There is growing evidence that metabolic alterations play an important role in cancer development and progression.The metabolism of cancer cells is reprogrammed in order to support their rapid proliferation.Elevated f...There is growing evidence that metabolic alterations play an important role in cancer development and progression.The metabolism of cancer cells is reprogrammed in order to support their rapid proliferation.Elevated fatty acid synthesis is one of the most important aberrations of cancer cell metabolism.An enhancement of fatty acids synthesis is required both for carcinogenesis and cancer cell survival,as inhibition of key lipogenic enzymes slows down the growth of tumor cells and impairs their survival.Based on the data that serum fatty acid synthase(FASN),also known as oncoantigen 519,is elevated in patients with certain types of cancer,its serum level was proposed as a marker of neoplasia.This review aims to demonstrate the changes in lipid metabolism and other metabolic processes associated with lipid metabolism in pancreatic ductal adenocarcinoma(PDAC),the most common pancreatic neoplasm,characterized by high mortality.We also addressed the influence of some oncogenic factors and tumor suppressors on pancreatic cancer cell metabolism.Additionally the review discusses the potential role of elevated lipid synthesis in diagnosis and treatment of pancreatic cancer.In particular,FASN is a viable candidate for indicator of pathologic state,marker of neoplasia,as well as,pharmacological treatment target in pancreatic cancer.Recent research showed that,in addition to lipogenesis,certain cancer cells can use fatty acids from circulation,derived from diet(chylomicrons),synthesized in liver,or released from adipose tissue for their growth.Thus,the interactions between de novo lipogenesis and uptake of fatty acids from circulation by PDAC cells require further investigation.展开更多
Vascular etiology is the second most prevalent cause of cognitive impairment globally.Endothelin-1,which is produced and secreted by endothelial cells and astrocytes,is implicated in the pathogenesis of stroke.However...Vascular etiology is the second most prevalent cause of cognitive impairment globally.Endothelin-1,which is produced and secreted by endothelial cells and astrocytes,is implicated in the pathogenesis of stroke.However,the way in which changes in astrocytic endothelin-1 lead to poststroke cognitive deficits following transient middle cerebral artery occlusion is not well understood.Here,using mice in which astrocytic endothelin-1 was overexpressed,we found that the selective overexpression of endothelin-1 by astrocytic cells led to ischemic stroke-related dementia(1 hour of ischemia;7 days,28 days,or 3 months of reperfusion).We also revealed that astrocytic endothelin-1 overexpression contributed to the role of neural stem cell proliferation but impaired neurogenesis in the dentate gyrus of the hippocampus after middle cerebral artery occlusion.Comprehensive proteome profiles and western blot analysis confirmed that levels of glial fibrillary acidic protein and peroxiredoxin 6,which were differentially expressed in the brain,were significantly increased in mice with astrocytic endothelin-1 overexpression in comparison with wild-type mice 28 days after ischemic stroke.Moreover,the levels of the enriched differentially expressed proteins were closely related to lipid metabolism,as indicated by Kyoto Encyclopedia of Genes and Genomes pathway analysis.Liquid chromatography-mass spectrometry nontargeted metabolite profiling of brain tissues showed that astrocytic endothelin-1 overexpression altered lipid metabolism products such as glycerol phosphatidylcholine,sphingomyelin,and phosphatidic acid.Overall,this study demonstrates that astrocytic endothelin-1 overexpression can impair hippocampal neurogenesis and that it is correlated with lipid metabolism in poststroke cognitive dysfunction.展开更多
Lipid metabolism refers to the biochemical processes involved in synthesising,storing,utilising,and breaking down lipids in living organisms.Lipids are essential for various physiological functions,including energy st...Lipid metabolism refers to the biochemical processes involved in synthesising,storing,utilising,and breaking down lipids in living organisms.Lipids are essential for various physiological functions,including energy storage,insulation,protection of organs,and the formation of cell membranes.Aberrations in lipid metabolism can lead to a number of health issues,such as atherosclerosis,obesity,and type 2 diabetes,etc.[1].Environmental factors,genetics,and lifestyle factors are some of the factors that can contribute to the development of dyslipidemia.Currently,there is a growing academic interest in the impact of environmental factors.展开更多
BACKGROUND Hepatocellular carcinoma(HCC)is one of the most common types of tumors.The influence of lipid metabolism disruption on the development of HCC has been demonstrated in published studies.AIM To establish an H...BACKGROUND Hepatocellular carcinoma(HCC)is one of the most common types of tumors.The influence of lipid metabolism disruption on the development of HCC has been demonstrated in published studies.AIM To establish an HCC prognostic model for lipid metabolism-related long non-coding RNAs(LMR-lncRNAs)and conduct in-depth research on the specific role of novel LMR-lncRNAs in HCC.METHODS Correlation and differential expression analyses of The Cancer Genome Atlas data were used to identify differentially expressed LMR-lncRNAs.Quantitative real-time polymerase chain reaction analysis was used to evaluate the expression of LMR-lncRNAs.Nile red staining was employed to observe intracellular lipid levels.The interaction between RP11-817I4.1,miR-3120-3p,and ATP citrate lyase(ACLY)was validated through the performance of dual-luciferase reporter gene and RIP assays.RESULTS Three LMR-lncRNAs(negative regulator of antiviral response,RNA transmembrane and coiled-coil domain family 1 antisense RNA 1,and RP11-817I4.1)were identified as predictive markers for HCC patients and were utilized in the construction of risk models.Additionally,proliferation,migration,and invasion were reduced by RP11-817I4.1 knockdown.An increase in lipid levels in HCC cells was significantly induced by RP11-817I4.1 through the miR-3120-3p/ACLY axis.CONCLUSION LMR-lncRNAs have the capacity to predict the clinical characteristics and prognoses of HCC patients,and the discovery of a novel LMR-lncRNAs,RP11-817I4.1,revealed its role in promoting lipid accumulation,thereby accelerating the onset and progression of HCC.展开更多
The aquaculture industry has developed significantly over the past few decades and has had a substantial impact on the global food supply and marine fisheries resources.However,some problems arise behind the scenes du...The aquaculture industry has developed significantly over the past few decades and has had a substantial impact on the global food supply and marine fisheries resources.However,some problems arise behind the scenes due to excessive intensive farming,such as slow animal growth,frequent disease,and lipid metabolism disorders.These problems have limited the sustainable development of the aquaculture industry,and a continuable solution is required.The use of fungal polysaccharide appears to provide a solution to these problems.Therefore,different supplemented levels of Poria cocos polysaccharide(PCP)(0,0.4,0.8,1.2,1.6,and 2.0 g/kg,respectively)were fed to spotted sea bass(Lateolabrax maculatus)in similar size(30.28±0.18 g)in current study.The effects of PCP on growth,physiological parameters,and lipid metabolism of spotted sea bass were investigated after a 4-week rearing period.Results showed,fish with PCP intake presented a significantly higher weight gain,specific growth rate,and a significantly lower feed conversion ratio.Significantly higher trypsin activity in liver and intestine were observed in fish with PCP intake.The superoxide dismutase activity in serum and liver of fish with PCP intake were significantly improved,while significantly higher serum total antioxidant capacity and hepatic catalase activity were also observed.However,no significant differences in lysozyme and alkaline phosphatase activity were evident among groups.Fish with PCP intake showed a significantly lower total cholesterol,but no noteworthy change in triglyceride and lipid-metabolismrelated genes expression were observed among groups.Results indicated that intake of PCP has a positive effect on growth and antioxidant capacity of spotted sea bass,but seems to have a limited effect on the non-specific immunity and lipid metabolism of spotted sea bass.Based on the regression analysis results,1.4 g/kg of PCP is the optimal dose for spotted sea bass in size(30.28±0.18 g).展开更多
Esophageal cancer is an upper gastrointestinal malignancy with a bleak prognosis.It is still being explored in depth due to its complex molecular mechanisms of occurrence and development.Lipids play a crucial role in ...Esophageal cancer is an upper gastrointestinal malignancy with a bleak prognosis.It is still being explored in depth due to its complex molecular mechanisms of occurrence and development.Lipids play a crucial role in cells by participating in energy supply,biofilm formation,and signal transduction processes,and lipid metabolic reprogramming also constitutes a significant characteristic of malignant tumors.More and more studies have found esophageal cancer has obvious lipid metabolism abnormalities throughout its beginning,progress,and treatment resistance.The inhibition of tumor growth and the enhancement of antitumor therapy efficacy can be achieved through the regulation of lipid metabolism.Therefore,we reviewed and analyzed the research results and latest findings for lipid metabolism and associated analysis techniques in esophageal cancer,and comprehensively proved the value of lipid metabolic reprogramming in the evolution and treatment resistance of esophageal cancer,as well as its significance in exploring potential therapeutic targets and biomarkers.展开更多
To determine the effects of plant-based meat analogues on the metabolic health and the possible mechanisms,mice were fed with a real pork diet(AP),a real beef diet(AB),a plant-based pork analogue diet(PP)and plant-bas...To determine the effects of plant-based meat analogues on the metabolic health and the possible mechanisms,mice were fed with a real pork diet(AP),a real beef diet(AB),a plant-based pork analogue diet(PP)and plant-based beef analogue diet(PB)for 68 days.Compared with real meat,the plant-based meat analogues increased food and energy intake,body weight,white fat and liver weight and caused adipocyte hypertrophy,hepatic lipid droplet accumulation,and inflammatory responses in mice.Metabolomics revealed that plantbased meat analogues altered the composition of serum metabolites,which regulated lipid metabolism homeostasis.The PB diet upregulated gene expression related to lipid synthesis,lipolysis and adipocyte differentiation while the PP diet upregulated expression of lipolysis-related genes but downregulated expression of adipocyte differentiation-related genes in white adipose tissue.Meanwhile,both PP and PB diets upregulated lipid influx-and synthesis-related genes but downregulated lipid oxidation-related genes in liver.The specific metabolite biomarkers may affect fat accumulation mainly by direct lipid metabolism pathways or indirect amino acid metabolism,protein digestion and absorption,bile secretion,aminoacyl-tRNA biosynthesis,neuroactive ligand-receptor interaction and ABC transporters pathways.These findings provide a new insight into understanding the differences in nutritional functions of meat and plant-based meat analogues.展开更多
Lactobacillus are considered promising therapeutic methods for nonalcoholic fatty liver disease(NAFLD).The effects of two strains of Ltmosilactobacillus mucosae on NAFLD were investigated in this study.Fourweek-old ma...Lactobacillus are considered promising therapeutic methods for nonalcoholic fatty liver disease(NAFLD).The effects of two strains of Ltmosilactobacillus mucosae on NAFLD were investigated in this study.Fourweek-old male C57BL/6J mice were divided into 4 groups(n=8 per group,Control,Model,FZJTZ26M3,FGSYC17L3).L.mucosae FZJTZ26M3 reduced the mice 's body weight,liver weight,and adipose tissue weight after 12 weeks of therapy.According to serum analysis,total cholesterol,triacylglycerol,and low-density lipoprotein cholesterol significantly decreased after L.mucosae FZJTZ26M3 intervention.Liver pathology showed that L.mucosae FZJTZ26M3 was effective to ameliorate lipid deposition in NAFLD mice.Additionally,the expression of the gene related to lipid metabolism in the liver and adipose tissue was analyzed,and the results indicated that L.mucosae FZJTZ26M3 could alleviate NAFLD by regulating lipid metabolism.Furthermore,the results of 16S rRNA gene sequencing revealed a drop in the relative abundance of Ruminococcaceae,which is linked to inflammation,but the relative abundance of a potential probiotic Akkermansia significantly increased after L.mucosae FZJTZ26M3 intervention.Generally,L.mucosae FZJTZ26M3 could be a candidate to prevent NAFLD.展开更多
Background:In this study,we used network pharmacology and molecular docking combined with vitro experiments to explore the potential mechanism of action of Gualou Qumai pill(GLQMP)against DKD.Methods:We screened effec...Background:In this study,we used network pharmacology and molecular docking combined with vitro experiments to explore the potential mechanism of action of Gualou Qumai pill(GLQMP)against DKD.Methods:We screened effective compounds and drug targets using Chinese medicine systemic pharmacology database and analysis platform and Chinese medicine molecular mechanism bioinformatics analysis tools;and searched for DKD targets using human online Mendelian genetics and gene cards.The potential targets of GLQMP for DKD were obtained through the intersection of drug targets and disease targets.Cytoscape software was applied to build herbal medicine-active compound-target-disease networks and analyze them;protein-protein interaction networks were analyzed using the STRING database platform;gene ontology and Kyoto Encyclopedia of Genes and Genomes were used for gene ontology and gene and genome encyclopedia to enrich potential targets using the DAVID database;and the AutoDock Vina 1.1.2 software for molecular docking of key targets with corresponding key components.In vitro experiments were validated by CCK8,oil red O staining,TC,TG,RT-qPCR,and Western blot.Results:Through network pharmacology analysis,a total of 99 potential therapeutic targets of GLQMP for DKD and the corresponding 38 active compounds were obtained,and 5 core compounds were identified.By constructing the protein-protein interaction network and performing network topology analysis,we found that PPARA and PPARG were the key targets,and then we molecularly docked these two key targets with the 38 active compounds,especially the 5 core compounds,and found that PPARA and PPARG had good binding ability with a variety of compounds.In vitro experiments showed that GLQMP was able to ameliorate HK-2 cell injury under high glucose stress,improve cell viability,reduce TC and TG levels as well as decrease the accumulation of lipid droplets,and RT-qPCR and Western blot confirmed that GLQMP was able to promote the expression levels of PPARA and PPARG.Conclusion:Overall,this study revealed the active compounds,important targets and possible mechanisms of GLQMP treatment for DKD,and conducted preliminary verification experiments on its correctness,provided novel insights into the treatment of DKD by GLQMP.展开更多
Currently, accumulating pieces of evidence indicate that probiotics, living in the gastrointestinal tract, play an important role in regulating host metabolism. As a tool, probiotics have great potential for treating ...Currently, accumulating pieces of evidence indicate that probiotics, living in the gastrointestinal tract, play an important role in regulating host metabolism. As a tool, probiotics have great potential for treating lipid metabolism diseases. However, the relationship between probiotics and abnormal lipid metabolism is still unclear, and the mechanism of action has been become a focus of microbiome research. Therefore, taking intestinal probiotics as the starting point, this article combs the relationship between probiotics and lipid metabolism. Moreover, we discuss the underlying mechanisms of intestinal probiotics regulating lipid metabolism and summarize the therapeutic strategies for abnormal lipids metabolism. This article provides a reference for the further utilization of probiotics in the field of functional foods(food industry). Meanwhile, it will benefit the clinical diagnosis and treatment of lipid metabolism diseases.展开更多
Tumorigenesis involves metabolic reprogramming and abnormal lipid metabolism,which is manifested by increased endogenous fat mobilization,hypertriglyceridemia,and increased fatty acid synthesis.Fatty acid synthase(FAS...Tumorigenesis involves metabolic reprogramming and abnormal lipid metabolism,which is manifested by increased endogenous fat mobilization,hypertriglyceridemia,and increased fatty acid synthesis.Fatty acid synthase(FASN)is a key enzyme for the de novo synthesis of fatty acids,and monoacylglycerol esterase(MGLL)is an important metabolic enzyme that converts triglycerides into free fatty acids.Both enzymes play an important role in lipid metabolism and are associated with tumor-related signaling pathways,the most common of which is the PI3K–AKT signaling pathway.They can also regulate the immune microenvironment,participate in epithelial–mesenchymal transition,and then regulate tumor invasion and metastasis.Current literature have shown that these two genes are abnormally expressed in many types of tumors and are highly correlated with tumor migration and invasion.This article introduces the structures and functions of FASN and MGLL,their relationship with abnormal lipid metabolism,and the mechanism of the regulation of tumor invasion and metastasis and reviews the research progress of the relationship of FASN and MGLL with tumor invasion and metastasis.展开更多
Background Lipid metabolism differs significantly between grazing and stall-feeding lambs,affecting the quality of livestock products.As two critical organs of lipid metabolism,the differences between feeding patterns...Background Lipid metabolism differs significantly between grazing and stall-feeding lambs,affecting the quality of livestock products.As two critical organs of lipid metabolism,the differences between feeding patterns on rumen and liver metabolism remain unclear.In this study,16S rRNA,metagenomics,transcriptomics,and untargeted metabolomics were utilized to investigate the key rumen microorganisms and metabolites,as well as liver genes and metabolites associated with fatty acid metabolism under indoor feeding(F)and grazing(G).Results Compared with grazing,indoor feeding increased ruminal propionate content.Using metagenome sequencing in combination with 16S rRNA amplicon sequencing,the results showed that the abundance of propionate-producing Succiniclasticum and hydrogenating bacteria Tenericutes was enriched in the F group.For rumen metabolism,grazing caused up-regulation of EPA,DHA and oleic acid and down-regulation of decanoic acid,as well as,screening for 2-ketobutyric acid as a vital differential metabolite,which was enriched in the propionate metabolism pathway.In the liver,indoor feeding increased 3-hydroxypropanoate and citric acid content,causing changes in propionate metabolism and citrate cycle,while decreasing the ETA content.Then,the liver transcriptome revealed that 11 lipid-related genes were differentially expressed in the two feeding patterns.Correlation analysis showed that the expression of CYP4A6,FADS1,FADS2,ALDH6A1 and CYP2C23 was significantly associated with the propionate metabolism process,suggesting that propionate metabolism may be an important factor mediating the hepatic lipid metabolism.Besides,the unsaturated fatty acids in muscle,rumen and liver also had a close correlation.Conclusions Overall,our data demonstrated that rumen microbial-driven metabolite from grazing lambs potentially regulates multiple hepatic lipid-related genes,ultimately affecting body fatty acid metabolism.展开更多
Objective:To investigate the proteomic characteristics of overweight/obesity and related abnormal glucose and lipid metabolism caused by phlegm-dampness retention to identify related biomarkers.Methods:Seventy-one sub...Objective:To investigate the proteomic characteristics of overweight/obesity and related abnormal glucose and lipid metabolism caused by phlegm-dampness retention to identify related biomarkers.Methods:Seventy-one subjects were enrolled in the study.We assessed blood glucose,blood lipids,body mass index(BMI),and phlegm-dampness pattern,which was confirmed by a traditional Chinese medicine clinician.Of the participants,we included healthy participants with normal weight(NW,n=23),overweight/obese participants with normal metabolism(ONM,n=19),overweight/obese participants with pre-diabetes(OPD,n=12),and overweight/obese participants with marginally-elevated blood lipids(OML,n=17).Among them,the ONM,OPD,and OML groups were diagnosed with phlegmdampness pattern.The data-independent acquisition(DIA)method was first used to analyze the plasma protein expression of each group,and the relevant differential proteins of each group were screened.The co-expressed proteins were evaluated by Venn analysis.The pathway analyses of the differential proteins were analyzed using Ingenuity Pathway Analysis(IPA)software.Parallel reaction monitoring(PRM)was used to verify the differential and common proteins in each group.Results:After comparing ONM,OPD,and OML groups with NW group,we identified the differentially expressed proteins(DEPs).Next,we determined the DEPs among OPD,OML,and ONM groups.Using Venn analysis of the DEPs in each group,24 co-expressed proteins were screened.Two co-expressed proteins were verified by PRM.IPA analysis showed that pathways including LXR/RXR activation,acute phase response signaling,and FXR/RXR activation were common to all three groups of phlegmdamp overweight/obesity participants.However,the activation or inhibition of these pathways was different among the three groups.Conclusion:Participants with overweight/obesity have similar proteomic characteristics,though each type shows specific proteomic characteristics.Two co-expressed proteins,VTN and ORM1,are potential biomarkers for glucose and lipid metabolism diseases with overweight/obesity caused by phlegmdampness retention.展开更多
Night lighting has been shown to affect wild animals.To date,the effects of night lighting on the metabolic homeostasis of birds that spend short time in urban environments remain unclear.Using model bird species Zebr...Night lighting has been shown to affect wild animals.To date,the effects of night lighting on the metabolic homeostasis of birds that spend short time in urban environments remain unclear.Using model bird species Zebra Finch(Taeniopygia guttata),we investigated the effects of short-term night lighting on liver transcriptome,blood glucose,triglyceride,and thyroxine(T4 and T3)levels in birds exposed to two different night lighting duration periods(three days and six days).After three days of night lighting exposure,the expression of genes involved in fat synthesis in the liver was upregulated while the expression of genes involved in fatty acid oxidation and triglyceride decomposition was downregulated.There was also a reduction in blood triglyceride,glucose,and T3 concentrations.However,after six days of night lighting,the expression of genes associated with fatty acid decomposition and hyperglycemia in the liver was upregulated,while the expression of genes involved in fat synthesis was downregulated.Simultaneously,blood glucose levels and T3 concentration increased.These findings indicate that short-term exposure to night lighting can disrupt the lipid and glucose metabolism of small passerine birds,and longer stopovers in urban area with intense night lighting may cause birds to consume more lipid energy.展开更多
Forty-eight male Lezhi black goat kids with similar body weight((12.09±1.70)kg)and age((60±5)d)were used to determine the effect of dietary copper(Cu),in the form of reagent grade Cu sulfate(CuSO4∙5H2O),on p...Forty-eight male Lezhi black goat kids with similar body weight((12.09±1.70)kg)and age((60±5)d)were used to determine the effect of dietary copper(Cu),in the form of reagent grade Cu sulfate(CuSO4∙5H2O),on performance,serum lipid profile,and the relative mRNA abundance of genes involved in lipid metabolism.Goat kids were stratified by body weight and randomly assigned to one of 4 treatment groups.Each treatment consisted of 12 replicate pens with each pen containing one goat kid.Treatment groups received the basal diet with no supplemental Cu(control),basal diet plus 10 mg of Cu kg^(-1)of dry matter(DM),basal diet plus 20 mg of Cu kg^(-1)of DM,or basal diet plus 30 mg of Cu kg^(-1)of DM.Goats were housed individually in pens and fed a high-concentrate pelleted diet for 60 d.Average daily gain,average daily feed intake and feed:gain of goats were not affected by dietary Cu supplementation(P>0.10).No differences were detected in serum total cholesterol,triglyceride,and high density lipoprotein cholesterol concentrations of goat kids fed with different Cu concentrations(P>0.05).However,serum low density lipoprotein cholesterol concentrations decreased linearly(P=0.01)as the concentration of dietary Cu increased.Intramuscular fat content of longissimus muscle increased(P=0.002)quadratically and liver Cu concentrations increased(P<0.001)linearly as dietary Cu concentration increased.Compared with the control,dietary supplementation of 20 mg Cu kg^(-1)DM decreased the relative mRNA abundance of fatty acid-binding protein 4(P=0.01)and lipoprotein lipase(P=0.05),and tended to decrease the relative mRNA abundance of carnitine palmitoyltransferase I(P=0.06)in longissimus muscle of goats.The relative mRNA abundance of peroxisome proliferator-activated receptor alpha(P<0.001),carnitine acetyltransferase(P=0.001),and carnitine palmitoyltransferase Ⅰ(P=0.001)were also decreased in liver by Cu supplementation.These results indicate that dietary supplementation of Cu modified lipid metabolism by increasing muscular fat and decreasing serum low density lipoprotein cholesterol,and the modification might be associated with the reduction of relative mRNA abundance of genes for oxidation of long-chain fatty acid in muscle and liver of Lezhi black goat kids.展开更多
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 ...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.展开更多
Background Intrauterine growth restriction(IUGR)can cause lipid disorders in infants and have long-term adverse effects on their growth and development.Clostridium butyricum(C.butyricum),a kind of emerging probiotics,...Background Intrauterine growth restriction(IUGR)can cause lipid disorders in infants and have long-term adverse effects on their growth and development.Clostridium butyricum(C.butyricum),a kind of emerging probiotics,has been reported to effectively attenuate lipid metabolism dysfunctions.Therefore,the objective of this study was to investigate the effects of C.butyricum supplementation on hepatic lipid disorders in IUGR suckling piglets.Methods Sixteen IUGR and eight normal birth weight(NBW)neonatal male piglets were used in this study.From d 3to d 24,in addition to drinking milk,the eight NBW piglets(NBW-CON group,n=8)and eight IUGR piglets(IUGR-CON group,n=8)were given 10 mL sterile saline once a day,while the remaining IUGR piglets(IUGR-CB group,n=8)were orally administered C.butyricum at a dose of 2×108colony-forming units(CFU)/kg body weight(suspended in 10 mL sterile saline)at the same frequency.Results The IUGR-CON piglets exhibited restricted growth,impaired hepatic morphology,disordered lipid metabolism,increased abundance of opportunistic pathogens and altered ileum and liver bile acid(BA)profiles.However,C.butyricum supplementation reshaped the gut microbiota of the IUGR-CB piglets,characterized by a decreased abundance of opportunistic pathogens in the ileum,including Streptococcus and Enterococcus.The decrease in these bile salt hydrolase(BSH)-producing microbes increased the content of conjugated BAs,which could be transported to the liver and function as signaling molecules to activate liver X receptorα(LXRα)and farnesoid X receptor(FXR).This activation effectively accelerated the synthesis and oxidation of fatty acids and down-regulated the total cholesterol level by decreasing the synthesis and promoting the efflux of cholesterol.As a result,the growth performance and morphological structure of the liver improved in the IUGR piglets.Conclusion These results indicate that C.butyricum supplementation in IUGR suckling piglets could decrease the abundance of BSH-producing microbes(Streptococcus and Enterococcus).This decrease altered the ileum and liver BA profiles and consequently activated the expression of hepatic LXRαand FXR.The activation of these two signaling molecules could effectively normalize the lipid metabolism and improve the growth performance of IUGR suckling piglets.展开更多
Background:Methionine or lysine has been reported to influence DNA methylation and fat metabolism,but their combined effects in N6-methyl-adenosine(m^(6)A)RNA methylation remain unclarified.The combined effects of rum...Background:Methionine or lysine has been reported to influence DNA methylation and fat metabolism,but their combined effects in N6-methyl-adenosine(m^(6)A)RNA methylation remain unclarified.The combined effects of rumen-protected methionine and lysine(RML)in a low-protein(LP)diet on lipid metabolism,m^(6)A RNA methylation,and fatty acid(FA)profiles in the liver and muscle of lambs were investigated.Sixty-three male lambs were divided into three treatment groups,three pens per group and seven lambs per pen.The lambs were fed a 14.5%crude protein(CP)diet(adequate protein[NP]),12.5%CP diet(LP),and a LP diet plus RML(LP+RML)for 60 d.Results:The results showed that the addition of RML in a LP diet tended to lower the concentrations of plasma leptin(P=0.07),triglyceride(P=0.05),and non-esterified FA(P=0.08).Feeding a LP diet increased the enzyme activity or m RNA expression of lipogenic enzymes and decreased lipolytic enzymes compared with the NP diet.This effect was reversed by supplementation of RML with a LP diet.The inclusion of RML in a LP diet affected the polyunsaturated fatty acids(PUFA),n-3 PUFA,and n-6 PUFA in the liver but not in the muscle,which might be linked with altered expression of FA desaturase-1(FADS1)and acetyl-Co A carboxylase(ACC).A LP diet supplemented with RML increased(P<0.05)total m^(6)A levels in the liver and muscle and were accompanied by decreased expression of fat mass and obesity-associated protein(FTO)and alk B homologue 5(ALKBH5).The m RNA expressions of methyltransferase-like 3(METTL3)and methyltransferase-like 14(METTL14)in the LP+RML diet group were lower than those in the other two groups.Supplementation of RML with a LP diet affected only liver YTH domain family(YTHDF2)proteins(P<0.05)and muscle YTHDF3(P=0.09),which can be explained by limited m^(6)Abinding proteins that were mediated in m RNA fate.Conclusions:Our findings showed that the inclusion of RML in a LP diet could alter fat deposition through modulations of lipogenesis and lipolysis in the liver and muscle.These changes in fat metabolism may be associated with the modification of m^(6)A RNA methylation.展开更多
Scope: Circadian disorder and high-fat diet(HFD)can disturb lipid metabolism homeostasis and may promote the development of various metabolic diseases. The relationship between them is of great concern. This study aim...Scope: Circadian disorder and high-fat diet(HFD)can disturb lipid metabolism homeostasis and may promote the development of various metabolic diseases. The relationship between them is of great concern. This study aimed to explore the effects of Per1/Per2 double knockout(DKO)on hepatic lipid metabolism in mice under HFD and HFD with docosahexaenoic acid(DHA)substitution. Methods and results: Both wild type(WT)and DKO male C57BL/6 mice were fed with normal chow diet(CON), HFD, or HFD with DHA substitution(AO)for 15 weeks. At the end of the experiment, mice were sacrificed at zeitgeber time(ZT)0(7:00 am)or ZT12(7:00 pm). Pathological indicators were determined using histological and biochemical methods. Hepatic transcriptome sequencing analysis showed that DKO mice exhibited multiple dysfunctions in diurnal rhythm, drug metabolism, cell cycle, cancer pathways, and lipid metabolism. HFD had greater effects on fatty acid oxidation and cholesterol synthesis and metabolism in Per1-/-Per2-/-mice, which was improved by DHA substitution. Conclusions: Per1/Per2 played an important role in the circadian regulation of hepatic lipid metabolism, and DKO mice were more sensitive to HFD. DHA can improve circadian-related lipid metabolism disruption induced by HFD in mice.展开更多
基金Supported by Medical University of Gdansk Grants ST-41,ST-40
文摘There is growing evidence that metabolic alterations play an important role in cancer development and progression.The metabolism of cancer cells is reprogrammed in order to support their rapid proliferation.Elevated fatty acid synthesis is one of the most important aberrations of cancer cell metabolism.An enhancement of fatty acids synthesis is required both for carcinogenesis and cancer cell survival,as inhibition of key lipogenic enzymes slows down the growth of tumor cells and impairs their survival.Based on the data that serum fatty acid synthase(FASN),also known as oncoantigen 519,is elevated in patients with certain types of cancer,its serum level was proposed as a marker of neoplasia.This review aims to demonstrate the changes in lipid metabolism and other metabolic processes associated with lipid metabolism in pancreatic ductal adenocarcinoma(PDAC),the most common pancreatic neoplasm,characterized by high mortality.We also addressed the influence of some oncogenic factors and tumor suppressors on pancreatic cancer cell metabolism.Additionally the review discusses the potential role of elevated lipid synthesis in diagnosis and treatment of pancreatic cancer.In particular,FASN is a viable candidate for indicator of pathologic state,marker of neoplasia,as well as,pharmacological treatment target in pancreatic cancer.Recent research showed that,in addition to lipogenesis,certain cancer cells can use fatty acids from circulation,derived from diet(chylomicrons),synthesized in liver,or released from adipose tissue for their growth.Thus,the interactions between de novo lipogenesis and uptake of fatty acids from circulation by PDAC cells require further investigation.
基金financially supported by the National Natural Science Foundation of China,No.81303115,81774042 (both to XC)the Pearl River S&T Nova Program of Guangzhou,No.201806010025 (to XC)+3 种基金the Specialty Program of Guangdong Province Hospital of Chinese Medicine of China,No.YN2018ZD07 (to XC)the Natural Science Foundatior of Guangdong Province of China,No.2023A1515012174 (to JL)the Science and Technology Program of Guangzhou of China,No.20210201 0268 (to XC),20210201 0339 (to JS)Guangdong Provincial Key Laboratory of Research on Emergency in TCM,Nos.2018-75,2019-140 (to JS)
文摘Vascular etiology is the second most prevalent cause of cognitive impairment globally.Endothelin-1,which is produced and secreted by endothelial cells and astrocytes,is implicated in the pathogenesis of stroke.However,the way in which changes in astrocytic endothelin-1 lead to poststroke cognitive deficits following transient middle cerebral artery occlusion is not well understood.Here,using mice in which astrocytic endothelin-1 was overexpressed,we found that the selective overexpression of endothelin-1 by astrocytic cells led to ischemic stroke-related dementia(1 hour of ischemia;7 days,28 days,or 3 months of reperfusion).We also revealed that astrocytic endothelin-1 overexpression contributed to the role of neural stem cell proliferation but impaired neurogenesis in the dentate gyrus of the hippocampus after middle cerebral artery occlusion.Comprehensive proteome profiles and western blot analysis confirmed that levels of glial fibrillary acidic protein and peroxiredoxin 6,which were differentially expressed in the brain,were significantly increased in mice with astrocytic endothelin-1 overexpression in comparison with wild-type mice 28 days after ischemic stroke.Moreover,the levels of the enriched differentially expressed proteins were closely related to lipid metabolism,as indicated by Kyoto Encyclopedia of Genes and Genomes pathway analysis.Liquid chromatography-mass spectrometry nontargeted metabolite profiling of brain tissues showed that astrocytic endothelin-1 overexpression altered lipid metabolism products such as glycerol phosphatidylcholine,sphingomyelin,and phosphatidic acid.Overall,this study demonstrates that astrocytic endothelin-1 overexpression can impair hippocampal neurogenesis and that it is correlated with lipid metabolism in poststroke cognitive dysfunction.
基金supported by the Natural Science Foundation of Heilongjiang Province[LH2021H011].
文摘Lipid metabolism refers to the biochemical processes involved in synthesising,storing,utilising,and breaking down lipids in living organisms.Lipids are essential for various physiological functions,including energy storage,insulation,protection of organs,and the formation of cell membranes.Aberrations in lipid metabolism can lead to a number of health issues,such as atherosclerosis,obesity,and type 2 diabetes,etc.[1].Environmental factors,genetics,and lifestyle factors are some of the factors that can contribute to the development of dyslipidemia.Currently,there is a growing academic interest in the impact of environmental factors.
基金National Natural Science Foundation of China,No.81460132Yunnan Pacific Department of Science,Technology-Kunming Medical University Applied Basic Research Joint Special Fund Project,No.2018FE001(-224).
文摘BACKGROUND Hepatocellular carcinoma(HCC)is one of the most common types of tumors.The influence of lipid metabolism disruption on the development of HCC has been demonstrated in published studies.AIM To establish an HCC prognostic model for lipid metabolism-related long non-coding RNAs(LMR-lncRNAs)and conduct in-depth research on the specific role of novel LMR-lncRNAs in HCC.METHODS Correlation and differential expression analyses of The Cancer Genome Atlas data were used to identify differentially expressed LMR-lncRNAs.Quantitative real-time polymerase chain reaction analysis was used to evaluate the expression of LMR-lncRNAs.Nile red staining was employed to observe intracellular lipid levels.The interaction between RP11-817I4.1,miR-3120-3p,and ATP citrate lyase(ACLY)was validated through the performance of dual-luciferase reporter gene and RIP assays.RESULTS Three LMR-lncRNAs(negative regulator of antiviral response,RNA transmembrane and coiled-coil domain family 1 antisense RNA 1,and RP11-817I4.1)were identified as predictive markers for HCC patients and were utilized in the construction of risk models.Additionally,proliferation,migration,and invasion were reduced by RP11-817I4.1 knockdown.An increase in lipid levels in HCC cells was significantly induced by RP11-817I4.1 through the miR-3120-3p/ACLY axis.CONCLUSION LMR-lncRNAs have the capacity to predict the clinical characteristics and prognoses of HCC patients,and the discovery of a novel LMR-lncRNAs,RP11-817I4.1,revealed its role in promoting lipid accumulation,thereby accelerating the onset and progression of HCC.
基金the Science and Technology Planning Project in FujianChina(No.2015N0010)+1 种基金the Science and Technology Planning Project in XiamenChina(No.3502Z20143017)。
文摘The aquaculture industry has developed significantly over the past few decades and has had a substantial impact on the global food supply and marine fisheries resources.However,some problems arise behind the scenes due to excessive intensive farming,such as slow animal growth,frequent disease,and lipid metabolism disorders.These problems have limited the sustainable development of the aquaculture industry,and a continuable solution is required.The use of fungal polysaccharide appears to provide a solution to these problems.Therefore,different supplemented levels of Poria cocos polysaccharide(PCP)(0,0.4,0.8,1.2,1.6,and 2.0 g/kg,respectively)were fed to spotted sea bass(Lateolabrax maculatus)in similar size(30.28±0.18 g)in current study.The effects of PCP on growth,physiological parameters,and lipid metabolism of spotted sea bass were investigated after a 4-week rearing period.Results showed,fish with PCP intake presented a significantly higher weight gain,specific growth rate,and a significantly lower feed conversion ratio.Significantly higher trypsin activity in liver and intestine were observed in fish with PCP intake.The superoxide dismutase activity in serum and liver of fish with PCP intake were significantly improved,while significantly higher serum total antioxidant capacity and hepatic catalase activity were also observed.However,no significant differences in lysozyme and alkaline phosphatase activity were evident among groups.Fish with PCP intake showed a significantly lower total cholesterol,but no noteworthy change in triglyceride and lipid-metabolismrelated genes expression were observed among groups.Results indicated that intake of PCP has a positive effect on growth and antioxidant capacity of spotted sea bass,but seems to have a limited effect on the non-specific immunity and lipid metabolism of spotted sea bass.Based on the regression analysis results,1.4 g/kg of PCP is the optimal dose for spotted sea bass in size(30.28±0.18 g).
基金supported by the National Natural Science Foundation of China(Grant Nos.:22176195 and 82127801)National Key R&D Program of China(Grant No.:2022YFF0705003)+5 种基金the Shenzhen Key Laboratory of Precision Diagnosis and Treatment of Depression(Grant No.:ZDSYS20220606100606014)the Guangdong Province Zhu Jiang Talents Plan,China(Grant No.:2021QN02Y028)the Natural Science Foundation of Guangdong Province,China(Grant No.:2021A1515010171)the Key Program of Fundamental Research in Shenzhen,China(Grant No.:JCYJ20210324115811031)the Sustainable Development Program of Shenzhen,China(Grant No.:KCXFZ202002011008124)the National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital&Shenzhen Hospital,Chinese Academy of Medical Sciences and Peking Union Medical College,Shenzhen(Grant Nos.:SZ2020ZD002 and SZ2020QN005).
文摘Esophageal cancer is an upper gastrointestinal malignancy with a bleak prognosis.It is still being explored in depth due to its complex molecular mechanisms of occurrence and development.Lipids play a crucial role in cells by participating in energy supply,biofilm formation,and signal transduction processes,and lipid metabolic reprogramming also constitutes a significant characteristic of malignant tumors.More and more studies have found esophageal cancer has obvious lipid metabolism abnormalities throughout its beginning,progress,and treatment resistance.The inhibition of tumor growth and the enhancement of antitumor therapy efficacy can be achieved through the regulation of lipid metabolism.Therefore,we reviewed and analyzed the research results and latest findings for lipid metabolism and associated analysis techniques in esophageal cancer,and comprehensively proved the value of lipid metabolic reprogramming in the evolution and treatment resistance of esophageal cancer,as well as its significance in exploring potential therapeutic targets and biomarkers.
基金supported by Jiangsu Innovative Group of Meat Nutrition,Health and Biotechnologythe Postgraduate Research&Practice Innovation Program of Jiangsu Province(grant number:KYCX21_0575)。
文摘To determine the effects of plant-based meat analogues on the metabolic health and the possible mechanisms,mice were fed with a real pork diet(AP),a real beef diet(AB),a plant-based pork analogue diet(PP)and plant-based beef analogue diet(PB)for 68 days.Compared with real meat,the plant-based meat analogues increased food and energy intake,body weight,white fat and liver weight and caused adipocyte hypertrophy,hepatic lipid droplet accumulation,and inflammatory responses in mice.Metabolomics revealed that plantbased meat analogues altered the composition of serum metabolites,which regulated lipid metabolism homeostasis.The PB diet upregulated gene expression related to lipid synthesis,lipolysis and adipocyte differentiation while the PP diet upregulated expression of lipolysis-related genes but downregulated expression of adipocyte differentiation-related genes in white adipose tissue.Meanwhile,both PP and PB diets upregulated lipid influx-and synthesis-related genes but downregulated lipid oxidation-related genes in liver.The specific metabolite biomarkers may affect fat accumulation mainly by direct lipid metabolism pathways or indirect amino acid metabolism,protein digestion and absorption,bile secretion,aminoacyl-tRNA biosynthesis,neuroactive ligand-receptor interaction and ABC transporters pathways.These findings provide a new insight into understanding the differences in nutritional functions of meat and plant-based meat analogues.
基金supported by the National Natural Science Foundation of China (32021005, 31820103010)111 project (BP0719028)the Collaborative Innovation Center of Food Safety and Quality Control in Jiangsu Province。
文摘Lactobacillus are considered promising therapeutic methods for nonalcoholic fatty liver disease(NAFLD).The effects of two strains of Ltmosilactobacillus mucosae on NAFLD were investigated in this study.Fourweek-old male C57BL/6J mice were divided into 4 groups(n=8 per group,Control,Model,FZJTZ26M3,FGSYC17L3).L.mucosae FZJTZ26M3 reduced the mice 's body weight,liver weight,and adipose tissue weight after 12 weeks of therapy.According to serum analysis,total cholesterol,triacylglycerol,and low-density lipoprotein cholesterol significantly decreased after L.mucosae FZJTZ26M3 intervention.Liver pathology showed that L.mucosae FZJTZ26M3 was effective to ameliorate lipid deposition in NAFLD mice.Additionally,the expression of the gene related to lipid metabolism in the liver and adipose tissue was analyzed,and the results indicated that L.mucosae FZJTZ26M3 could alleviate NAFLD by regulating lipid metabolism.Furthermore,the results of 16S rRNA gene sequencing revealed a drop in the relative abundance of Ruminococcaceae,which is linked to inflammation,but the relative abundance of a potential probiotic Akkermansia significantly increased after L.mucosae FZJTZ26M3 intervention.Generally,L.mucosae FZJTZ26M3 could be a candidate to prevent NAFLD.
基金supported by the grants from National Natural Science Foundation of China(No.82174334)Hainan Provincial Key Laboratory of Tropical Brain Science Research and Transformation Research Project(JCKF2021001)Innovative Research Projects for Graduate Students(HYYS2021B01).
文摘Background:In this study,we used network pharmacology and molecular docking combined with vitro experiments to explore the potential mechanism of action of Gualou Qumai pill(GLQMP)against DKD.Methods:We screened effective compounds and drug targets using Chinese medicine systemic pharmacology database and analysis platform and Chinese medicine molecular mechanism bioinformatics analysis tools;and searched for DKD targets using human online Mendelian genetics and gene cards.The potential targets of GLQMP for DKD were obtained through the intersection of drug targets and disease targets.Cytoscape software was applied to build herbal medicine-active compound-target-disease networks and analyze them;protein-protein interaction networks were analyzed using the STRING database platform;gene ontology and Kyoto Encyclopedia of Genes and Genomes were used for gene ontology and gene and genome encyclopedia to enrich potential targets using the DAVID database;and the AutoDock Vina 1.1.2 software for molecular docking of key targets with corresponding key components.In vitro experiments were validated by CCK8,oil red O staining,TC,TG,RT-qPCR,and Western blot.Results:Through network pharmacology analysis,a total of 99 potential therapeutic targets of GLQMP for DKD and the corresponding 38 active compounds were obtained,and 5 core compounds were identified.By constructing the protein-protein interaction network and performing network topology analysis,we found that PPARA and PPARG were the key targets,and then we molecularly docked these two key targets with the 38 active compounds,especially the 5 core compounds,and found that PPARA and PPARG had good binding ability with a variety of compounds.In vitro experiments showed that GLQMP was able to ameliorate HK-2 cell injury under high glucose stress,improve cell viability,reduce TC and TG levels as well as decrease the accumulation of lipid droplets,and RT-qPCR and Western blot confirmed that GLQMP was able to promote the expression levels of PPARA and PPARG.Conclusion:Overall,this study revealed the active compounds,important targets and possible mechanisms of GLQMP treatment for DKD,and conducted preliminary verification experiments on its correctness,provided novel insights into the treatment of DKD by GLQMP.
基金sponsored by the Natural Science Foundation of Zhejiang Province (LQ22C200002)Shenzhen Peacock Talent Programs Research Start-up Grant (802-012677)Shenzhen Key Laboratory Foundation (ZDSYS20200811143757022)。
文摘Currently, accumulating pieces of evidence indicate that probiotics, living in the gastrointestinal tract, play an important role in regulating host metabolism. As a tool, probiotics have great potential for treating lipid metabolism diseases. However, the relationship between probiotics and abnormal lipid metabolism is still unclear, and the mechanism of action has been become a focus of microbiome research. Therefore, taking intestinal probiotics as the starting point, this article combs the relationship between probiotics and lipid metabolism. Moreover, we discuss the underlying mechanisms of intestinal probiotics regulating lipid metabolism and summarize the therapeutic strategies for abnormal lipids metabolism. This article provides a reference for the further utilization of probiotics in the field of functional foods(food industry). Meanwhile, it will benefit the clinical diagnosis and treatment of lipid metabolism diseases.
基金This work was supported by grants from the National Natural Science Foundation of China(Nos.81672637 and 81872164).
文摘Tumorigenesis involves metabolic reprogramming and abnormal lipid metabolism,which is manifested by increased endogenous fat mobilization,hypertriglyceridemia,and increased fatty acid synthesis.Fatty acid synthase(FASN)is a key enzyme for the de novo synthesis of fatty acids,and monoacylglycerol esterase(MGLL)is an important metabolic enzyme that converts triglycerides into free fatty acids.Both enzymes play an important role in lipid metabolism and are associated with tumor-related signaling pathways,the most common of which is the PI3K–AKT signaling pathway.They can also regulate the immune microenvironment,participate in epithelial–mesenchymal transition,and then regulate tumor invasion and metastasis.Current literature have shown that these two genes are abnormally expressed in many types of tumors and are highly correlated with tumor migration and invasion.This article introduces the structures and functions of FASN and MGLL,their relationship with abnormal lipid metabolism,and the mechanism of the regulation of tumor invasion and metastasis and reviews the research progress of the relationship of FASN and MGLL with tumor invasion and metastasis.
基金funded by the Projects of China Agriculture Research System(CARS-38)Key Subject of Ningxia Province(2018BBF02016)。
文摘Background Lipid metabolism differs significantly between grazing and stall-feeding lambs,affecting the quality of livestock products.As two critical organs of lipid metabolism,the differences between feeding patterns on rumen and liver metabolism remain unclear.In this study,16S rRNA,metagenomics,transcriptomics,and untargeted metabolomics were utilized to investigate the key rumen microorganisms and metabolites,as well as liver genes and metabolites associated with fatty acid metabolism under indoor feeding(F)and grazing(G).Results Compared with grazing,indoor feeding increased ruminal propionate content.Using metagenome sequencing in combination with 16S rRNA amplicon sequencing,the results showed that the abundance of propionate-producing Succiniclasticum and hydrogenating bacteria Tenericutes was enriched in the F group.For rumen metabolism,grazing caused up-regulation of EPA,DHA and oleic acid and down-regulation of decanoic acid,as well as,screening for 2-ketobutyric acid as a vital differential metabolite,which was enriched in the propionate metabolism pathway.In the liver,indoor feeding increased 3-hydroxypropanoate and citric acid content,causing changes in propionate metabolism and citrate cycle,while decreasing the ETA content.Then,the liver transcriptome revealed that 11 lipid-related genes were differentially expressed in the two feeding patterns.Correlation analysis showed that the expression of CYP4A6,FADS1,FADS2,ALDH6A1 and CYP2C23 was significantly associated with the propionate metabolism process,suggesting that propionate metabolism may be an important factor mediating the hepatic lipid metabolism.Besides,the unsaturated fatty acids in muscle,rumen and liver also had a close correlation.Conclusions Overall,our data demonstrated that rumen microbial-driven metabolite from grazing lambs potentially regulates multiple hepatic lipid-related genes,ultimately affecting body fatty acid metabolism.
基金supported by the General Program of National Natural Science Foundation of China(81673836)。
文摘Objective:To investigate the proteomic characteristics of overweight/obesity and related abnormal glucose and lipid metabolism caused by phlegm-dampness retention to identify related biomarkers.Methods:Seventy-one subjects were enrolled in the study.We assessed blood glucose,blood lipids,body mass index(BMI),and phlegm-dampness pattern,which was confirmed by a traditional Chinese medicine clinician.Of the participants,we included healthy participants with normal weight(NW,n=23),overweight/obese participants with normal metabolism(ONM,n=19),overweight/obese participants with pre-diabetes(OPD,n=12),and overweight/obese participants with marginally-elevated blood lipids(OML,n=17).Among them,the ONM,OPD,and OML groups were diagnosed with phlegmdampness pattern.The data-independent acquisition(DIA)method was first used to analyze the plasma protein expression of each group,and the relevant differential proteins of each group were screened.The co-expressed proteins were evaluated by Venn analysis.The pathway analyses of the differential proteins were analyzed using Ingenuity Pathway Analysis(IPA)software.Parallel reaction monitoring(PRM)was used to verify the differential and common proteins in each group.Results:After comparing ONM,OPD,and OML groups with NW group,we identified the differentially expressed proteins(DEPs).Next,we determined the DEPs among OPD,OML,and ONM groups.Using Venn analysis of the DEPs in each group,24 co-expressed proteins were screened.Two co-expressed proteins were verified by PRM.IPA analysis showed that pathways including LXR/RXR activation,acute phase response signaling,and FXR/RXR activation were common to all three groups of phlegmdamp overweight/obesity participants.However,the activation or inhibition of these pathways was different among the three groups.Conclusion:Participants with overweight/obesity have similar proteomic characteristics,though each type shows specific proteomic characteristics.Two co-expressed proteins,VTN and ORM1,are potential biomarkers for glucose and lipid metabolism diseases with overweight/obesity caused by phlegmdampness retention.
基金supported by grants from Key laboratory of Ecology and Environment in Minority Area,National Ethnic Affairs Commission(KLEEMA202207)the Graduate Research and Practice Projects of Minzu University of China(BZKY2022042).
文摘Night lighting has been shown to affect wild animals.To date,the effects of night lighting on the metabolic homeostasis of birds that spend short time in urban environments remain unclear.Using model bird species Zebra Finch(Taeniopygia guttata),we investigated the effects of short-term night lighting on liver transcriptome,blood glucose,triglyceride,and thyroxine(T4 and T3)levels in birds exposed to two different night lighting duration periods(three days and six days).After three days of night lighting exposure,the expression of genes involved in fat synthesis in the liver was upregulated while the expression of genes involved in fatty acid oxidation and triglyceride decomposition was downregulated.There was also a reduction in blood triglyceride,glucose,and T3 concentrations.However,after six days of night lighting,the expression of genes associated with fatty acid decomposition and hyperglycemia in the liver was upregulated,while the expression of genes involved in fat synthesis was downregulated.Simultaneously,blood glucose levels and T3 concentration increased.These findings indicate that short-term exposure to night lighting can disrupt the lipid and glucose metabolism of small passerine birds,and longer stopovers in urban area with intense night lighting may cause birds to consume more lipid energy.
基金supported by the National Natural Science Foundation of China(31501977)the Sichuan Provincial Key R&D Project,China(22ZDYF0194)+1 种基金the Fundamental Research Funds for the Central Universities of Southwest Minzu University(2021PTJS20)the Innovation Team Development Funds for Sichuan Mutton Sheep,China(cxtd2019–14).
文摘Forty-eight male Lezhi black goat kids with similar body weight((12.09±1.70)kg)and age((60±5)d)were used to determine the effect of dietary copper(Cu),in the form of reagent grade Cu sulfate(CuSO4∙5H2O),on performance,serum lipid profile,and the relative mRNA abundance of genes involved in lipid metabolism.Goat kids were stratified by body weight and randomly assigned to one of 4 treatment groups.Each treatment consisted of 12 replicate pens with each pen containing one goat kid.Treatment groups received the basal diet with no supplemental Cu(control),basal diet plus 10 mg of Cu kg^(-1)of dry matter(DM),basal diet plus 20 mg of Cu kg^(-1)of DM,or basal diet plus 30 mg of Cu kg^(-1)of DM.Goats were housed individually in pens and fed a high-concentrate pelleted diet for 60 d.Average daily gain,average daily feed intake and feed:gain of goats were not affected by dietary Cu supplementation(P>0.10).No differences were detected in serum total cholesterol,triglyceride,and high density lipoprotein cholesterol concentrations of goat kids fed with different Cu concentrations(P>0.05).However,serum low density lipoprotein cholesterol concentrations decreased linearly(P=0.01)as the concentration of dietary Cu increased.Intramuscular fat content of longissimus muscle increased(P=0.002)quadratically and liver Cu concentrations increased(P<0.001)linearly as dietary Cu concentration increased.Compared with the control,dietary supplementation of 20 mg Cu kg^(-1)DM decreased the relative mRNA abundance of fatty acid-binding protein 4(P=0.01)and lipoprotein lipase(P=0.05),and tended to decrease the relative mRNA abundance of carnitine palmitoyltransferase I(P=0.06)in longissimus muscle of goats.The relative mRNA abundance of peroxisome proliferator-activated receptor alpha(P<0.001),carnitine acetyltransferase(P=0.001),and carnitine palmitoyltransferase Ⅰ(P=0.001)were also decreased in liver by Cu supplementation.These results indicate that dietary supplementation of Cu modified lipid metabolism by increasing muscular fat and decreasing serum low density lipoprotein cholesterol,and the modification might be associated with the reduction of relative mRNA abundance of genes for oxidation of long-chain fatty acid in muscle and liver of Lezhi black goat kids.
基金supported by the Tianjin Science and Technology Project(21ZYJDJC00080)and(20ZYJDJC00120)the Natural Science Foundation of Tianjin(18JCZDJC97700)the Natural Science Foundation of China(81573547).
文摘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.
基金supported by the National Natural Science Foundation of China (No.31802101)the Fundamental Research Funds for the Central Universities (No.KJQN201935)。
文摘Background Intrauterine growth restriction(IUGR)can cause lipid disorders in infants and have long-term adverse effects on their growth and development.Clostridium butyricum(C.butyricum),a kind of emerging probiotics,has been reported to effectively attenuate lipid metabolism dysfunctions.Therefore,the objective of this study was to investigate the effects of C.butyricum supplementation on hepatic lipid disorders in IUGR suckling piglets.Methods Sixteen IUGR and eight normal birth weight(NBW)neonatal male piglets were used in this study.From d 3to d 24,in addition to drinking milk,the eight NBW piglets(NBW-CON group,n=8)and eight IUGR piglets(IUGR-CON group,n=8)were given 10 mL sterile saline once a day,while the remaining IUGR piglets(IUGR-CB group,n=8)were orally administered C.butyricum at a dose of 2×108colony-forming units(CFU)/kg body weight(suspended in 10 mL sterile saline)at the same frequency.Results The IUGR-CON piglets exhibited restricted growth,impaired hepatic morphology,disordered lipid metabolism,increased abundance of opportunistic pathogens and altered ileum and liver bile acid(BA)profiles.However,C.butyricum supplementation reshaped the gut microbiota of the IUGR-CB piglets,characterized by a decreased abundance of opportunistic pathogens in the ileum,including Streptococcus and Enterococcus.The decrease in these bile salt hydrolase(BSH)-producing microbes increased the content of conjugated BAs,which could be transported to the liver and function as signaling molecules to activate liver X receptorα(LXRα)and farnesoid X receptor(FXR).This activation effectively accelerated the synthesis and oxidation of fatty acids and down-regulated the total cholesterol level by decreasing the synthesis and promoting the efflux of cholesterol.As a result,the growth performance and morphological structure of the liver improved in the IUGR piglets.Conclusion These results indicate that C.butyricum supplementation in IUGR suckling piglets could decrease the abundance of BSH-producing microbes(Streptococcus and Enterococcus).This decrease altered the ileum and liver BA profiles and consequently activated the expression of hepatic LXRαand FXR.The activation of these two signaling molecules could effectively normalize the lipid metabolism and improve the growth performance of IUGR suckling piglets.
基金funded by Chinese Academy of Sciences(Strategic Priority Research Program Grant NO.XDA26040304,XDA26050102)CAS Science and Technology Service Network Initiative(KFJ-STS-ZDTP-075)Innovation Province Project(2019RS3021)。
文摘Background:Methionine or lysine has been reported to influence DNA methylation and fat metabolism,but their combined effects in N6-methyl-adenosine(m^(6)A)RNA methylation remain unclarified.The combined effects of rumen-protected methionine and lysine(RML)in a low-protein(LP)diet on lipid metabolism,m^(6)A RNA methylation,and fatty acid(FA)profiles in the liver and muscle of lambs were investigated.Sixty-three male lambs were divided into three treatment groups,three pens per group and seven lambs per pen.The lambs were fed a 14.5%crude protein(CP)diet(adequate protein[NP]),12.5%CP diet(LP),and a LP diet plus RML(LP+RML)for 60 d.Results:The results showed that the addition of RML in a LP diet tended to lower the concentrations of plasma leptin(P=0.07),triglyceride(P=0.05),and non-esterified FA(P=0.08).Feeding a LP diet increased the enzyme activity or m RNA expression of lipogenic enzymes and decreased lipolytic enzymes compared with the NP diet.This effect was reversed by supplementation of RML with a LP diet.The inclusion of RML in a LP diet affected the polyunsaturated fatty acids(PUFA),n-3 PUFA,and n-6 PUFA in the liver but not in the muscle,which might be linked with altered expression of FA desaturase-1(FADS1)and acetyl-Co A carboxylase(ACC).A LP diet supplemented with RML increased(P<0.05)total m^(6)A levels in the liver and muscle and were accompanied by decreased expression of fat mass and obesity-associated protein(FTO)and alk B homologue 5(ALKBH5).The m RNA expressions of methyltransferase-like 3(METTL3)and methyltransferase-like 14(METTL14)in the LP+RML diet group were lower than those in the other two groups.Supplementation of RML with a LP diet affected only liver YTH domain family(YTHDF2)proteins(P<0.05)and muscle YTHDF3(P=0.09),which can be explained by limited m^(6)Abinding proteins that were mediated in m RNA fate.Conclusions:Our findings showed that the inclusion of RML in a LP diet could alter fat deposition through modulations of lipogenesis and lipolysis in the liver and muscle.These changes in fat metabolism may be associated with the modification of m^(6)A RNA methylation.
基金supported by National Natural Science Foundation of China (31271855)the ThirteenFifth Mega-Scientific Project (2017ZX10201301-003-003)+1 种基金Wuhan science and technology project (2018020402011230)the central government guides local science and technology development projects (2019ZYYD)。
文摘Scope: Circadian disorder and high-fat diet(HFD)can disturb lipid metabolism homeostasis and may promote the development of various metabolic diseases. The relationship between them is of great concern. This study aimed to explore the effects of Per1/Per2 double knockout(DKO)on hepatic lipid metabolism in mice under HFD and HFD with docosahexaenoic acid(DHA)substitution. Methods and results: Both wild type(WT)and DKO male C57BL/6 mice were fed with normal chow diet(CON), HFD, or HFD with DHA substitution(AO)for 15 weeks. At the end of the experiment, mice were sacrificed at zeitgeber time(ZT)0(7:00 am)or ZT12(7:00 pm). Pathological indicators were determined using histological and biochemical methods. Hepatic transcriptome sequencing analysis showed that DKO mice exhibited multiple dysfunctions in diurnal rhythm, drug metabolism, cell cycle, cancer pathways, and lipid metabolism. HFD had greater effects on fatty acid oxidation and cholesterol synthesis and metabolism in Per1-/-Per2-/-mice, which was improved by DHA substitution. Conclusions: Per1/Per2 played an important role in the circadian regulation of hepatic lipid metabolism, and DKO mice were more sensitive to HFD. DHA can improve circadian-related lipid metabolism disruption induced by HFD in mice.
