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
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
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
Type 2 diabetes mellitus(T2DM)is one of the most prevalent chronic metabolic disorder characterized by insulin resistance and relative insulin deficiency.PPARδactivation has been reported to have several beneficial e...Type 2 diabetes mellitus(T2DM)is one of the most prevalent chronic metabolic disorder characterized by insulin resistance and relative insulin deficiency.PPARδactivation has been reported to have several beneficial effects in alleviating dyslipidemia and insulin resistance.GW501516,a synthetic PPARδagonist,was developed to target hyperlipidemia and reported to alleviating insulin resistance in T2DM.Studies indicate that PPARδactivation by GW501516 can reduce adiposity,enhanceβ-oxidation of fatty acids,and improve insulin sensitivity in T2DM animal models.Despite its therapeutic promise,potential carcinogenic effects also have been reported.Therefore,a comprehensive non-targeted and targeted lipidomics study was carried out to evaluate the regulatory effect of GW501516 in the plasma of db/db mice.The results revealed that GW501516 is effective in reducing the accumulation of lipids in the fatty acid metabolism pathway and lipid classes including triglycerides and phosphatidylglycerols.Furthermore,activation of PPARδby GW501516 demonstrated a beneficial effect on improving circulating cholesterol homeostasis.However,while the levels of hexosylceramides and sphingomyelin were partially reversed,ceramide levels,which are negatively associated with insulin sensitivity,were significantly elevated by GW501516.Despite these mixed outcomes,the study highlights both the promising therapeutic potential of PPARδactivation in metabolic disorders and the safety concerns regarding long-term clinical use.The findings provide valuable insights into the impact of GW501516-induced PPARδactivation on lipid metabolism in T2DM,contributing to a better understanding of its therapeutic potential and risks.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
Lipidomics is an emerging discipline that systematically studies the various types,functions,and metabolic pathways of lipids within living organisms.This field compares changes in diseases or drug impact,identifying ...Lipidomics is an emerging discipline that systematically studies the various types,functions,and metabolic pathways of lipids within living organisms.This field compares changes in diseases or drug impact,identifying biomarkers and molecular mechanisms present in lipid metabolic networks across different physiological or pathological states.Through employing analytical chemistry within the realm of lipidomics,researchers analyze traditional Chinese medicine(TCM).This analysis aids in uncovering potential mechanisms for treating diverse physiopathological conditions,assessing drug efficacy,understanding mechanisms of action and toxicity,and generating innovative ideas for disease prevention and treatment.This manuscript assesses recent literature,summarizing existing lipidomics technologies and their applications in TCM research.It delineates the efficacy,mechanisms,and toxicity research related to lipidomics in Chinese medicine.Additionally,it explores the utilization of lipidomics in quality control research for Chinese medicine,aiming to expand the application of lipidomics within this field.Ultimately,this initiative seeks to foster the integration of traditional medicine theory with modern science and technology,promoting an organic fusion between the two domains.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
Cadmium accumulation in seafood has become a major concern for human health.Recently,there has been an increasing focus on the potential risks associated with food-borne fluorescent carbon dots(CDs)that are formed dur...Cadmium accumulation in seafood has become a major concern for human health.Recently,there has been an increasing focus on the potential risks associated with food-borne fluorescent carbon dots(CDs)that are formed during the thermal processing of seafood.The co-occurrence of cadmium and CDs from cooked seafood become a common phenomenon and co-exposure of them to human has been an inevitable route during long-term seafood consuming.In addition,it has been widely recognized that CDs can be used as nanocarriers for metal ion chelation for their transport into organisms,thereby,they could influence the bioavailability of metal ion.While there have been numerous studies on the toxic effects of cadmium or CDs,none have explored the combined toxicity of food-borne CDs from clams(CCDs)and Cd^(2+).In this study,we investigated the single or co-exposure(combined exposure)of Cd^(2+)and CCDs on PC12 cells to investigate the combined toxicity of them.Our analysis of cell viability revealed that CCDs significantly augmented the cytotoxicity induced by Cd^(2+).More in-depth metabolomics and lipidomics investigation indicated that the combined exposure of Cd^(2+)and CCDs led to significant metabolic disorders,causing an antagonistic effect on energy metabolism,and a synergistic effect on amino acids and lipids metabolism.The disturbance in metabolomics and lipidomics was further supported by the disruption of mitochondrial membrane potential and the accumulation of reactive oxygen species following co-exposure.These findings provide new evidence that support the enhanced cytotoxicity of Cd^(2+)by the CCDs derived from the thermal processing of clams.This study also declares the necessary that prioritize the investigation of the potential impact of other thermal processing hazards originating from heat-processed foods on the toxicity of heavy metal ions.展开更多
As more and more studies have shown that lipid molecules play an important role in the whole biology,in-depth analysis of lipid structure has become particularly important in lipidomics.Mass spectrometry(MS),as the pr...As more and more studies have shown that lipid molecules play an important role in the whole biology,in-depth analysis of lipid structure has become particularly important in lipidomics.Mass spectrometry(MS),as the preferred tool for lipid analysis,has greatly promoted the development of this field.However,the existing MS methods still face many difficulties in the in-depth or even comprehensive analysis of lipid structure.In this review,we discuss recent advances in MS methods based on double bond-specific chemistries for the resolving of C=C location and geometry isomers of lipids.This progress has greatly advanced the lipidomics analysis to a deeper structural level and facilitated the development of structural lipid biology.展开更多
Dietary phosphatidylcholine(PC)is an ideal source of bioactive lipids showing efficacy to alleviate nonalcoholic fatty liver disease(NAFLD).In this study,the lipidomic profiles of nonalcoholic steatosis in mice and He...Dietary phosphatidylcholine(PC)is an ideal source of bioactive lipids showing efficacy to alleviate nonalcoholic fatty liver disease(NAFLD).In this study,the lipidomic profiles of nonalcoholic steatosis in mice and HepG2 cells treated with PC isolated from eggs(EPC)and soybean(SPC)were evaluated.EPC and SPC could significantly ameliorate fatty liver disease by down-regulating triglyceride(TG)and diglyceride(DG)levels.Remarkably,EPC exhibited better performance in regulating the hepatic lipid profile leading to decreased PC and TG,ceramides,phosphatidylethanolamine and phosphatidylserine levels.A total of 117 and 20 lipid biomarkers in liver and HepG2 cells involved in glycerophospholipid metabolism were screened out,respectively.The regulatory mechanism of EPC may be attributed to a decrease in the expression of ACACA and SREBP-1c.EPC,via suppressing lipogenic gene expression,which was superior to that of SPC in alleviating nonalcoholic steatosis.Overall,EPC and SPC attenuated HFD-induced NAFLD by improving the hepatic lipid profile.The more significant effect observed with EPC may be attributed to its modulation of glycerophospholipid metabolism.展开更多
That herbs with the"hot"property used to treat"cold"syndromes is a guiding principle of clinical prescription and medication in traditional Chinese medicine(TCM).However,this theory of TCM is still...That herbs with the"hot"property used to treat"cold"syndromes is a guiding principle of clinical prescription and medication in traditional Chinese medicine(TCM).However,this theory of TCM is still in the‘black box'stage,and few in-depth studies have examined the biological mechanisms underpinning the hot properties of herbs.展开更多
Alternate wetting and soil drying irrigation(AWD)technique is crucial in infuencing grain quality in rice(Oryza sativa L.).Lipids are the third most abundant constituents in rice grains,after starch and proteins,and a...Alternate wetting and soil drying irrigation(AWD)technique is crucial in infuencing grain quality in rice(Oryza sativa L.).Lipids are the third most abundant constituents in rice grains,after starch and proteins,and are closely related to grain quality.However,it remains unclear about the changes in lipids profling under different AWD regimes.This study set up three irrigation regimes including conventional irrigation(CI),alternate wetting and moderate soil drying irrigation(AWMD),and alternate wetting and severe soil drying irrigation(AWSD).It explored lipidome changes in milled rice of Yangdao 6(YD6)using the untargeted lipidomics approach and analyzed rice cooking and eating quality.The results identifed seven lipid classes,55 lipid subclasses,and 1,086 lipid molecular species.Compared with the CI regime,the AWMD regime mainly altered lipid subclasses consisting of triglyceride(TG),ceramide(Cer),diglyceride(DG),bis-methyl lysophosphatidic acid(BisMePA),phosphocholine(PC),phosphoethanolamine(PE),monogalactosyldiacylglycerol(MGDG),and digalactosyl diglyceride(DGDG)in milled rice and improved cooking and eating quality of rice;in contrast,the AWSD regime distinctly changed lipid subclasses like TG,Cer,DG,PC,PE,hexosylceramide(Hex1Cer),DGDG,and BisMePA and degraded cooking and eating quality of rice.Specifcally,AWMD most signifcantly altered the expressions of lipid molecules,including DGDG(18:0_18:2),DGDG(16:0_14:0),PC(33:1),Cer(t17:0_26:0),and Cer(t17:0_16:0);AWSD most obviously influenced the expressions of TG(6:0_14:0_18:3),PC(41:1),TG(19:1_18:4_18:4),Hex1Cer(d18:2_24:0+O),and Hex1Cer(d18:2_24:1).These 10 altered lipid molecules in milled rice can be preferentially used for investigating their relationships with grain quality in rice.展开更多
Mass spectrometry(MS)-based omics technologies are now widely used to profile small molecules in multiple matrices to confer comprehensive snapshots of cellular metabolic phenotypes.The metabolomes of cells,tissues,an...Mass spectrometry(MS)-based omics technologies are now widely used to profile small molecules in multiple matrices to confer comprehensive snapshots of cellular metabolic phenotypes.The metabolomes of cells,tissues,and organisms comprise a variety of molecules including lipids,amino acids,sugars,organic acids,and so on.Metabolomics mainly focus on the hydrophilic classes,while lipidomics has emerged as an independent omics owing to the complexities of the organismal lipidomes.The potential roles of lipids and small metabolites in disease pathogenesis have been widely investigated in various human diseases,but system-level understanding is largely lacking,which could be partly attributed to the insufficiency in terms of metabolite coverage and quantitation accuracy in current analytical technologies.While scientists are continuously striving to develop high-coverage omics approaches,integration of metabolomics and lipidomics is becoming an emerging approach to mechanistic investigation.Integration of metabolome and lipidome offers a complete atlas of the metabolic landscape,enabling comprehensive network analysis to identify critical metabolic drivers in disease pathology,facilitating the study of interconnection between lipids and other metabolites in disease progression.In this review,we summarize omics-based findings on the roles of lipids and metabolites in the pathogenesis of selected major diseases threatening public health.We also discuss the advantages of integrating lipidomics and metabolomics for in-depth understanding of molecular mechanism in disease pathogenesis.展开更多
Lipidomics, which targets at the construction of a comprehensive map of lipidome comprising the entire lipid pool within a cell or tissue, is currently emerging as an independent discipline at the interface of lipid b...Lipidomics, which targets at the construction of a comprehensive map of lipidome comprising the entire lipid pool within a cell or tissue, is currently emerging as an independent discipline at the interface of lipid biology, technology and medicine. The diversity and complexity of the biological lipidomes call for technical innovation and improvement to meet the needs of various biomedical studies. The recent wave of expansion in the field of lipidomic research is mainly attributed to advances in analytical technologies, in particular, the development of new mass spectrometric and chromatographic tools for the characterization and quantification of the wide array of diverse lipid species in the cellular lipidome. Here, we review some of the key technical advances in lipidome analysis and put forth the applications of lipidomics in addressing the biological roles of lipids in numerous disease models including the metabolic syndrome, neurodegenerative diseases and infectious diseases, as well as the increasing urgency to construct the lipidome inventory for various mammalian/organism models useful for biomedical research.展开更多
Lipotoxicity, caused by intracellular lipid accumulation, accelerates the degenerative process of cellular senescence, which has implications in cancer development and therapy. Previously, carnitine palmitoyltransfera...Lipotoxicity, caused by intracellular lipid accumulation, accelerates the degenerative process of cellular senescence, which has implications in cancer development and therapy. Previously, carnitine palmitoyltransferase 1C(CPT1C), a mitochondrial enzyme that catalyzes carnitinylation of fatty acids, was found to be a critical regulator of cancer cell senescence. However, whether loss of CPT1C could induce senescence as a result of lipotoxicity remains unknown. An LC/MS-based lipidomic analysis of PANC-1,MDA-MB-231, HCT-116 and A549 cancer cells was conducted after siRNA depletion of CPT1C. Cellular lipotoxicity was further confirmed by lipotoxicity assays. Significant changes were found in the lipidome of CPT1C-depleted cells, including major alterations in fatty acid, diacylglycerol, triacylglycerol, oxidative lipids, cardiolipin, phosphatidylglycerol, phosphatidylcholine/phosphatidylethanolamine ratio and sphingomyelin. This was coincident with changes in expressions of mRNAs involved in lipogenesis.Histological and biochemical analyses revealed higher lipid accumulation and increased malondialdehyde and reactive oxygen species, signatures of lipid peroxidation and oxidative stress. Reduction of ATP synthesis, loss of mitochondrial transmembrane potential and down-regulation of expression of mitochondriogenesis gene m RNAs indicated mitochondrial dysfunction induced by lipotoxicity, which could further result in cellular senescence. Taken together, this study demonstrated CPT1C plays a critical role in the regulation of cancer cell lipotoxicity and cell senescence, suggesting that inhibition of CPT1C may serve as a new therapeutic strategy through induction of tumor lipotoxicity and senescence.展开更多
Lipid remodeling is crucial for cold tolerance in plants.However,the precise alternations of lipidomics during cold responses remain elusive,especially in maize(Zea mays L.).In addition,the key genes responsible for c...Lipid remodeling is crucial for cold tolerance in plants.However,the precise alternations of lipidomics during cold responses remain elusive,especially in maize(Zea mays L.).In addition,the key genes responsible for cold tolerance in maize lipid metabolism have not been identified.Here,we integrate lipidomic,transcriptomic,and genetic analysis to determine the profile of lipid remodeling caused by cold stress.We find that the homeostasis of cellular lipid metabolism is essential for maintaining cold tolerance of maize.Also,we detect 210 lipid species belonging to 13 major classes,covering phospholipids,glycerides,glycolipids,and free fatty acids.Various lipid metabolites undergo specific and selective alterations in response to cold stress,especially mono-/di-unsaturated lysophosphatidic acid,lysophosphatidylcholine,phosphatidylcholine,and phosphatidylinositol,as well as polyunsaturated phosphatidic acid,monogalactosyldiacylglycerol,diacylglycerol,and triacylglycerol.In addition,we identify a subset of key enzymes,including ketoacyl-acyl-carrier protein synthase II(KAS II),acyl-carrier protein 2(ACP2),male sterility33(Ms33),and stearoyl-acyl-carrier protein desaturase 2(SAD2)involved in glycerolipid biosynthetic pathways are positive regulators of maize cold tolerance.These results reveal a comprehensive lipidomic profile during the cold response of maize and provide genetic resources for enhancing cold tolerance in crops.展开更多
Non-alcoholic fatty liver disease(NAFLD),the most common chronic liver disorder in Western countries,comprises steatosis to nonalcoholic steatohepatitis(NASH),with the latter having the potential to progress to cirrho...Non-alcoholic fatty liver disease(NAFLD),the most common chronic liver disorder in Western countries,comprises steatosis to nonalcoholic steatohepatitis(NASH),with the latter having the potential to progress to cirrhosis.The transition from isolated steatosis to NASH is still poorly understood,but lipidomics approach revealed that the hepatic lipidome is extensively altered in the setting of steatosis and steatohepatitis and these alterations correlate with disease progression.Recent data suggest that both quantity and quality of the accumulated lipids are involved in pathogenesis of NAFLD.Changes in glycerophospholipid,sphingolipid,and fatty acid composition have been described in both liver biopsies and plasma of patients with NAFLD,implicating that specific lipid species are involved in oxidative stress,inflammation,and cell death.In this article,we summarize the findings of main human lipidomics studies in NAFLD and delineate the currently available information on the pathogenetic role of each lipid class in lipotoxicity and disease progression.展开更多
The circadian timing system plays a key role in orchestrating lipid metabolism. In concert with the solar cycle, the circadian system ensures that daily rhythms in lipid absorption, storage, and transport are temporal...The circadian timing system plays a key role in orchestrating lipid metabolism. In concert with the solar cycle, the circadian system ensures that daily rhythms in lipid absorption, storage, and transport are temporally coordinated with rest-activity and feeding cycles. At the cellular level, genes involved in lipid synthesis and fatty acid oxidation are rhythmically activated and repressed by core clock proteins in a tissue-specific manner. Consequently, loss of clock gene function or misalignment of circadian rhythms with feeding cycles （e.g., in shift work） results in impaired lipid homeostasis. Herein, we review recent progress in circadian rhythms research using lipidomics, i.e., large-scale profiling of lipid metabolites, to characterize circadian-regulated lipid pathways in mammals. In mice, novel regulatory circuits involved in fatty acid metabolism have been identified in adipose tissue, liver, and muscle. Extensive diversity in circadian regulation of plasma lipids has also been revealed in humans using lipidomics and other metabolomics approaches. In future studies, lipidomics platforms will be increasingly used to better understand the effects of genetic variation, shift work, food intake, and drugs on circadian-regulated lipid pathways and metabolic health.展开更多
Palm oil is currently the leading edible oil consumed worldwide. Triacylglycerol （TAG） and diacylglycerol （DAG） are the dominant lipid classes in palm oil. Other lipid classes present in crude palm oil, such as ph...Palm oil is currently the leading edible oil consumed worldwide. Triacylglycerol （TAG） and diacylglycerol （DAG） are the dominant lipid classes in palm oil. Other lipid classes present in crude palm oil, such as phospholipids and galactolipids, are very low in abundance. These low-abundance lipids constitute key intermediates in lipid biosynthesis. In this study, we applied multiple lipidomic approaches, including high-sensitivity and high-specificity multiple reaction monitoring, to comprehensively quantify individual lipid species in crude palm oil. We also established a new liquid chromatography-coupled mass spectrometry method that allows direct quantification of low-abundance galactolipids in palm oil without the need for sample pretreatrnent. As crude palm oil contains large amounts of neutral lipids, our direct-detection method circumvents many of the challenges encountered with conventional lipid quantification methods. This approach allows direct measurement of lipids with no hassle during sample preparation and is more accurate and precise compared with other methods.展开更多
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(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the financial support by Hong Kong Research Grants Council(No.T12-101/23-N)National Natural Science Foundation of China(No.22206160)。
文摘Type 2 diabetes mellitus(T2DM)is one of the most prevalent chronic metabolic disorder characterized by insulin resistance and relative insulin deficiency.PPARδactivation has been reported to have several beneficial effects in alleviating dyslipidemia and insulin resistance.GW501516,a synthetic PPARδagonist,was developed to target hyperlipidemia and reported to alleviating insulin resistance in T2DM.Studies indicate that PPARδactivation by GW501516 can reduce adiposity,enhanceβ-oxidation of fatty acids,and improve insulin sensitivity in T2DM animal models.Despite its therapeutic promise,potential carcinogenic effects also have been reported.Therefore,a comprehensive non-targeted and targeted lipidomics study was carried out to evaluate the regulatory effect of GW501516 in the plasma of db/db mice.The results revealed that GW501516 is effective in reducing the accumulation of lipids in the fatty acid metabolism pathway and lipid classes including triglycerides and phosphatidylglycerols.Furthermore,activation of PPARδby GW501516 demonstrated a beneficial effect on improving circulating cholesterol homeostasis.However,while the levels of hexosylceramides and sphingomyelin were partially reversed,ceramide levels,which are negatively associated with insulin sensitivity,were significantly elevated by GW501516.Despite these mixed outcomes,the study highlights both the promising therapeutic potential of PPARδactivation in metabolic disorders and the safety concerns regarding long-term clinical use.The findings provide valuable insights into the impact of GW501516-induced PPARδactivation on lipid metabolism in T2DM,contributing to a better understanding of its therapeutic potential and risks.
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funded by the Sanming Project of Medicine in Shenzhen,China(Grant No.:SZZYSM202106004)the National Natural Science Foundation of China(Grant No.:82272960)+1 种基金the Shenzhen Science and Technology Innovation Commission,China(Grant No.:JCYJ20210324142012033)the Scientific Research Project of Guangdong Provincial Bureau of Traditional Chinese Medicine,China(Grant No.:20252037).
文摘Lipidomics is an emerging discipline that systematically studies the various types,functions,and metabolic pathways of lipids within living organisms.This field compares changes in diseases or drug impact,identifying biomarkers and molecular mechanisms present in lipid metabolic networks across different physiological or pathological states.Through employing analytical chemistry within the realm of lipidomics,researchers analyze traditional Chinese medicine(TCM).This analysis aids in uncovering potential mechanisms for treating diverse physiopathological conditions,assessing drug efficacy,understanding mechanisms of action and toxicity,and generating innovative ideas for disease prevention and treatment.This manuscript assesses recent literature,summarizing existing lipidomics technologies and their applications in TCM research.It delineates the efficacy,mechanisms,and toxicity research related to lipidomics in Chinese medicine.Additionally,it explores the utilization of lipidomics in quality control research for Chinese medicine,aiming to expand the application of lipidomics within this field.Ultimately,this initiative seeks to foster the integration of traditional medicine theory with modern science and technology,promoting an organic fusion between the two domains.
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.
基金supported by the National Key Research and Development Project of China(2017YFC1600702)the Central Funds Guiding the Local Science and Technology Development of China(2020JH6/10500002).
文摘Cadmium accumulation in seafood has become a major concern for human health.Recently,there has been an increasing focus on the potential risks associated with food-borne fluorescent carbon dots(CDs)that are formed during the thermal processing of seafood.The co-occurrence of cadmium and CDs from cooked seafood become a common phenomenon and co-exposure of them to human has been an inevitable route during long-term seafood consuming.In addition,it has been widely recognized that CDs can be used as nanocarriers for metal ion chelation for their transport into organisms,thereby,they could influence the bioavailability of metal ion.While there have been numerous studies on the toxic effects of cadmium or CDs,none have explored the combined toxicity of food-borne CDs from clams(CCDs)and Cd^(2+).In this study,we investigated the single or co-exposure(combined exposure)of Cd^(2+)and CCDs on PC12 cells to investigate the combined toxicity of them.Our analysis of cell viability revealed that CCDs significantly augmented the cytotoxicity induced by Cd^(2+).More in-depth metabolomics and lipidomics investigation indicated that the combined exposure of Cd^(2+)and CCDs led to significant metabolic disorders,causing an antagonistic effect on energy metabolism,and a synergistic effect on amino acids and lipids metabolism.The disturbance in metabolomics and lipidomics was further supported by the disruption of mitochondrial membrane potential and the accumulation of reactive oxygen species following co-exposure.These findings provide new evidence that support the enhanced cytotoxicity of Cd^(2+)by the CCDs derived from the thermal processing of clams.This study also declares the necessary that prioritize the investigation of the potential impact of other thermal processing hazards originating from heat-processed foods on the toxicity of heavy metal ions.
基金financially supported by the National Natural Science Foundation of China(No.22074111)National Key Research and Development Program of China(No.2021YFC2700700)the Opening fund of Hubei Key Laboratory of Bioinorganic Chemistry&Materia Medica(No.BCMM202303)。
文摘As more and more studies have shown that lipid molecules play an important role in the whole biology,in-depth analysis of lipid structure has become particularly important in lipidomics.Mass spectrometry(MS),as the preferred tool for lipid analysis,has greatly promoted the development of this field.However,the existing MS methods still face many difficulties in the in-depth or even comprehensive analysis of lipid structure.In this review,we discuss recent advances in MS methods based on double bond-specific chemistries for the resolving of C=C location and geometry isomers of lipids.This progress has greatly advanced the lipidomics analysis to a deeper structural level and facilitated the development of structural lipid biology.
基金supported by the Shanxi Provincial General Program for Basic Research Project(202303021211093)the National Natural Science Foundation of China(31960492)+1 种基金Key R&D projects in Shanxi Province(202102140601017)Shanxi Agricultural University High-Level Talent Project(2021XG013)。
文摘Dietary phosphatidylcholine(PC)is an ideal source of bioactive lipids showing efficacy to alleviate nonalcoholic fatty liver disease(NAFLD).In this study,the lipidomic profiles of nonalcoholic steatosis in mice and HepG2 cells treated with PC isolated from eggs(EPC)and soybean(SPC)were evaluated.EPC and SPC could significantly ameliorate fatty liver disease by down-regulating triglyceride(TG)and diglyceride(DG)levels.Remarkably,EPC exhibited better performance in regulating the hepatic lipid profile leading to decreased PC and TG,ceramides,phosphatidylethanolamine and phosphatidylserine levels.A total of 117 and 20 lipid biomarkers in liver and HepG2 cells involved in glycerophospholipid metabolism were screened out,respectively.The regulatory mechanism of EPC may be attributed to a decrease in the expression of ACACA and SREBP-1c.EPC,via suppressing lipogenic gene expression,which was superior to that of SPC in alleviating nonalcoholic steatosis.Overall,EPC and SPC attenuated HFD-induced NAFLD by improving the hepatic lipid profile.The more significant effect observed with EPC may be attributed to its modulation of glycerophospholipid metabolism.
基金supported by the Chief Scientist of Qi-Huang Project of the National Traditional Chinese Medicine Inheritance and Innovation“One Hundred Million”Talent Project,China(Grant No.:[2021]No.7)the National Famous Old Traditional Chinese Medicine Experts Inheritance Studio Construction Program of National Administration of Traditional Chinese Medicine,China(Grant No.:[2022]No.75)+3 种基金the Seventh Batch of National Famous Old Traditional Chinese Medicine Experts Experience Heritage Construction Program of National Administration of Traditional Chinese Medicine,China(Grant No.:[2022]No.76)Heilongjiang Touyan Innovation Team Program,China(Grant No.:[2019]No.5)the Natural Science Foundation of Zhejiang Province(Grant No.:LQN25H280009)the Research Project of Zhejiang Chinese Medical University,China(Grant No.:2023RCZXZK22).
文摘That herbs with the"hot"property used to treat"cold"syndromes is a guiding principle of clinical prescription and medication in traditional Chinese medicine(TCM).However,this theory of TCM is still in the‘black box'stage,and few in-depth studies have examined the biological mechanisms underpinning the hot properties of herbs.
基金supported by the Natural Science Foundation of Jiangsu Province,China(BK20241931 and BK20221371)the National Natural Science Foundation of China(32071943 and 32372214)the National Key Research and Development Program of China(2022YFD2300304)。
文摘Alternate wetting and soil drying irrigation(AWD)technique is crucial in infuencing grain quality in rice(Oryza sativa L.).Lipids are the third most abundant constituents in rice grains,after starch and proteins,and are closely related to grain quality.However,it remains unclear about the changes in lipids profling under different AWD regimes.This study set up three irrigation regimes including conventional irrigation(CI),alternate wetting and moderate soil drying irrigation(AWMD),and alternate wetting and severe soil drying irrigation(AWSD).It explored lipidome changes in milled rice of Yangdao 6(YD6)using the untargeted lipidomics approach and analyzed rice cooking and eating quality.The results identifed seven lipid classes,55 lipid subclasses,and 1,086 lipid molecular species.Compared with the CI regime,the AWMD regime mainly altered lipid subclasses consisting of triglyceride(TG),ceramide(Cer),diglyceride(DG),bis-methyl lysophosphatidic acid(BisMePA),phosphocholine(PC),phosphoethanolamine(PE),monogalactosyldiacylglycerol(MGDG),and digalactosyl diglyceride(DGDG)in milled rice and improved cooking and eating quality of rice;in contrast,the AWSD regime distinctly changed lipid subclasses like TG,Cer,DG,PC,PE,hexosylceramide(Hex1Cer),DGDG,and BisMePA and degraded cooking and eating quality of rice.Specifcally,AWMD most signifcantly altered the expressions of lipid molecules,including DGDG(18:0_18:2),DGDG(16:0_14:0),PC(33:1),Cer(t17:0_26:0),and Cer(t17:0_16:0);AWSD most obviously influenced the expressions of TG(6:0_14:0_18:3),PC(41:1),TG(19:1_18:4_18:4),Hex1Cer(d18:2_24:0+O),and Hex1Cer(d18:2_24:1).These 10 altered lipid molecules in milled rice can be preferentially used for investigating their relationships with grain quality in rice.
基金funded by National Key R&D Program of China (2018YFA0800901,2018YFA0506902)The Strategic Priority Research Program of the Chinese Academy of Sciences (XDA12030211)National Natural Science Foundation of China (31671226,31871194).
文摘Mass spectrometry(MS)-based omics technologies are now widely used to profile small molecules in multiple matrices to confer comprehensive snapshots of cellular metabolic phenotypes.The metabolomes of cells,tissues,and organisms comprise a variety of molecules including lipids,amino acids,sugars,organic acids,and so on.Metabolomics mainly focus on the hydrophilic classes,while lipidomics has emerged as an independent omics owing to the complexities of the organismal lipidomes.The potential roles of lipids and small metabolites in disease pathogenesis have been widely investigated in various human diseases,but system-level understanding is largely lacking,which could be partly attributed to the insufficiency in terms of metabolite coverage and quantitation accuracy in current analytical technologies.While scientists are continuously striving to develop high-coverage omics approaches,integration of metabolomics and lipidomics is becoming an emerging approach to mechanistic investigation.Integration of metabolome and lipidome offers a complete atlas of the metabolic landscape,enabling comprehensive network analysis to identify critical metabolic drivers in disease pathology,facilitating the study of interconnection between lipids and other metabolites in disease progression.In this review,we summarize omics-based findings on the roles of lipids and metabolites in the pathogenesis of selected major diseases threatening public health.We also discuss the advantages of integrating lipidomics and metabolomics for in-depth understanding of molecular mechanism in disease pathogenesis.
基金supported by the grants to G.S.from Chinese Academy of Sciences(Nos.KYQY-162 and Y265091891)
文摘Lipidomics, which targets at the construction of a comprehensive map of lipidome comprising the entire lipid pool within a cell or tissue, is currently emerging as an independent discipline at the interface of lipid biology, technology and medicine. The diversity and complexity of the biological lipidomes call for technical innovation and improvement to meet the needs of various biomedical studies. The recent wave of expansion in the field of lipidomic research is mainly attributed to advances in analytical technologies, in particular, the development of new mass spectrometric and chromatographic tools for the characterization and quantification of the wide array of diverse lipid species in the cellular lipidome. Here, we review some of the key technical advances in lipidome analysis and put forth the applications of lipidomics in addressing the biological roles of lipids in numerous disease models including the metabolic syndrome, neurodegenerative diseases and infectious diseases, as well as the increasing urgency to construct the lipidome inventory for various mammalian/organism models useful for biomedical research.
基金supported by the National Key Research and Development Program of China (Grant No. 2017YFE0109900)the National Natural Science Foundation of China (Grant Nos. 82025034 and 81973392)+5 种基金the Shenzhen Science and Technology Program (Grant No. KQTD20190929174023858)the Natural Science Foundation of Guangdong (Grant No. 2017A030311018)the 111 project (Grant No. B16047)the Key Laboratory Foundation of Guangdong Province (Grant No. 2017B030314030)the Local Innovative and Research Teams Project of Guangdong Pearl River Talents Program (Grant No. 2017BT01Y093)the National Engineering and Technology Research Center for New drug Druggability Evaluation (Seed Program of Guangdong Province, Grant No. 2017B090903004)。
文摘Lipotoxicity, caused by intracellular lipid accumulation, accelerates the degenerative process of cellular senescence, which has implications in cancer development and therapy. Previously, carnitine palmitoyltransferase 1C(CPT1C), a mitochondrial enzyme that catalyzes carnitinylation of fatty acids, was found to be a critical regulator of cancer cell senescence. However, whether loss of CPT1C could induce senescence as a result of lipotoxicity remains unknown. An LC/MS-based lipidomic analysis of PANC-1,MDA-MB-231, HCT-116 and A549 cancer cells was conducted after siRNA depletion of CPT1C. Cellular lipotoxicity was further confirmed by lipotoxicity assays. Significant changes were found in the lipidome of CPT1C-depleted cells, including major alterations in fatty acid, diacylglycerol, triacylglycerol, oxidative lipids, cardiolipin, phosphatidylglycerol, phosphatidylcholine/phosphatidylethanolamine ratio and sphingomyelin. This was coincident with changes in expressions of mRNAs involved in lipogenesis.Histological and biochemical analyses revealed higher lipid accumulation and increased malondialdehyde and reactive oxygen species, signatures of lipid peroxidation and oxidative stress. Reduction of ATP synthesis, loss of mitochondrial transmembrane potential and down-regulation of expression of mitochondriogenesis gene m RNAs indicated mitochondrial dysfunction induced by lipotoxicity, which could further result in cellular senescence. Taken together, this study demonstrated CPT1C plays a critical role in the regulation of cancer cell lipotoxicity and cell senescence, suggesting that inhibition of CPT1C may serve as a new therapeutic strategy through induction of tumor lipotoxicity and senescence.
基金supported by grants from the State Key Project of Research and Development Plan(2022YFF1001603)the National Natural Science Foundation of China(32022008,32272025,and 31921001)the Chinese Universities Scientific Fund(2022TC137 and 2023TC019).
文摘Lipid remodeling is crucial for cold tolerance in plants.However,the precise alternations of lipidomics during cold responses remain elusive,especially in maize(Zea mays L.).In addition,the key genes responsible for cold tolerance in maize lipid metabolism have not been identified.Here,we integrate lipidomic,transcriptomic,and genetic analysis to determine the profile of lipid remodeling caused by cold stress.We find that the homeostasis of cellular lipid metabolism is essential for maintaining cold tolerance of maize.Also,we detect 210 lipid species belonging to 13 major classes,covering phospholipids,glycerides,glycolipids,and free fatty acids.Various lipid metabolites undergo specific and selective alterations in response to cold stress,especially mono-/di-unsaturated lysophosphatidic acid,lysophosphatidylcholine,phosphatidylcholine,and phosphatidylinositol,as well as polyunsaturated phosphatidic acid,monogalactosyldiacylglycerol,diacylglycerol,and triacylglycerol.In addition,we identify a subset of key enzymes,including ketoacyl-acyl-carrier protein synthase II(KAS II),acyl-carrier protein 2(ACP2),male sterility33(Ms33),and stearoyl-acyl-carrier protein desaturase 2(SAD2)involved in glycerolipid biosynthetic pathways are positive regulators of maize cold tolerance.These results reveal a comprehensive lipidomic profile during the cold response of maize and provide genetic resources for enhancing cold tolerance in crops.
文摘Non-alcoholic fatty liver disease(NAFLD),the most common chronic liver disorder in Western countries,comprises steatosis to nonalcoholic steatohepatitis(NASH),with the latter having the potential to progress to cirrhosis.The transition from isolated steatosis to NASH is still poorly understood,but lipidomics approach revealed that the hepatic lipidome is extensively altered in the setting of steatosis and steatohepatitis and these alterations correlate with disease progression.Recent data suggest that both quantity and quality of the accumulated lipids are involved in pathogenesis of NAFLD.Changes in glycerophospholipid,sphingolipid,and fatty acid composition have been described in both liver biopsies and plasma of patients with NAFLD,implicating that specific lipid species are involved in oxidative stress,inflammation,and cell death.In this article,we summarize the findings of main human lipidomics studies in NAFLD and delineate the currently available information on the pathogenetic role of each lipid class in lipotoxicity and disease progression.
基金supported by the Duke-NUS Signature Research Program funded by the Agency for Science,Technology,and Research,Singapore,and the Ministry of Health,Singaporethe SingHealth Foundation(SHF),Singapore,under SHF/FG410P/2009
文摘The circadian timing system plays a key role in orchestrating lipid metabolism. In concert with the solar cycle, the circadian system ensures that daily rhythms in lipid absorption, storage, and transport are temporally coordinated with rest-activity and feeding cycles. At the cellular level, genes involved in lipid synthesis and fatty acid oxidation are rhythmically activated and repressed by core clock proteins in a tissue-specific manner. Consequently, loss of clock gene function or misalignment of circadian rhythms with feeding cycles （e.g., in shift work） results in impaired lipid homeostasis. Herein, we review recent progress in circadian rhythms research using lipidomics, i.e., large-scale profiling of lipid metabolites, to characterize circadian-regulated lipid pathways in mammals. In mice, novel regulatory circuits involved in fatty acid metabolism have been identified in adipose tissue, liver, and muscle. Extensive diversity in circadian regulation of plasma lipids has also been revealed in humans using lipidomics and other metabolomics approaches. In future studies, lipidomics platforms will be increasingly used to better understand the effects of genetic variation, shift work, food intake, and drugs on circadian-regulated lipid pathways and metabolic health.
文摘Palm oil is currently the leading edible oil consumed worldwide. Triacylglycerol （TAG） and diacylglycerol （DAG） are the dominant lipid classes in palm oil. Other lipid classes present in crude palm oil, such as phospholipids and galactolipids, are very low in abundance. These low-abundance lipids constitute key intermediates in lipid biosynthesis. In this study, we applied multiple lipidomic approaches, including high-sensitivity and high-specificity multiple reaction monitoring, to comprehensively quantify individual lipid species in crude palm oil. We also established a new liquid chromatography-coupled mass spectrometry method that allows direct quantification of low-abundance galactolipids in palm oil without the need for sample pretreatrnent. As crude palm oil contains large amounts of neutral lipids, our direct-detection method circumvents many of the challenges encountered with conventional lipid quantification methods. This approach allows direct measurement of lipids with no hassle during sample preparation and is more accurate and precise compared with other methods.
