combining lipidomics and gut microbiota.Secondly,we explored the potential mechanism of SC in treating hyperlipidemia by pathway analysis.Results:The results showed that the stem extract of SC could restore the physiological and biochemical indices of hyperlipidemia in mice,as well as repair the morphological and structural damage to tissues.Compared to the Model group,the SC extract significantly reduced the liver index,epididymal fat index,and Lee’s index.It also significantly decreased serum levels of total cholesterol,triglycerides,low-density lipoprotein cholesterol,peroxisome proliferator-activated receptor gamma(PPAR-γ),D-lactate,and free fatty acids,while significantly increasing the relative content of peroxisome proliferator-activated receptor alpha(PPAR-α).These changes were statistically significant.Non-targeted lipidomics,based on LC-MS,were utilized to investigate the lipid metabolism characteristics in serum,liver,and epididymal fat of the subjects.It was observed that,compared to the blank group,the Model group exhibited significant changes primarily in glycerol lipids and glycerophospholipids.The treatment group also displayed alterations in these lipids.A total of 38,81,and 27 differential lipids were identified in serum,liver,and epididymal fat samples,respectively.Among these,14 common differential lipids were found in both serum and liver samples,and their KEGG enrichment pathways were largely consistent.Among them,the sphingolipid signaling pathway and the glycerophospholipid metabolic pathway were identified as key metabolic pathways that were regulated.Our gut microbiota analysis revealed that SC diminishes the abundance of Actinobacteria by altering the cecal flora in mice.Conclusion:This alteration leads to the downregulation of genes involved in triglyceride metabolism,which in turn changes lipid processing and reduces triglyceride levels.Consequently,SC effectively combats hyperlipidemia.Notably,SC impacts key metabolic pathways,including the sphingolipid signaling and glycerophospholipid metabolism.These findings underscore SC’s therapeutic potential,positioning it as a promising alternative for reducing the health risks associated with hyperlipidemia.
基金supported by the National Key Research and Development Program of China(No.2018YFE0207300)Beijing Natural Science Foundation(No.M23008)+1 种基金the National High Level Hospital Clinical Research Funding(No.2022-PUMCH-B-124)the National High Level Hospital Clinical Research Funding(No.2022-PUMCH-A-057)。
文摘Varicocele(VC)is a common cause of male infertility,yet there is a lack of molecular information for VC-associated male infertility.This study investigated alterations in the seminal plasma metabolomic and lipidomic profiles of infertile male VC patients.Twenty infertile males with VC and twenty-three age-matched healthy controls(HCs)were recruited from Peking Union Medical College Hospital(Beijing,China)between October 2019 and April 2021.Untargeted metabolite and lipid profiles from seminal plasma were analyzed using mass spectrometry.Four hundred and seventy-six metabolites and seventeen lipids were significantly different in infertile male VC patients compared to HCs.The top enriched pathways among these significantly different metabolites are protein digestion and absorption,aminoacyl-transfer RNA(tRNA)biosynthesis,and biosynthesis of amino acids.Different key lipid species,including triglyceride(TG),diacylglycerol(DG),ceramides(Cer),and phosphatidylserine(PS),varied betweenVC and HC groups.The distinct metabolites and lipids were moderately correlated.DL-3-phenyllactic acid is a potential diagnostic biomarker for VC-related male infertility(area under the curve[AUC]=0.893),positively correlating with sperm count,concentration,and motility.Furthermore,DL-3-phenyllactic acid is the only metabolite shared by all four comparisons(VC vs HC,VC-induced oligoasthenospermia[OAS]vs VC-induced asthenospermia[AS],OAS vs HC,and AS vs HC).DL-3-phenyllactic acid significantly decreased in OAS than AS.Metabolite-targeting gene analysis revealed carbonic anhydrase 9(CA9)might be the strongest candidate associated with the onset and severity of VC.The seminal plasma metabolite and lipid profiles of infertile males with VC differ significantly from those of HCs.DL-3-phenyllactic acid could be a promising biomarker.
基金supported by the National Natural Science Foundation of China(No.82173947).
文摘Astragali Radix(AR), a traditional Chinese medicine(TCM), has demonstrated therapeutic efficacy against various diseases, including cardiovascular conditions, over centuries of use.While doxorubicin serves as an effective chemotherapeutic agent against multiple cancers, its clinical application remains constrained by significant cardiotoxicity. Research has indicated that AR exhibits protective properties against doxorubicin-induced cardiomyopathy(DIC);however, the specific bioactive components and underlying mechanisms responsible for this therapeutic effect remain incompletely understood. This investigation seeks to identify the protective bioactive components in AR against DIC and elucidate their mechanisms of action.Through network medicine analysis, astragaloside Ⅳ(AsⅣ) and formononetin(FMT) were identified as potential cardioprotective agents from 129 AR components. In vitro experiments using H9c2 rat cardiomyocytes revealed that the AsⅣ-FMT combination(AFC) effectively reduced doxorubicin-induced cell death in a dose-dependent manner, with optimal efficacy at a 1∶2 ratio. In vivo, AFC enhanced survival rates and improved cardiac function in both acute and chronic DIC mouse models. Additionally, AFC demonstrated cardiac protection while maintaining doxorubicin's anti-cancer efficacy in a breast cancer mouse model. Lipidomic and metabolomics analyses revealed that AFC normalized doxorubicin-induced lipid profile alterations, particularly by reducing fatty acid accumulation. Gene knockdown studies and inhibitor experiments in H9c2 cells demonstrated that AsⅣ and FMT upregulated peroxisome proliferator activated receptor γ coactivator 1α(PGC-1α) and PPARα, respectively, two key proteins involved in fatty acid metabolism. This research establishes AFC as a promising therapeutic approach for DIC, highlighting the significance of multi-target therapies derived from natural herbals in contemporary medicine.
基金supported by grants from NHMRC(Grant No.1125514 and 2029334 to JRM,and 1120129 to JRM and CEH)National Heart Foundation of Australia(Vanguard-105720)+6 种基金the Victorian Government’s Operational Infrastructure Support Programsupported by a joint Baker Heart and Diabetes Institute-La Trobe University doctoral scholarshipsupported by Future Leader Fellowships from the National Heart Foundation of Australia(Grant No.102536 to EJH,102539 to KLW,and 102206 to ALG)supported by an Alice Baker and Eleanor Shaw Fellowship(The Baker Foundation,Australia)supported by a NHMRC Senior Research(Grant No.1078985)Baker Fellowship(The Baker Foundation,Australia)Cardiovascular Research Capacity Program-Research Leadership GrantsCardiovascular Research Capacity Program-Research Leadership Grants(NSW Health)。
文摘Background:Elucidating mechanisms underlying atrial myopathy,which predisposes individuals to atrial fibrillation(AF),will be critical for preventing/treating AF.In a serendipitous discovery,we identified atrial enlargement,fibrosis,and thrombi in mice with reduced phosphoinositide 3-kinase(PI3K)in cardiomyocytes.PI3K(p110a)is elevated in the heart with exercise and is critical for exercise-induced ventricular enlargement and protection,but the role in the atria was unknown.Physical inactivity and extreme endurance exercise can increase AF risk.Therefore,our objective was to investigate whether too little and/or too much PI3K alone induces cardiac pathology.Methods:New cardiomyocyte-specific transgenic mice with increased or decreased PI3K(p110a)activity were generated.Multi-omics was conducted in mouse atrial tissue,and lipidomics in human plasma.Results:Elevated PI3K led to an increase in heart size with preserved/enhanced function.Reduced PI3K led to atrial dysfunction,fibrosis,arrhythmia,increased susceptibility to atrial enlargement and thrombi,and dysregulation of monosialodihexosylganglioside(GM3),a lipid that regulates insulin-like growth factor-1(IGF1)-PI3K signaling.Proteomic profiling identified distinct signatures and signaling networks acrossatria with varying degrees of dysfunction,enlargement,and thrombi,including commonalities with the human AF proteome.PI3K-related lipids were dysregulated in plasma from athletes with AF.Conclusion:PI3K(p110a)is a critical regulator of atrial biology and function in mice.This work provides a proteomic resource of candidates for further validation as potential new drug targets and biomarkers for atrial myopathy.Further investigation of PI3K-related lipids as markers for identifying individuals at risk of AF is warranted.Dysregulation of PI3K may contribute to the association between increased cardiac risk with physical inactivity and extreme endurance exercise.
基金National Natural Science Foundation of China(81774383)Major Project of Philosophy and Social Science Research in Colleges and Universities of Jiangsu Province (2020SJA0335)Graduate Research and Innovation Projects of Jiangsu Province (SJCX23_0735)。
文摘Objective To reveal the therapeutic effects of moxibustion in collagen-induced arthritis(CIA)rat models using the combined analysis of plasma and synovial membrane lipidomic profil-ing and to enhance the understanding of how moxibustion affects lipid metabolism in rheumatoid arthritis(RA).Methods A total of 32 male Sprague-Dawley(SD)rats were randomly assigned to four groups:control,moxibustion control(MC),model,and moxibustion model(MM)groups,with 8 rats in each group.CIA was induced in SD rats by two immunizations.The paw volume was mea-sured before the induction of CIA.Following induction,after assessing paw volume and arthritis index(AI)scores,the MC and MM groups received treatment at bilateral Shenshu(BL23)and Zusanli(ST36)acupoints for 10 min per acupoint.The intervention included three treatment courses,each spanning 6 d and followed by a 1-d interval.Paw volume and AI scores were assessed after each treatment course.After the completion of the three treatment courses,serum,plasma,synovial tissue,and ankle joint samples were collected.Enzyme-linked immunosorbent assay(ELISA)was employed to quantify the levels of interleukin(IL)-6 and tumor necrosis factor(TNF)-αin serum.Hematoxylin and eosin(HE)staining was per-formed for histopathological examination of the ankle joint tissues.Meanwhile,ultra-high-performance liquid chromatography coupled with Q-Exactive Orbitrap mass spectrometry(UHPLC-Q-Exactive Orbitrap MS)was utilized to analyze the plasma and synovial tissue sam-ples.In addition,multivariate statistical analysis was performed to identify differential lipid metabolites,and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analysis was applied to explore metabolic pathways modulated by moxibustion therapy.Results No significant difference in hind paw volume and AI scores was observed among the groups(P>0.05).After CIA induction,model group showed increased hind paw volume and AI scores compared with control group(P<0.05),which were significantly reduced after mox-ibustion treatment in MM group compared with model group(P<0.05).The levels of IL-6 and TNF-αwere significantly higher in model and MM groups compared with control group(P<0.05),but were lower in MM group than those in model group(P<0.05).Histopathologi-cal analysis showed improved cartilage and reduced inflammation in MM group.A total of 33 differential lipid metabolites in the plasma and 24 in the synovial membranes of CIA rat mod-els were identified when compared with control group.Among these lipid metabolites,31 in the plasma and all 24 in the synovial membranes were regulated by moxibustion treatment.Pathological analysis revealed upregulation of diacylglycerol(DG)and fatty acid(FA)levels,alongside downregulation of lysophosphatidylcholine(LPC),phosphatidylcholine(PC),and phosphatidylethanolamine(PE).Under physiological conditions,the treatment specifically reduced LPC and PC levels.Pathway enrichment analysis revealed that moxibustion predom-inantly affectedα-linolenic acid,glycerophospholipid,and sphingolipid metabolism under pathological conditions.Under physiological conditions,the regulation was centered aroundα-linolenic acid and glycerophospholipid metabolism.Conclusion The RA rat models exhibited significant lipid metabolic disturbances.Moxibus-tion alleviated paw swelling,reduced AI scores,modulated inflammatory cytokine levels,and partially corrected the altered levels of multiple lipid metabolites.The potential metabolic pathways implicated in the regulation of lipid metabolism under both physiological and pathological conditions includeα-linolenic acid,glycerophospholipid,and sphingolipid metabolism.
基金supported by the National Natural Science Foundation of China(32372367)the earmarked fund for CARS(CARS-47)+1 种基金Natural Science Foundation of Hainan Provine(323CXTD391)the Special Scientific Research Funds for Central Non-profit Institutes and the Chinese Academy of Fishery Sciences(2020TD69)。
文摘Inoculated fermentation enables rapid fermentation of aquatic products.No studies have been conducted on the lipid profiles of inoculated fermented golden pompano(Trachinotus ovatus).In this study,a lipase-producing Bacillus subtilis with salt tolerance was screened from traditionally fermented golden pompano(TF)and used as a starter culture.Whole-genome sequencing analysis revealed it carries 4 clustered regularly interspaced short vpalindromic repeats structures and 2 genes encoding triacylglycerol lipase.Untargeted lipidomics identified lipid molecules(833)in 6 major classes from B.subtilis SCSMX-2 fermented golden pompano(IF).A total of 28 lipid molecules were upregulated in IF,including phosphatidylcholines(PCs),triacylglycerols(TAGs),and lysophosphatidylcholine.B.subtilis supplementation enhanced the production of polyenyl PCs and mediumand long-chain TAGs.The IF rich in linoleic,docosahexaenoic acids(DHA),and eicosapentaenoic acid were primarily distributed in the sn-2 position of DHA,PC and phosphatidylethanolamine.This research revealed the lipid profiles of IF,providing theoretical basis for the application of B.subtilis in the fermented fish industry.
基金supported by the Science and Technology Department of Jiangxi Province(20212AEI91010)National Natural Science Foundation of China(31772067)+1 种基金Jiangxi Agriculture Research System(JXARS-14)Research Project of State Key Laboratory of Food Science and Technology(SKFL-ZZB-2)。
文摘Royal jelly(RJ)is rich in various nutrients with multiple health-promoting properties.This study aims to evaluate whether RJ can modulate related metabolite in the natural aging mice.Male C57BL/6J mice drank RJ solution daily for 9 months.Determination of serum lipids and pathological analysis exhibited that triglycerides,serum cholesterol,and low-density lipoprotein cholesterol were decreased by 31.15%,9.96%,and 22.58%,respectively,the morphology of brain nerve cells was also effectively recovered after RJ intervention.Lipidomic analysis showed that RJ could improve the levels of different kinds of lipids in aging mice brain,especially by increasing the content of antioxidant ether ester,and that the ratio of monounsaturated fatty acid to polyunsaturated fatty acid was up by 23.46%,which could alleviate oxidative stress.Moreover,the metabolism of glycerol phospholipids,glycerols,and fatty acids in aging mice could be regulated by RJ.RJ intervention can effectively improve lipid metabolism disorders caused by aging.
基金supported by the National Natural Science Foundation of China (Nos. 81903384and 82173596)Suzhou Municipal Science and Technology Bureau (No. SKY2023041 and SKY2023180)+3 种基金the Inner Mongolia Autonomous Region Science and Technology Program (Nos.2022YFSH0054 and 2023GLLH0387)the Clinical Research Center of Neurological Disease of The Second Affiliated Hospital of Soochow University(ND2023B06)the Shaanxi Provincial Natural Science Basic Research Program (2025JC-YBMS-1020)Undergraduate Extracurricular Academic Research Funding of Soochow University (KY2023442B)
文摘Objective Lipid oxidation is involved in the pathogenesis of atherosclerosis and may be contribute to the development of Ischemic stroke(IS).However,the lipid profiles associated with IS have been poorly studied.We conducted a pilot study to identify potential IS-related lipid molecules and pathways using lipidomic profiling.Methods Serum lipidomic profiling was performed using LC-MS in 20 patients with IS and 20 age-and sex-matched healthy controls.Univariate and multivariate analyses were simultaneously performed to identify the differential lipids.Multiple testing was controlled for using a false discovery rate(FDR)approach.Enrichment analysis was performed using MetaboAnalyst software.Results Based on the 294 lipids assayed,principal component analysis(PCA)and orthogonal partial least squares discriminant analysis(OPLS-DA)models were used to distinguish patients with IS from healthy controls.Fifty-six differential lipids were identified with an FDR-adjusted P less than 0.05 and variable influences in projection(VIP)greater than 1.0.These lipids were significantly enriched in glycerophospholipid metabolism(FDR-adjusted P=0.009,impact score=0.216).Conclusions Serum lipid profiles differed significantly between patients with IS and healthy controls.Thus,glycerophospholipid metabolism may be involved in the development of IS.These results provide initial evidence that lipid molecules and their related metabolites may serve as new biomarkers and potential therapeutic targets for IS.
基金supported by a project grant awarded to Hui Chen and Brian G.Oliver by the Australian National Health&Medical Research Council(No.APP1158186)supported by scholarships from the Chinese Scholarship Councilsupported by scholarships from the Australian Government Research Training Program。
文摘There is no safe level of exposure to air pollution,including particulate matter smaller than2.5μm(PM_(2.5)),to human health.Whilst it is well known that exposure to heavily polluted air is associated with several liver disorders,it is unclear how long-term exposure to lowlevel traffic-derived PM_(2.5)affects liver health.BALB/c mice(5 weeks,male)were exposed to traffic-derived PM_(2.5)(10μg/mouse/day,intranasally)daily for 4,8 and 12 weeks.Markers of inflammation and fibrosis were measured at each time point.Changes in liver proteome and lipid profiles were measured using proteomics and lipidomics at 12 weeks.Low-dose PM_(2.5)exposure increased macrophage infiltration,pro-inflammatory cytokine production,and increased collagen deposition at 12 weeks.Despite liver lipid metabolism being increased,the abundance of triglycerides,precursor diacylglycerols,and ceramide was also significantly increased by PM_(2.5)exposure,whereas glycogen content was reduced.Proteomics analysis revealed 64 proteins to be significantly changed in PM_(2.5)-exposed mice,and KEGG pathway enrichment analysis indicated their involvement in lipid metabolism,alcohol-related liver disease,neutrophil extracellular trap formation,and transcriptional dysregulation related to cancer.In conclusion,prolonged exposure to low-dose traffic-derived PM_(2.5)promotes pathological changes in the liver,suggestive of an increased risk of metabolic dysfunctionassociated fatty liver disease.Future studies can enable the identification of the signalling pathways underlying low-dose PM_(2.5)-induced lipid accumulation in the liver.
基金graciously funded by the Central Government Guidance Fund for Supporting the Local Science and Technology Development(No.XZ202101YD0002C).
文摘Background:Developmental dysplasia of the hip(DDH)is a prevalent pediatric condition with a multifactorial etiology.Its incidence varies geographically,with notably higher rates observed on the Xizang plateau.This study was performed to evaluate the lipidomics signatures associated with DDH by analyzing plasma samples.Methods:Fifty infants were recruited,including 25 diagnosed with DDH and 25 age-matched healthy controls.In addition to plasma samples,comprehensive laboratory test results and medical records were collected for each participant.An untargeted lipidomics profiling approach was employed to identify distinguishing metabolic signatures.Results:Lipidomics profiles differed significantly between patients with DDH and healthy controls.Several differential metabolites were identified,including triacylglycerol(TAG)(17:0/18:1/20:1),TAG(17:0/17:0/17:0),phosphatidylethanolamine(PE)(10:0/26:4),TAG(17:0/18:0/18:0),TAG(16:0/17:0/22:1),TAG(16:0/18:0/22:0),TAG(17:0/19:0/19:0),TAG(13:0/20:0/20:0),TAG(18:0/18:0/22:0),and TAG(16:0/20:0/20:0).The primary lipid species showing differences were TAGs and PE.Conclusions:Distinct shifts in lipidomics profiles were observed in infants with DDH.To the best of our knowledge,this study is the first to explore lipidomics signatures in patients with DDH.The combined assessment of TAG(17:0/18:1/20:1)and TAG(17:0/17:0/17:0)may serve as a potential diagnostic tool for DDH.
