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
Adenomyosis is a common gynecological disease characterized by the invasion of endometrial glands and stroma into the myometrium of uterus,the pathological mechanism of which remains unclear yet.Disturbed lipid metabo...Adenomyosis is a common gynecological disease characterized by the invasion of endometrial glands and stroma into the myometrium of uterus,the pathological mechanism of which remains unclear yet.Disturbed lipid metabolism extensively affects abnormal cell proliferation and invasion in various diseases.However,the lipidome signature of human myometrium,which could be crucial in the development of adenomyosis,remains unknown.In this study,we generated the first lipidome profiling of human myometrium using a high-coverage and quantitative lipidomics approach based on ultraperformance liquid chromatography(UPLC)coupled with triple quadrupole(QqQ)-mass spectrometry(MS).A total of 317 lipid species were successfully quantified in the myometrial tissues from women with(n=38)or without(n=65)adenomyosis who underwent hysterectomy at Peking Union Medical College Hospital(Bejing,China).Up to 83 lipid species showed significant alternations in content between the two groups.These lipid aberrations involved multiple metabolic pathways,and emphasized inflammation,cell migration,and immune dysregulation upon adenomyosis.Moreover,receiver operating characteristic(ROC)curve analysis found that the combination of five lipid species could accurately distinguished the myometrial samples from women with and without adenomyosis with an area under the curve(AUC)of 0.906.Desorption electrospray ionization MS imaging(MSI)further underscored the heterogeneous distributions of these lipid markers in the adenomyosis lesion and adjacent myometrial tissue.Collectively,these results extremely improved our understanding on the molecular basis of adenomyosis,and could shed light on developing potential biomarkers and new therapeutic directions for adenomyosis.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
Bifidobacterium animalis subsp.lactis 420(B420),serving as a probiotic helping in metabolic health,has been extensively studied.Since the lipids produced by Bifidobacterium animalis subsp.lactis 420(B420)exhibit varia...Bifidobacterium animalis subsp.lactis 420(B420),serving as a probiotic helping in metabolic health,has been extensively studied.Since the lipids produced by Bifidobacterium animalis subsp.lactis 420(B420)exhibit variable bioactivities,understanding lipid profile alterations across different cultivation phases could offer valuable insights for developing targeted production strategies that enhance both the yield and bioactivity of specific lipid constituents.However,studies elucidating these lipid profile changes throughout various cultivation phases are limited,yet such research is essential for facilitating effective production strategies aimed at optimizing the yield and bioactivity of desired lipid components.Linoleic acid supplementation has been reported to enhance the production of unsaturated fatty acids in Bifidobacterium animalis subsp.lactis 420(B420).This study aimed to reveal the lipidomics of B420 and its profile change during the cultivation.Using ultra-performance liquid chromatography/nano-electrospray ionization-tandem mass spectrometry,the investigation revealed a significantly diverse composition and relative intensity of lipids across different cultivation stages.A total of 862 lipids,categorized into 23 distinct lipid classes,were identified in B420.Among these,683 unsaturated lipids comprised nearly 70%of the total lipid pool.Following linoleic acid supplementation,the total number of identified lipid compounds increased to 891,with unsaturated lipids rising to 701,which included 509 polyunsaturated lipids.Additionally,the relative content of unsaturated lipids at each growth phase demonstrated a significant increase,peaking at 75.69%during the late stationary phase,which is 8.89%higher than observed in the absence of linoleic acid supplementation.The intensity of unsaturated fatty acyls increased to 13.55 times.Notably,linoleic acid induced the production of unsaturated lipids characterized by varying numbers and distributions of double bonds.For the first time,this study enhances our understanding of the lipid profile changes in B420 and reveals the compositional and quantitative variations of unsaturated lipids resulting from linoleic acid supplementation during cultivation.Our research provided a new understanding of the probiotic effects of B420 from a lipidomic perspective and elucidate the mechanisms underlying linoleic acid supplementation during cultivation.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
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
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
Although human milk fat substitute(HMFS)has been wildly applied in infant formula(IF),there are still some differences in fat composition between human milk and IF,which is extremely attributed to the phospholipid com...Although human milk fat substitute(HMFS)has been wildly applied in infant formula(IF),there are still some differences in fat composition between human milk and IF,which is extremely attributed to the phospholipid composition.We therefore designed a human milk phospholipid substitute(HMPS),and investigated its nutritional outcomes on brain development using C57BL/6J mice.Results showed that HMPS improved mice's cognitive behavior and dendritic development compared to soybean phospholipids and nophospholipid diets.Based on the lipidomics,we revealed that these beneficial outcomes were potentially associated with the increased biosynthesis of N-acylethanolamines,phosphatidylethanolamine(PE),and ether PE,and the decreased metabolism of diacylglycerol and hexosylceramide in brain.It was further found in Kyoto Encyclopedia of Genes and Genomes analysis that glycerophospholipid metabolic pathway participated in the improvement of HMPS on mice's neurodevelopment.In conclusion,this study demonstrated that HMPS improves mice's neurodevelopment,and the glycerophospholipid metabolic pathway plays a major role in this beneficial result,and provided evidence for future application of HMPS in commercial IF.展开更多
Alzheimer’s disease is the most common cause of dementia.Although increasing evidence suggests that disruptions in lipid metabolism are closely associated with the disease,the overall profile of lipid and sterol chan...Alzheimer’s disease is the most common cause of dementia.Although increasing evidence suggests that disruptions in lipid metabolism are closely associated with the disease,the overall profile of lipid and sterol changes that occur in the brain during Alzheimer’s disease remains unclear.In this study,we compared brain tissues extracted from 32-week-old male wild-type mice and 5×FAD transgenic Alzheimer’s disease model mice,which carry mutations in the amyloid precursor protein(APP)and presenilin 1(PS1)genes.Using untargeted lipidomics and sterolomics techniques,we investigated the metabolic profiles of lipids,with a focus on sterols specifically,in three brain regions:cerebellum,hippocampus,and olfactory bulb.Our results revealed significant alterations in various lipids,particularly in the hippocampus and olfactory bulb,suggesting changes in energy levels in these regions.Further pathway analysis indicated notable disruptions in key metabolic processes,particularly those related to fatty acids and cell membrane components.Additionally,we observed decreased expression of 15 genes involved in lipid and sterol regulation.Collectively,these findings provide new insights into how imbalances in lipid and sterol metabolism may contribute to the progression of Alzheimer’s disease,highlighting potential metabolic pathways involved in the development of this debilitating disease.展开更多
Lipoprotein,especially high-density lipoprotein(HDL),particles are composed of multiple heterogeneous subgroups containing various proteins and lipids.The molecular distribution among these subgroups is closely relate...Lipoprotein,especially high-density lipoprotein(HDL),particles are composed of multiple heterogeneous subgroups containing various proteins and lipids.The molecular distribution among these subgroups is closely related to cardiovascular disease(CVD).Here,we established high-resolution proteomics and lipidomics(HiPL)methods to depict the molecular profiles across lipoprotein(Lipo-HiPL)and HDL(HDL-HiPL)subgroups by optimizing the resolution of anion-exchange chromatography and comprehensive quantification of proteins and lipids on the omics level.Furthermore,based on the Pearson correlation coefficient analysis of molecular profiles across high-resolution subgroups,we achieved the relationship of proteome–lipidome connectivity(PLC)for lipoprotein and HDL particles.By application of these methods to high-fat,high-cholesterol diet-fed rabbits and acute coronary syndrome(ACS)patients,we uncovered the delicate dynamics of the molecular profile and reconstruction of lipoprotein and HDL particles.Of note,the PLC features revealed by the HDL-HiPL method discriminated ACS from healthy individuals better than direct proteome and lipidome quantification or PLC features revealed by the Lipo-HiPL method,suggesting their potential in ACS diagnosis.Together,we established HiPL methods to trace the dynamics of the molecular profile and PLC of lipoprotein and even HDL during the development of CVD.展开更多
Lipids,once thought to be mainly for energy-storage and structural purpose,have now gained immense recognition as a class of critical metabolites with versatile functions.The diversity and complexity of the cellular l...Lipids,once thought to be mainly for energy-storage and structural purpose,have now gained immense recognition as a class of critical metabolites with versatile functions.The diversity and complexity of the cellular lipids are the main challenge for the comprehensive analysis of a lipidome.Lipidomics,which aims at mapping all of the lipids in a cell,is expanded rapidly in recent years,mainly attributed to recent advances in mass spectrometry(MS).MS-based lipidomic approaches developed recently allow the quick profiling of hundreds of lipids in a crude lipid extract.With the aid of latest computational tools/software(chemometrics),aberrant lipid metabolites or important signaling lipid(s)could be easily identified using unbiased lipid profiling approaches.Further tandem MS(MS/MS)-based lipidomic approaches,known as targeted approaches and able to convey structural information,hold the promise for highthroughput lipidome analysis.In this review,I discussed the basic strategy for systems level analysis of lipidome in biomedical study.展开更多
The SH-SY5Y,neuroblastoma cell line,is a common in vitro model used to study physiological neuronal function and the neuronal response to different stimuli,including exposure to toxic chemicals.These cells can be diff...The SH-SY5Y,neuroblastoma cell line,is a common in vitro model used to study physiological neuronal function and the neuronal response to different stimuli,including exposure to toxic chemicals.These cells can be differentiated to neuron-like cells by administration of various reagents,including retinoic acid or phorbol12-myristate-13-acetate.Despite their common use,there is an incomplete understanding of the molecular changes that occur during differentiation.Therefore,there is a critical need to fully understand the molecular changes that occur during differentiation to properly study neurotoxicity in response to various environmental exposures.Previous studies have investigated the proteome and transcriptome during differentiation;however,the regulation of the cellular lipidome in this process is unexplored.In this work,we conducted liquid chromatography−mass spectrometry(LC−MS)-based untargeted lipidomics in undifferentiated and differentiated SH-SY5Y cells,induced by retinoic acid.We show that there are global differences between the cellular lipidomes of undifferentiated and differentiated cells.Out of thousands of features detected in positive and negative electrospray ionization modes,44 species were identified that showed significant differences(p-value≤0.05,fold change≥2)in differentiated cells.Identification of these features combined with targeted lipidomics highlighted the accumulation of phospholipids,sterols,and sphingolipids during differentiation while triacylglycerols were depleted.These results provide important insights into lipid-related changes that occur during cellular differentiation of SH-5YSY cells and emphasize the need for the detailed characterization of biochemical differences that occur during differentiation while using this in vitro model for assessing ecological impacts of environmental pollutants.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
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supported by the National High Level Hospital Clinical Research Funding,China(Grant Nos.:2022-PUMCH-A-204 and 2022-PUMCH-C-031)the National Natural Science Foundation of China(Grant No.:82274336).
文摘Adenomyosis is a common gynecological disease characterized by the invasion of endometrial glands and stroma into the myometrium of uterus,the pathological mechanism of which remains unclear yet.Disturbed lipid metabolism extensively affects abnormal cell proliferation and invasion in various diseases.However,the lipidome signature of human myometrium,which could be crucial in the development of adenomyosis,remains unknown.In this study,we generated the first lipidome profiling of human myometrium using a high-coverage and quantitative lipidomics approach based on ultraperformance liquid chromatography(UPLC)coupled with triple quadrupole(QqQ)-mass spectrometry(MS).A total of 317 lipid species were successfully quantified in the myometrial tissues from women with(n=38)or without(n=65)adenomyosis who underwent hysterectomy at Peking Union Medical College Hospital(Bejing,China).Up to 83 lipid species showed significant alternations in content between the two groups.These lipid aberrations involved multiple metabolic pathways,and emphasized inflammation,cell migration,and immune dysregulation upon adenomyosis.Moreover,receiver operating characteristic(ROC)curve analysis found that the combination of five lipid species could accurately distinguished the myometrial samples from women with and without adenomyosis with an area under the curve(AUC)of 0.906.Desorption electrospray ionization MS imaging(MSI)further underscored the heterogeneous distributions of these lipid markers in the adenomyosis lesion and adjacent myometrial tissue.Collectively,these results extremely improved our understanding on the molecular basis of adenomyosis,and could shed light on developing potential biomarkers and new therapeutic directions for adenomyosis.
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.
基金supported by the National Key Research and Development Program of China(2023YFE0104400).
文摘Bifidobacterium animalis subsp.lactis 420(B420),serving as a probiotic helping in metabolic health,has been extensively studied.Since the lipids produced by Bifidobacterium animalis subsp.lactis 420(B420)exhibit variable bioactivities,understanding lipid profile alterations across different cultivation phases could offer valuable insights for developing targeted production strategies that enhance both the yield and bioactivity of specific lipid constituents.However,studies elucidating these lipid profile changes throughout various cultivation phases are limited,yet such research is essential for facilitating effective production strategies aimed at optimizing the yield and bioactivity of desired lipid components.Linoleic acid supplementation has been reported to enhance the production of unsaturated fatty acids in Bifidobacterium animalis subsp.lactis 420(B420).This study aimed to reveal the lipidomics of B420 and its profile change during the cultivation.Using ultra-performance liquid chromatography/nano-electrospray ionization-tandem mass spectrometry,the investigation revealed a significantly diverse composition and relative intensity of lipids across different cultivation stages.A total of 862 lipids,categorized into 23 distinct lipid classes,were identified in B420.Among these,683 unsaturated lipids comprised nearly 70%of the total lipid pool.Following linoleic acid supplementation,the total number of identified lipid compounds increased to 891,with unsaturated lipids rising to 701,which included 509 polyunsaturated lipids.Additionally,the relative content of unsaturated lipids at each growth phase demonstrated a significant increase,peaking at 75.69%during the late stationary phase,which is 8.89%higher than observed in the absence of linoleic acid supplementation.The intensity of unsaturated fatty acyls increased to 13.55 times.Notably,linoleic acid induced the production of unsaturated lipids characterized by varying numbers and distributions of double bonds.For the first time,this study enhances our understanding of the lipid profile changes in B420 and reveals the compositional and quantitative variations of unsaturated lipids resulting from linoleic acid supplementation during cultivation.Our research provided a new understanding of the probiotic effects of B420 from a lipidomic perspective and elucidate the mechanisms underlying linoleic acid supplementation during cultivation.
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 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supported by Huhhot Science&Technology Plan(2021-National Center of Technology innovation for Dairy-4)Innovation Consortium Project(2023RC Consortium-7)+3 种基金National Key Research and Development Program(2023YFF1104502)Ganpo Juncai supports the plan(20232BCJ22046)Nanchang University Jiangxi Financial Science and Technology Special Project(ZBG20230418011)Free Exploration Project of State Key Laboratory(SKLF-ZZB-202317).
文摘Although human milk fat substitute(HMFS)has been wildly applied in infant formula(IF),there are still some differences in fat composition between human milk and IF,which is extremely attributed to the phospholipid composition.We therefore designed a human milk phospholipid substitute(HMPS),and investigated its nutritional outcomes on brain development using C57BL/6J mice.Results showed that HMPS improved mice's cognitive behavior and dendritic development compared to soybean phospholipids and nophospholipid diets.Based on the lipidomics,we revealed that these beneficial outcomes were potentially associated with the increased biosynthesis of N-acylethanolamines,phosphatidylethanolamine(PE),and ether PE,and the decreased metabolism of diacylglycerol and hexosylceramide in brain.It was further found in Kyoto Encyclopedia of Genes and Genomes analysis that glycerophospholipid metabolic pathway participated in the improvement of HMPS on mice's neurodevelopment.In conclusion,this study demonstrated that HMPS improves mice's neurodevelopment,and the glycerophospholipid metabolic pathway plays a major role in this beneficial result,and provided evidence for future application of HMPS in commercial IF.
基金supported by the National Natural Science Foundation of China,Nos.82200784,32271311Qizhen Foundation,No.226‐2023‐00008(all to LH).
文摘Alzheimer’s disease is the most common cause of dementia.Although increasing evidence suggests that disruptions in lipid metabolism are closely associated with the disease,the overall profile of lipid and sterol changes that occur in the brain during Alzheimer’s disease remains unclear.In this study,we compared brain tissues extracted from 32-week-old male wild-type mice and 5×FAD transgenic Alzheimer’s disease model mice,which carry mutations in the amyloid precursor protein(APP)and presenilin 1(PS1)genes.Using untargeted lipidomics and sterolomics techniques,we investigated the metabolic profiles of lipids,with a focus on sterols specifically,in three brain regions:cerebellum,hippocampus,and olfactory bulb.Our results revealed significant alterations in various lipids,particularly in the hippocampus and olfactory bulb,suggesting changes in energy levels in these regions.Further pathway analysis indicated notable disruptions in key metabolic processes,particularly those related to fatty acids and cell membrane components.Additionally,we observed decreased expression of 15 genes involved in lipid and sterol regulation.Collectively,these findings provide new insights into how imbalances in lipid and sterol metabolism may contribute to the progression of Alzheimer’s disease,highlighting potential metabolic pathways involved in the development of this debilitating disease.
基金supported by a grant from the Strategic CAS Project(XDB38000000)a grant from the National Natural Science Foundation of China(81561128018).
文摘Lipoprotein,especially high-density lipoprotein(HDL),particles are composed of multiple heterogeneous subgroups containing various proteins and lipids.The molecular distribution among these subgroups is closely related to cardiovascular disease(CVD).Here,we established high-resolution proteomics and lipidomics(HiPL)methods to depict the molecular profiles across lipoprotein(Lipo-HiPL)and HDL(HDL-HiPL)subgroups by optimizing the resolution of anion-exchange chromatography and comprehensive quantification of proteins and lipids on the omics level.Furthermore,based on the Pearson correlation coefficient analysis of molecular profiles across high-resolution subgroups,we achieved the relationship of proteome–lipidome connectivity(PLC)for lipoprotein and HDL particles.By application of these methods to high-fat,high-cholesterol diet-fed rabbits and acute coronary syndrome(ACS)patients,we uncovered the delicate dynamics of the molecular profile and reconstruction of lipoprotein and HDL particles.Of note,the PLC features revealed by the HDL-HiPL method discriminated ACS from healthy individuals better than direct proteome and lipidome quantification or PLC features revealed by the Lipo-HiPL method,suggesting their potential in ACS diagnosis.Together,we established HiPL methods to trace the dynamics of the molecular profile and PLC of lipoprotein and even HDL during the development of CVD.
文摘Lipids,once thought to be mainly for energy-storage and structural purpose,have now gained immense recognition as a class of critical metabolites with versatile functions.The diversity and complexity of the cellular lipids are the main challenge for the comprehensive analysis of a lipidome.Lipidomics,which aims at mapping all of the lipids in a cell,is expanded rapidly in recent years,mainly attributed to recent advances in mass spectrometry(MS).MS-based lipidomic approaches developed recently allow the quick profiling of hundreds of lipids in a crude lipid extract.With the aid of latest computational tools/software(chemometrics),aberrant lipid metabolites or important signaling lipid(s)could be easily identified using unbiased lipid profiling approaches.Further tandem MS(MS/MS)-based lipidomic approaches,known as targeted approaches and able to convey structural information,hold the promise for highthroughput lipidome analysis.In this review,I discussed the basic strategy for systems level analysis of lipidome in biomedical study.
基金the support from the National Science Foundation(CBET-2112201)。
文摘The SH-SY5Y,neuroblastoma cell line,is a common in vitro model used to study physiological neuronal function and the neuronal response to different stimuli,including exposure to toxic chemicals.These cells can be differentiated to neuron-like cells by administration of various reagents,including retinoic acid or phorbol12-myristate-13-acetate.Despite their common use,there is an incomplete understanding of the molecular changes that occur during differentiation.Therefore,there is a critical need to fully understand the molecular changes that occur during differentiation to properly study neurotoxicity in response to various environmental exposures.Previous studies have investigated the proteome and transcriptome during differentiation;however,the regulation of the cellular lipidome in this process is unexplored.In this work,we conducted liquid chromatography−mass spectrometry(LC−MS)-based untargeted lipidomics in undifferentiated and differentiated SH-SY5Y cells,induced by retinoic acid.We show that there are global differences between the cellular lipidomes of undifferentiated and differentiated cells.Out of thousands of features detected in positive and negative electrospray ionization modes,44 species were identified that showed significant differences(p-value≤0.05,fold change≥2)in differentiated cells.Identification of these features combined with targeted lipidomics highlighted the accumulation of phospholipids,sterols,and sphingolipids during differentiation while triacylglycerols were depleted.These results provide important insights into lipid-related changes that occur during cellular differentiation of SH-5YSY cells and emphasize the need for the detailed characterization of biochemical differences that occur during differentiation while using this in vitro model for assessing ecological impacts of environmental pollutants.
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.
