Effect of replacement of soybean oil by Hermetia illucens fat on performance,digestibility,cecal microbiome,liver transcriptome and liver and plasma lipidomes of broilers

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.

Cyanidin-3-glucoside protects the photooxidative damage of retinal pigment epithelium cells by regulating sphingolipid signaling and inhibiting MAPK pathway

Cyanidin-3-glucoside(C3G)is the most common anthocyanin in dark grains and berries and is a food functional factor to improve visual health.However,the mechanisms of C3G on blue light-induced retinal pigment epithelial(RPE)cell photooxidative damage needs further exploration.We investigated the effects of C3G on blue light-irradiated A2E-containing RPE cells and explored whether sphingolipid,mitogen-activated protein kinase(MAPK),and mitochondria-mediated pathways are involved in this mechanism.Blue light irradiation led to mitochondria and lysosome damage in RPE cells,whereas C3G preserved mitochondrial morphology and function and maintained the lysosomal integrity.C3G suppressed the phosphorylation of JNK and p38 MAPK and mitochondria-mediated pathways to inhibit RPE cell apoptosis.Lipidomics data showed that C3G protected RPE cells against blue light-induced lipid peroxidation and apoptosis by maintaining sphingolipids balance.C3G significantly inhibited ceramide(Cer d18:0/15:0,Cer d18:0/16:0 and Cer d18:0/18:0)accumulation and elevated galactosylceramide(GalCer d18:1/15:0 and GalCer d18:1/16:0)levels in the irradiated A2E-containing RPE cells.Furthermore,C3G attenuated cell membrane damage by increasing phosphatidylcholine and phosphatidylserine levels.C3G inhibited apoptosis and preserved the structure of mitochondria and lysosome by regulating sphingolipid signaling and suppression of MAPK activation in RPE cells.Thus,dietary supplementation of C3G prevents retinal photooxidative damage.

Repeated inoculation with rumen fluid accelerates the rumen bacterial transition with no benefit on production performance in postpartum Holstein dairy cows

Background The dairy cow’s postpartum period is characterized by dramatic physiological changes,therefore imposing severe challenges on the animal for maintaining health and milk output.The dynamics of the ruminal microbiota are also tremendous and may play a crucial role in lactation launch.We aim to investigate the potential benefits of early microbial intervention by fresh rumen microbiota transplantation(RMT)and sterile RMT in postpartum dairy cows.Twelve fistulated peak-lactation dairy cows were selected to be the donors for rumen fluid collection.Thirty postpartum cows were divided into 3 groups as the transplantation receptors respectively receiving 10 L fresh rumen fluid(FR),10 L sterile rumen fluid(SR),or 10 L saline(CON)during 3 d after calving.Results Production performance,plasma indices,plasma lipidome,ruminal microbiome,and liver transcriptome were recorded.After fresh and sterile RMT,we found that the molar proportion of propionic acid was increased on d 7 in the FR and SR groups and the bacterial composition was also significantly changed when compared with the CON group.A similarity analysis showed that the similarities between the CON group and FR or SR group on d 7 were 48.40%or 47.85%,whereas the similarities between microbiota on d 7 and 21 in the FR and SR groups were 68.34%or 66.85%.Dry matter intake and feed efficiency were not affected by treatments.Plasmaβ-hydroxybutyrate concentration in the FR group was decreased and significantly different lipids mainly included phosphatidylcholine and lysophosphatidylcholine containing polyunsaturated fatty acids.Hepatic transcriptomics analysis indicated acutephase response pathways were upregulated in the SR group.Conclusions Our study suggests that RMT can shorten the transition process of the ruminal microbiota of postpartum dairy cows with no benefit on dry matter intake or feed efficiency.Inoculation with rumen fluid may not be a useful approach to promote the recovery of postpartum dairy cows.

Yolk free egg substitute improves the serum phospholipid profile of mice with metabolic syndrome based on lipidomic analysis

In this study,the impacts of egg consumption on mice model of metabolic syndrome(Met S)were comparatively investigated.Mice were divided into five groups(n=8):normal diet group(ND),high-fat diet group(HFD),HFD with whole egg group(WE),HFD with free-yolk egg substitute group(YFES),and HFD with lovastatin group(Lov).Main biochemical indexes and a non-targeted lipidomic analysis were employed to insight the lipid profile changes in serum.It was revealed that WE could significantly improve serum biochemical indexes by reducing body weight,low-density lipoprotein cholesterol(LDL-C)and total cholesterol(TC),while increasing high-density lipoprotein cholesterol.YFES exhibited remarkably better performance in increasing phosphatidylglycerol and phosphatidic acids,while decreasing phosphatidylinositol than WE.A total of 50 differential lipids biomarkers tightly related to glycerophospholipids metabolism were screened out.Carnitine C18:2 and C12:1,SM(d18:0/12:0),and SM(d18:1/14:1)were significantly upregulated in YFES compared to WE.YFES reduced expression of SREBP-1c and Cpt1a,while did not affect the expression of PPAR-α.Sphingomyelin biomarkers were positively related to the TC(|r|>0.6),while PPAR-αwas negatively correlated with triglyceride and LDL-C levels.To sum up,YFES attenuated HFD-induced Met S by improving the serum phospholipids,which account for its modulation of glycerophospholipid metabolism.

Integrating lipidomics and gut microbiota to study the anti-hyperlipidemia effect of Sargentodoxae Caulis extract

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.

Eight Zhes Decoction ameliorates the lipid dysfunction of nonalcoholic fatty liver disease using integrated lipidomics, network pharmacology and pharmacokinetics

Nonalcoholic fatty liver disease(NAFLD)has developed into the most common chronic liver disease and can lead to liver cancer.Our laboratory previously developed a novel prescription for NAFLD,“Eight Zhes Decoction”(EZD),which has shown good curative effects in clinical practice.However,the pharmacodynamic material basis and mechanism have not yet been revealed.A strategy integrating lipidomics,network pharmacology and pharmacokinetics was used to reveal the active components and mechanisms of EZD against NAFLD.The histopathological results showed that EZD attenuated the degrees of collagen deposition and steatosis in the livers of nonalcoholic steatofibrosis model mice.Furthermore,glycerophospholipid metabolism,arachidonic acid metabolism,glycerolipid metabolism and linoleic acid metabolism with phospholipase A2 group IVA(PLA2G4A)and cytochrome P450 as the core targets and 12,13-cis-epoxyoctadecenoic acid,12(S)-hydroxyeicosatetraenoic acid,leukotriene B4,prostaglandin E2,phosphatidylcholines(PCs)and triacylglycerols(TGs)as the main lipids were found to be involved in the treatment of NAFLD by EZD.Importantly,naringenin,artemetin,canadine,and bicuculline were identified as the active ingredients of EZD against NAFLD;in particular,naringenin reduces PC consumption by inhibiting the expression of PLA2G4A and thus promotes sufficient synthesis of very-low-density lipoprotein to transport excess TGs in the liver.This research provides valuable data and theoretical support for the application of EZD against NAFLD.

Comparative transcriptome and lipidome reveal that a low K^(+) signal effectively alleviates the effect induced by Ca^(2+) deficiency in cotton fibers

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.

Verbascoside exerts an anti-atherosclerotic effect by regulating liver glycerophospholipid metabolism

Verbascoside,abundant in olive mill wastewater,is a phenylethanolic glycoside with a wide range of pharmacological activities.Atherosclerosis(AS)is a common metabolic disease and abnormal lipid metabolism in liver is inseparable from its formation and development.In this study,the anti-atherosclerotic effect of verbascoside was evaluated by establishing an atherosclerosis model based on western diet feeding of apolipoprotein E-defi cient mice for 16 weeks.After 12 weeks of administration during the feeding period,the levels of total cholesterol(TC),triglyceride(TG),low density lipoprotein cholesterol(LDL-C)in the plasma of mice were signifi cantly decreased,the formation of arterial plaques was delayed,and the levels of alanine aminotransferase(ALT),aspartate aminotransferase(AST)and lactate dehydrogenase(LDH)in plasma were alleviated,showing the hepatoprotective effect.In addition,based on untargeted lipidomic analysis,verbascoside stabilized glycerophospholipid metabolism,modulated lipid metabolism disorders and reduced lipid deposition in the liver to achieve the therapeutic effi cacy against atherosclerosis by regulating cardiolipin(CL),ether-linked phosphatidylcholine(ether-PC),lysophophatidylcholine(LPC),phosphatidylcholine(PC),oxidized phosphatidylcholine(OxPC),oxidized phosphatidylethanolamine(OxPE),triacylglycerol(TG),sphingomyelin(SM)back to normal levels.

Comprehensive lipidomics and volatile compounds profiling reveals correlation of lipids and flavors in DHA-enriched egg yolk

DHA-enriched eggs have gained popularity due to their unique nutritional value,but their flavor can be challenging for some consumers to accept.The study analyzed the correlation of lipids and flavors in DHA-enriched egg yolks using comprehensive lipidomics and volatile compound analysis.The results showed that 411 lipids were detected in two egg yolk samples.Among them,148 lipid species,including 48 DHA-containing lipids,were significantly higher in DHA-enriched egg yolks than in Common ones(P<0.05).Furthermore,of the 24 volatile compounds detected,the contents of benzaldehyde,heptanal,hexanal,decanal and 2-nonanone in DHA-enriched egg yolks were significantly higher than in Common egg yolks(P<0.05).The“fishy”smell characteristic of DHAenriched egg yolks was mainly caused by volatile aldehydes,which may be produced through the hydrolysis of lipids in the egg yolk to free fatty acids and further oxidation.Analysis of the correlation network diagram revealed that phospholipids containing docosahexaenoic acid(DHA),linoleic acid,or oleic acid chains were the main contributors to the characteristic flavor of DHA-enriched egg yolks.Overall,this study explored the effect of different lipids on the flavor of DHA-enriched egg yolks and provided a theoretical basis for the production and improvement of DHA-enriched eggs.

Unraveling enhanced membrane lipid biosynthesis in Chlamydomonas reinhardtii starchless mutant sta6 by using an electrospray ionization mass spectrometry-based lipidomics method

The unicellular green alga Chlamydomonas reinhardtii,a well-established model organism,has been widely used in dissecting glycerolipid metabolism in oxygenating photosynthetic organisms.In previous studies,it has been found that shunting carbon precursors from the starch synthesis pathway can lead to a 10-fold increase in TAG content as compared to the wild type,but it is unknown whether inactivation of AGPase may affect membrane lipids biosynthesis.The study aims to investigate global changes in lipid metabolism and homeostasis in the starchless mutant C.reinhardtii sta6.By utilizing an electrospray ionization/mass spectrometry(ESI/MS)-based lipidomics approach,a total of 105 membrane lipid molecules of C.reinhardtii were resolved,including 16 monogalactosyldiacylglycerol(MGDG),16 digalactosyldiacylglycerol(DGDG),11 phosphatidylglycerol(PG),6 sulfoquinovosyldiacylglycerol(SQDG),49 diacylglyceryl-N,N,N-trimethylhomoserine(DGTS),2 phosphatidylethanolamine(PE),and 5 phosphatidylinositol(PI)molecules.The quantitative results indicated that the membrane lipid profiles were similar between the two C.reinhardtii strains grown under both low-and high-light conditions,but the cellular contents of a great number of lipids were altered in sta6 due to the defect in starch biosynthesis.Under low-light conditions,sta6 accumulated more PI,MGDG,DGDG but less amounts of DGTS as compared to WT.Under high light,sta6 cells contained higher content membrane lipids than cc-124,except for PG,which is more or less similar in both strains.Our results demonstrate that the cellular membrane lipid homeostasis underwent profound changes in the starchless mutant,and thereby its physiological impact remains to be explored.

Biomarkers and subtypes of deranged lipid metabolism in nonalcoholic fatty liver disease

Nonalcoholic fatty liver disease(NAFLD)is a heterogeneous and complex disease that is imprecisely diagnosed by liver biopsy.NAFLD covers a spectrum that ranges from simple steatosis,nonalcoholic steatohepatitis(NASH)with varying degrees of fibrosis,to cirrhosis,which is a major risk factor for hepatocellular carcinoma.Lifestyle and eating habit changes during the last century have made NAFLD the most common liver disease linked to obesity,type 2 diabetes mellitus and dyslipidemia,with a global prevalence of 25%.NAFLD arises when the uptake of fatty acids(FA)and triglycerides(TG)from circulation and de novo lipogenesis saturate the rate of FAβ-oxidation and verylow density lipoprotein(VLDL)-TG export.Deranged lipid metabolism is also associated with NAFLD progression from steatosis to NASH,and therefore,alterations in liver and serum lipidomic signatures are good indicators of the disease’s development and progression.This review focuses on the importance of the classification of NAFLD patients into different subtypes,corresponding to the main alteration(s)in the major pathways that regulate FA homeostasis leading,in each case,to the initiation and progression of NASH.This concept also supports the targeted intervention as a key approach to maximize therapeutic efficacy and opens the door to the development of precise NASH treatments.

Exercise immunology:Future directions

Several decades of research in the area of exercise immunology have shown that the immune system is highly responsive to acute and chronic exercise training.Moderate exercise bouts enhance immunosurveillance and when repeated over time mediate multiple health benefits.Most of the studies prior to 2010 relied on a few targeted outcomes related to immune function.During the past decade,technologic advances have created opportunities for a multi-omics and systems biology approach to exercise immunology.This article provides an overview of metabolomics,lipidomics,and proteomics as they pertain to exercise immunology,with a focus on immunometabolism.This review also summarizes how the composition and diversity of the gut microbiota can be influenced by exercise,with applications to human health and immunity.Exercise-induced improvements in immune function may play a critical role in countering immunosenescence and the development of chronic diseases,and emerging omics technologies will more clearly define the underlying mechanisms.This review summarizes what is currently known regarding a multi-omics approach to exercise immunology and provides future directions for investigators.

Comprehensive evaluation of the metabolic effects of insect meal from Tenebrio molitor L.in growing pigs by transcriptomics, metabolomics and lipidomics

Background:The hypothesis was tested that insect meal(IM)as protein source influences intermediary metabolism of growing pigs.To test this,30 male,5-week-old crossbred pigs were randomly assigned to 3 groups of 10 pigs each with similar body weights(BW)and fed isonitrogenous diets either without(CON)or with 5%IM(IM5)or 10%IM(IM10)from Tenebrio molitor L.for 4 weeks and key metabolic tissues(liver,muscle,plasma)were analyzed using omics-techniques.Results:Most performance parameters did not differ across the groups,whereas ileal digestibilities of most amino acids were 6.7 to 15.6%-units lower in IM10 than in CON(P<0.05).Transcriptomics of liver and skeletal muscle revealed a total of 166 and 198,respectively,transcripts differentially expressed between IM10 and CON(P<0.05).Plasma metabolomics revealed higher concentrations of alanine,citrulline,glutamate,proline,serine,tyrosine and valine and a lower concentration of asparagine in IM10 than in CON(P<0.05).Only one out of fourteen quantifiable amino acid metabolites,namely methionine sulfoxide(MetS),in plasma was elevated by 45%and 71%in IM5 and IM10,respectively,compared to CON(P<0.05).Plasma concentrations of both,major carnitine/acylcarnitine species and bile acids were not different across groups.Lipidomics of liver and plasma demonstrated no differences in the concentrations of triacylglycerols,cholesterol and the main phospholipids,lysophospholipids and sphingolipids between groups.The percentages of all individual phosphatidylcholine(PC)and phosphatidylethanolamine(PE)species in the liver showed no differences between groups,except those with 6 double bonds(PC 38:6,PC 40:6,PE 38:6,PE 40:6),which were markedly lower in IM10 than in CON(P<0.05).In line with this,the percentage of C22:6n-3 in hepatic total lipids was lower in IM10 than in the other groups(P<0.05).Conclusions:Comprehensive analyzes of the transcriptome,lipidome and metabolome of key metabolic tissues indicate that partial or complete replacement of a conventional protein source by IM in the diet has only a weak impact on the intermediary metabolism of growing pigs.Thus,it is concluded that IM from Tenebrio molitor L.can be used as a dietary source of protein in pigs without causing adverse effects on metabolism.

Lipidomics reveals carnitine palmitoyltransferase 1C protects cancer cells from lipotoxicity and senescence

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.

Advances of supercritical fluid chromatography in lipid profiling

Supercritical fluid chromatography(SFC) meets with great favor due to its high efficiency, low organic solvent consumption, and the specialty for the identification of the isomeric species. This review describes the advances of SFC in targeted and untargeted lipid profiling. The advancement of the SFC instruments and the stationary phases are summarized. Typical applications of SFC to the targeted and untargeted lipid profiling are discussed in detail. Moreover, the perspectives of SFC in the lipid profiling are also proposed. As a useful and promising tool for investigating lipids in vitro and in vivo, SFC will predictably obtain further development.

Single-cell omics analyses with single molecular detection:challenges and perspectives

The ultimate goal of single-cell analyses is to obtain the biomolecular content for each cell in unicellular and multicellular organisms at different points of their life cycle under variable environmental conditions.These require an assessment of:a)the total number of cells,b)the total number of cell types,and c)the complete and quantitative single molecular detection and identification for all classes of biopolymers,and organic and inorganic compounds,in each individual cell.For proteins,glycans,lipids,and metabolites,whose sequences cannot be amplified by copying as in the case of nucleic acids,the detection limit by mass spectrometry is about 105 molecules.Therefore,proteomic,glycomic,lipidomic,and metabolomic analyses do not yet permit the assembly of the complete single-cell omes.The construction of novel nanoelectrophoretic arrays and nano in microarrays on a single 1-cm-diameter chip has shown proof of concept for a high throughput platform for parallel processing of thousands of individual cells.Combined with dynamic secondary ion mass spectrometry,with 3D scanning capability and lateral resolution of 50 nm,the sensitivity of single molecular quantification and identification for all classes of biomolecules could be reached.Further development and routine application of such technological and instrumentation solution would allow assembly of complete omes with a quantitative assessment of structural and functional cellular diversity at the molecular level.

Lipidomics in non-alcoholic fatty liver disease

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.

Advances in paediatric nonalcoholic fatty liver disease:Role of lipidomics

Due its close relationship with obesity,nonalcoholic fatty liver disease(NAFLD)has become a major worldwide health issue even in childhood.The most accepted pathophysiological hypothesis is represented by the“multiple hits”theory,in which both hepatic intracellular lipid accumulation and insulin resistance mainly contribute to liver injury through several factors.Among these,lipotoxicity has gained particular attention.In this view,the pathogenic role of different lipid classes in NAFLD(e.g.,sphingolipids,fatty acids,ceramides,etc.)has been highlighted in recent lipidomics studies.Although there is some contrast between plasma and liver findings,lipidomic profile in the NAFLD context provides novel insights by expanding knowledge in the intricate field of NAFLD pathophysiology as well as by suggesting innovative therapeutic approaches in order to improve both NAFLD prevention and treatment strategies.Selective changes of distinct lipid species might be an attractive therapeutic target for treating NAFLD.Herein the most recent evidence in this attractive field has been summarized to provide a comprehensive overview of the lipidomic scenario in paediatric NAFLD.

LC-MS-based lipidomic analysis in distinguishing patients with nonalcoholic steatohepatitis from nonalcoholic fatty liver

Background: Nonalcoholic fatty liver disease(NAFLD) is one of the main liver diseases, and its pathologic profile includes nonalcoholic fatty liver(NAFL) and nonalcoholic steatohepatitis(NASH). However, there is no reliable non-invasive parameter in distinguishing NASH from NAFL in clinical practice. The present study was to find a non-invasive way to differentiate these two categories of NAFLD via lipidomic analysis. Methods: Lipidomic analysis was used to determine the changes of lipid moieties in blood from 20 NAFL and 10 NASH patients with liver biopsy. Liver histology was evaluated after hematoxylin and eosin staining and Masson’s trichrome staining. The profile of lipid metabolites in correlation with steatosis, inflammation, hepatocellular necroptosis, fibrosis, and NAFLD activity score(NAS) was analyzed. Results: Compared with NAFL patients, NASH patients had higher degree of steatosis, ballooning degeneration, lobular inflammation. A total of 434 different lipid molecules were identified, which were mainly composed of various phospholipids and triacylglycerols. Many lipids, such as phosphatidylcholine(PC)(P-22:0/18:1), sphingomyelin(SM)(d14:0/18:0), SM(d14:0/24:0), SM(d14:0/22:0), phosphatidylethanolamine(PE)(18:0/22:5), PC(O-22:2/12:0), and PC(26:1/11:0) were elevated in the NASH group compared to those in the NAFL group. Specific analysis revealed an overall lipidomic profile shift from NAFL to NASH, and identified valuable lipid moieties, such as PCs [PC(14:0/18:2), PE(18:0/22:5) and PC(26:1/11:0)] or plasmalogens [PC(O-22:0/0:0), PC(O-18:0/0:0), PC(O-16:0/0:0)], which were significantly altered in NASH patients. In addition, PC(14:0/18:2), phosphatidic acid(18:2/24:4) were positively correlated with NAS;whereas PC(18:0/0:0) was correlated positively with fibrosis score. Conclusions: The present study revealed overall lipidomic profile shift from NAFL to NASH, identified valuable lipid moieties which may be non-invasive biomarkers in the categorization of NAFLD. The correlations between lipid moieties and NAS and fibrosis scores indicate that these lipid biomarkers may be used to predict the severity of the disease.

Perspectives on diacylglycerol-induced improvement of insulin sensitivity in type 2 diabetes

Diacylglycerol(DAG)-based edible oils have attracted increasing research interest owing to their healthpromoting properties.Recent animal and human studies showed that an increased 1,2-DAG content in the liver and skeletal muscle may cause insulin resistance.However,earlier studies using animal models or humans reported that dietary DAGs with a 1,2-DAGs to 1,3-D AGs ratio of approximately 3:7 could improve insulin sensitivity in type 2 diabetic patients.This conflict raises the question of whether there is a link between the ingested DAGs and endogenous DAGs during their metabolism.To make a contribution to this field,this review provides an overview of the metabolic pathways of ingested DAGs and biological roles of DAGs(ingested and endogenous)in the change of insulin sensitivity.Accordingly,strategies for further investigations on the metabolism of DAGs are proposed.