Objective:Psoriasis is associated with lipid metabolism disorders,but the underlying mechanisms remain unclear.This study aims to investigate the role of trimethylamine Noxide(TMAO)in lipid metabolism dysregulation in...Objective:Psoriasis is associated with lipid metabolism disorders,but the underlying mechanisms remain unclear.This study aims to investigate the role of trimethylamine Noxide(TMAO)in lipid metabolism dysregulation in psoriasis.Methods:An imiquimod(IMQ)-induced psoriasis-like mouse model was used to assess lipid metabolism parameters,TMAO levels,and liver flavin monooxygenase 3(FMO3)mRNA expression.Blood samples from healthy individuals and psoriatic patients were collected to measure serum TMAO levels and lipid profiles.To clarify the role of TMAO in the lipid metabolism disorder of mice with psoriasis model,exogenous TMAO,choline,or 3,3-dimethyl-1-butanol(DMB)were administered via intraperitoneal injections or diet in IMQ-treated mice.Liver tissues from the mouse models were subjected to RNA sequencing to identify TMAO-regulated signaling pathways.Results:IMQ-induced psoriatic mice exhibited abnormal glucose,insulin,and lipid levels.IMQ treatment also downregulated the hepatic mRNA expression of glucose transporter 2(Glut2)and silence information regulator 1(Sirt1),while upregulating glucose transporter 4(Glut4)and peroxisome proliferator-activated receptor gamma(PPARγ).Elevated serum TMAO levels were observed in both psoriatic patients and IMQ-treated mice.Additionally,liver FMO3 mRNA expression was increased in the psoriatic mouse model.In patients,TMAO levels positively correlated with Psoriasis Area and Severity Index(PASI)scores,serum triglyceride(TG),and total cholesterol(TC)levels.The intraperitoneal injection of TMAO exacerbated lipid dysregulation in IMQ-treated mice.A choline-rich diet further aggravated lipid abnormalities and liver injury in psoriatic mice,whereas DMB treatment alleviated these effects.RNA-Seq analysis demonstrated that TMAO upregulated hepatic microRNA-122(miR-122),which may suppress the expression of gremlin 2(GREM2),thus contributing to lipid metabolism disorder.Conclusion:TMAO may promote lipid metabolism dysregulation in psoriasis by modulating the hepatic miR-122/GREM2 pathway.展开更多
Background:The emerging incidence of pathogenic liver conditions is turning into a major concern for global health.Induction of pyroptosis in hepatocytes instigates cel-lular disintegration,which in turn liberates sub...Background:The emerging incidence of pathogenic liver conditions is turning into a major concern for global health.Induction of pyroptosis in hepatocytes instigates cel-lular disintegration,which in turn liberates substantial quantities of pro-inflammatory intracellular substances,thereby accelerating the advancement of liver fibrosis.Consequently,directing therapeutic efforts towards inhibiting pyroptosis could po-tentially serve as an innovative approach in managing inflammation related chronic hepatic disorders.Methods:GSDMD-NT^(ki/wt)mice and Alb-cre^(ki/wt)mice were generated using CRISPR/Cas9 technology.After crossing the two strains together,we induced conditional cell death by doxycycline to construct a mouse model of liver fibrosis.We analyzed differ-entially expressed genes by RNA sequencing and explored their biological functions.The efficacy of obeticholic acid(OCA)in the treatment of liver fibrosis was assessed.Results:Doxycycline-treated GSDMD-NT^(ki/wt)×Alb-cre^(ki/wt)mice showed severe liver damage,vacuolation of hepatocytes,increased collagen fibers,and accumulation of lipid droplets.The expression of liver fibrosis related genes was greatly increased in the doxycycline-treated mouse liver compared with untreated mouse liver.RNA-sequencing showed that upregulated differentially expressed genes were involved in inflammatory responses,cell activation,and metabolic processes.Treatment with OCA alleviated the liver fibrosis,with reduced ALT and AST levels seen in the GSDMD-NT^(ki/wt)×Alb-cre^(ki/wt)mice.Conclusions:We successfully constructed a novel mouse model for liver fibrosis.This GSDMD-NT-induced fibrosis may be mediated by abnormal lipid metabolism.Our re-sults demonstrated that we successfully constructed a mouse model of liver fibrosis,and GSDMD-NT induced fibrosis by mediating lipid metabolism.展开更多
Background The objective of this study was to evaluate the effects of dietary fatty acids(FA)saturation and lysophospholipids supplementation on growth,meat quality,oxidative stability,FA profiles,and lipid metabolism...Background The objective of this study was to evaluate the effects of dietary fatty acids(FA)saturation and lysophospholipids supplementation on growth,meat quality,oxidative stability,FA profiles,and lipid metabolism of finishing beef bulls.Thirty-two Angus bulls(initial body weight:623±22.6 kg;21±0.5 months of age)were used.The experiment was a completely randomized block design with a 2×2 factorial arrangement of treatments:2 diets with FA of different degree of unsaturation[high saturated FA diet(HSFA)vs.high unsaturated FA diet(HUFA)]combined with(0.075%,dry matter basis)and without lysophospholipids supplementation.The bulls were fed a high-concentrate diet(forage to concentrate,15:85)for 104 d including a 14-d adaptation period and a 90-d data and sample collection period.Results No interactions were observed between dietary FA and lysophospholipids supplementation for growth and meat quality parameters.A greater dietary ratio of unsaturated FA(UFA)to saturated FA(SFA)from 1:2 to 1:1 led to lower DM intake and backfat thickness,but did not affect growth performance and other carcass traits.Compared with HSFA,bulls fed HUFA had greater shear force in Longissimus thoracis(LT)muscle,but had lower intramuscular fat(IMF)content and SOD content in LT muscle.Compared with HUFA,feeding the HSFA diet up-regulated expression of ACC,FAS,PPARγ,and SCD1,but down-regulated expression of CPT1B.Compared with feeding HSFA,the HUFA diet led to greater concentrations of c9-C18:1 and other monounsaturated FA in LT muscle.Feeding HUFA also led to lower plasma concentrations of cholesterol,but there were no interactions between FA and lysophospholipids detected.Feeding lysophospholipids improved growth and feed conversion ratio and altered meat quality by increasing muscle pH_(24h),redness values(24 h),IMF content,and concentrations of C18:3,C20:5 and total polyunsaturated fatty acids.Furthermore,lysophospholipids supplementation led to lower malondialdehyde content and up-regulated the expression of ACC,FAS,and LPL in LT muscle.Conclusions Results indicated that supplementing a high-concentrate diet with lysophospholipids to beef bulls can enhance growth rate,feed efficiency,meat quality,and beneficial FA.Increasing the dietary ratio of UFA to SFA reduced DM intake and backfat thickness without compromising growth,suggesting potential improvements in feed efficiency.展开更多
Background:It is widely accepted that an alteration in lipid metabolism can serve as an essential hallmark for the growth and progression of various malignancies.However,the potential of lipid metabolism genes(LMGs)an...Background:It is widely accepted that an alteration in lipid metabolism can serve as an essential hallmark for the growth and progression of various malignancies.However,the potential of lipid metabolism genes(LMGs)and related pathways as drug targets for rectal adenocarcinoma(READ)treatment and prognostic evaluation requires further investigation.The objective of the present study was to construct a prognostic prediction model for READ based on LMGs,and to evaluate its performance.Methods:The RNA-seq FPKM data and clinical data from READ patients and normal rectal tissues were downloaded from The Cancer Genome Atlas database.The LMGs were acquired from the Molecular Signatures Database.Subsequently,LMGs associated with the prognosis of READ were screened,and these genes were used to construct a prognostic prediction model for READ patients.The model was then subjected to rigorous evaluation.Furthermore,immune infiltration and limma analyses were performed in different clusters,and pathway enrichment analyses were performed on the screened differentially expressed genes(DEGs).Results:A prognostic prediction model was constructed based on 5 LMGs(PLA2G2F,CBR1,CHKB,ETNPPL,and ARV1)to classify READ into high-and low-risk groups,with the low-risk group exhibiting a higher survival rate.Consequently,the prognostic model demonstrated notable predictive capability.A total of 139 DEGs were identified,38 of which were identified as being upregulated and 101 as being downregulated.Furthermore,a comparison of the immune microenvironment and immune pathways between the low-and high-risk groups revealed significant disparities.Conclusions:Predictive models based on 5 lipid metabolism DEGs effectively predicted the prognosis of READ patients.Moreover,these 5 LMGs have potential as molecular biomarkers and therapeutic targets for READ patients.展开更多
Obesity caused by poor eating habits has become a global public health issue and harms human health.Rosmarinic acid(RA)is a natural active substance with many biological functions like antioxidant.However,the function...Obesity caused by poor eating habits has become a global public health issue and harms human health.Rosmarinic acid(RA)is a natural active substance with many biological functions like antioxidant.However,the function of RA's lipid-lowering effect and mechanism are not entirely clear.This study aimed to explore the effect of RA on obesity and its action mechanism in Caenorhabditis elegans.RA not only alleviated intestinal inflammation and change the composition of unsaturated fatty acid,but also decreased fat storage and adjusted the size and quantity of fat droplets without threatening development and reproduction or affecting energy intake.In addition,RA improved the integrity of intestinal barrier function in C.elegans.RNA sequencing and quantitative reverse transcription-polymerase chain reaction(qRT-PCR)comprehensively revealed that the lipid-lowering mechanism mediated by RA might involve lipid metabolism and anti-inflammatory pathways.Among them,RA regulates lipid metabolism by reducing fat synthesis through SBP-1 and increasing fatty acidβ-oxidation via NHR-49.Furthermore,the anti-inflammatory pathway was associated with RA's enhancement of the ratio of unsaturated fatty acid and alleviation of inflammatory reactions caused by Pseudomonas aeruginosa(PAO1).Therefore,RA regulated lipid metabolism and relieved inflammation,which had the potential for dietary supplements or functional foods.展开更多
Citrus,which has been consumed internationally for a long time,is widely used as a health food.Citrus and its active components exert significant effects on oxidative stress and lipid metabolism,which are closely asso...Citrus,which has been consumed internationally for a long time,is widely used as a health food.Citrus and its active components exert significant effects on oxidative stress and lipid metabolism,which are closely associated with female reproductive health.Studies suggest that citrus-derived compounds may alleviate oxidative stress by activating signaling pathways such as nuclear factor erythroid 2-related factor 2(Nrf2)and Sirtuin 1(SIRT1),and improve lipid metabolism through the activation of pathways such as peroxisome proliferator-activated receptorα(PPARα).This review focuses on the effects of Citrus on oxidative stress and lipid metabolism,aiming to provide new insights for promoting female reproductive health;however,further work is needed to elucidate the mechanisms involved and validate the therapeutic potential of Citrus’s bioactive components in clinical settings.展开更多
Background Dysregulation of lipid metabolism and its consequences on growth performance in young ruminants have attracted attention,especially in the context of alternative feeding strategies.This study aims to elucid...Background Dysregulation of lipid metabolism and its consequences on growth performance in young ruminants have attracted attention,especially in the context of alternative feeding strategies.This study aims to elucidate the effects of milk replacer(MR)feeding on growth,lipid metabolism,colonic epithelial gene expression,colonic microbiota composition and systemic metabolism in goat kids compared to breast milk(BM)feeding,addressing a critical knowledge gap in early life nutrition.Methods Ten female goat kids were divided into 2 groups:those fed breast milk(BM group)and those fed a milk replacer(MR group).Over a period of 28 d,body weight was monitored and blood and tissue samples were collected for biochemical,transcriptomic and metabolomic analyses.Profiling of the colonial microbiota was performed using 16S rRNA gene sequencing.Intestinal microbiota transplantation(IMT)experiments in gnotobiotic mice were per-formed to validate causality.Results MR-fed pups exhibited reduced daily body-weight gain due to impaired lipid metabolism as evidenced by lower serum and liver total cholesterol(TC)and non-esterified fatty acid(NEFA)concentrations.Transcriptomic analysis of the colonic epithelium revealed upregulated genes involved in negative regulation of lipid metabolism,concomitant with microbiota shifts characterized by a decrease in Firmicutes and an increase in Actinobacteria.Specifically,genera such as Bifidobacterium and Prevotella were enriched in the MR group,while Clostridium and Fae-calibacterium were depleted.Metabolomics analyses confirmed alterations in bile acid and fatty acid metabolic path-ways.IMT experiments in mice recapitulated the metabolic phenotype observed in MR-fed goats,confirming the role of the microbiota in modulating host lipid metabolism.Conclusions Milk replacer feeding in goat kids disrupts lipid metabolism and gut microbiota dynamics,result-ing in reduced growth rates and metabolic alterations.These findings highlight the importance of early nutritional intervention on metabolic programming and suggest that modulation of the gut microbiota may be a target for improving growth and metabolic health in ruminants.This study contributes to the understanding of nutritional management strategies in livestock and their impact on animal health and productivity.展开更多
BACKGROUND Probiotic Acetobacter pasteurianus is used to treat diabetes,but its specific hypoglycemic substances and mechanisms remain unclear.AIM To investigate the components for lipid metabolism of A.pasteurianus a...BACKGROUND Probiotic Acetobacter pasteurianus is used to treat diabetes,but its specific hypoglycemic substances and mechanisms remain unclear.AIM To investigate the components for lipid metabolism of A.pasteurianus and its hypoglycemic effects,providing a basis for its broader application.METHODS The lipid metabolism of A.pasteurianus under different growth conditions was analyzed using lipidomics.Neutral lipid staining in A.pasteurianus cells and the formation of lipid droplet-like structures were observed using a confocal laser scanning microscope.The neutral lipid components were also analyzed using thin layer chromato-graphy.A diabetic mouse model was established to evaluate the hypoglycemic effects of the main lipid components of A.pasteurianus and their role in repairing tissues such as the pancreas.RESULTS After comparing the effects of three culture media,namely,brain heart infusion(BHI)medium with 2%glucose,chromium-rich and zinc-rich medium,and mineral salt medium,A.pasteurianus grew well in BHI containing 2%glucose and produced the most lipids.A total of 583 lipid metabolic products was identified,with higher levels of coenzyme Q9(CoQ9),oleic acid(OA),and wax ester,but no triacylglycerol was observed.It was found that the components that affected lipid metabolism in A.pasteurianus were mainly CoQ9 and OA.They exhibited hypoglycemic effects comparable to metformin in diabetic mice,repaired damaged pancreatic tissues,and did not cause damage to the liver and spleen.CONCLUSION Under high-nutrient growth conditions,A.pasteurianus contains abundant lipid components,such as CoQ9 and OA,with good hypoglycemic effects.展开更多
Seed germination plays a pivotal role in plant growth and undergoes many intricate biochemical changes including lipid metabolism.Nevertheless,little is known about lipid changes and distributions in different structu...Seed germination plays a pivotal role in plant growth and undergoes many intricate biochemical changes including lipid metabolism.Nevertheless,little is known about lipid changes and distributions in different structures of soybean seeds during germination.Here,we applied mass spectrometry imaging(MSI)in conjunction with MS-based lipidomics to examine the lipid alterations in the embryo and cotyledon of soybean seeds during germination.To expand the coverage of lipid detection in soybean seeds,we used the novel techniques of matrix-assisted laser desorption/ionization(MALDI)and MALDI coupled with laser-postionization(MALDI-2).The results revealed that compared to MALDI,MALDI-2 enhanced the detected numbers and intensities of lipid species in various lipid classes,except for a few classes(e.g.,sphingomyelin and phosphatidylcholine).Lipidomic data showed that compared to the embryo,the cotyledon demonstrated slower but similar lipid changes during germination.These changes included the reduced levels of glycerolipids,phospholipids,and sterols,as well as the increased levels of lysophospholipids.Data from MALDI&MALDI-2 MSI supported and complemented these lipidomic findings.Our work highlights the significance of integrating lipid profiles and distributions to enhance our understanding of the metabolic pathways involved in seed germination.展开更多
Lipid metabolism plays a pivotal role in gastric cancer(GC)progression,characterized by complex metabolic reprogramming that supports tumor growth and survival.This narrative review comprehensively examines the dysreg...Lipid metabolism plays a pivotal role in gastric cancer(GC)progression,characterized by complex metabolic reprogramming that supports tumor growth and survival.This narrative review comprehensively examines the dysregulation of lipid metabolism-associated genes,including fatty acid synthase(FASN),ATPcitrate lyase,acetyl-CoA carboxylases,FA binding proteins,sterol regulatory element-binding proteins,and other key enzymes.These genes facilitate critical oncogenic processes by enhancing FA synthesis,modifying cellular signaling,and supporting cancer cell proliferation,migration,and therapy resistance.Metabolic adaptations observed in GC include increased de novo lipogenesis,altered enzymatic activities,and modified protein lipidation,which contribute to tumor aggressiveness.The review highlights the potential of targeting these metabolic pathways as a therapeutic strategy,demonstrating how inhibiting specific enzymes like FASN,ATP-citrate lyase,and stearoyl-CoA desaturase 1 can induce apoptosis,disrupt cancer stem cell properties,and potentially overcome treatment resistance.By elucidating the intricate interactions between lipid metabolism genes and cancer progression,this review provides insights into novel diagnostic and therapeutic approaches for managing GC.展开更多
The global prevalence of myopia is becoming increasingly severe,with epidemiological models predicting that by 2050,approximately 50%of the world’s population will be affected by myopia,and about 10%will suffer from ...The global prevalence of myopia is becoming increasingly severe,with epidemiological models predicting that by 2050,approximately 50%of the world’s population will be affected by myopia,and about 10%will suffer from high myopia.The incidence of high myopia is projected to increase fivefold,making it the leading cause of irreversible vision impairment.Myopia often leads to various complications and has been associated with other ocular diseases,including early-onset cataracts,age-related macular degeneration,and primary open angle glaucoma.As a result,the control and management of myopia have become ongoing and long-term research priorities.The pathogenesis of myopia involves complex multisystem interactions.Current mainstream theories focus primarily on choroidal hypoxia-induced scleral remodeling,with neurotransmitters such as acetylcholine and dopamine playing regulatory roles.However,recent studies have increasingly suggested that changes in nutritional intake,including proteins,fats,and cholesterol,may also be related to myopia development.The role of lipid metabolism in the onset and progression of myopia has gradually attracted growing attention.Therefore,this review aims to systematically elucidate the molecular mechanisms of lipid metabolism regulatory networks in axial myopia,integrating multidimensional factors to provide a theoretical foundation for precision intervention strategies.展开更多
Background Porcine epidemic diarrhea virus(PEDV)infection poses a significant challenge to the swine industry,with limited effective control measures available.Poria cocos polysaccharides(PCP)is the primary active ing...Background Porcine epidemic diarrhea virus(PEDV)infection poses a significant challenge to the swine industry,with limited effective control measures available.Poria cocos polysaccharides(PCP)is the primary active ingredient of Poria cocos,and has been demonstrated to show beneficial effects on intestinal damage in previous studies.However,its mechanism has not been fully understood.In the present study,18 seven-day-old piglets were divided into 3 groups:Control group,PEDV group,and PCP+PEDV group.After three days of adaptation,piglets in the PCP+PEDV group were orally administered 10 mg/kg body weight/d PCP from d 4 to 10.On d 8,piglets were orally administered with PEDV at the dose of 104.5 TCID50/piglet.This study aimed to investigate the potential effects of PCP on PEDVinduced intestinal injury and explored the underlying mechanisms.Results The results showed that PCP administration effectively alleviated diarrhea,reduced PEDV replication in the small intestine and colon of piglets,and significantly improved intestinal mucosal morphology.Specifically,PCP increased the villus height in both the jejunum and ileum and increased the villus height to crypt depth ratio in the ileum(P<0.05).Improved intestinal function was further evidenced by elevated plasma D-xylose levels and decreased diamine oxidase activity(P<0.05).Transcriptomic and proteomic analyses revealed that lipid metabolism is a key pathway regulated by PCP during PEDV infection.Notably,PCP significantly upregulated sphingolipid metabolism-related genes,including ectonucleotide pyrophosphatase/phosphodiesterase family member 7 and N-acylsphingosine amidohydrolase 2.Metabolomic analysis revealed that PCP primarily modulated the levels of plasmanylphosphoethanolamine,lysophosphatidylcholine,and carnitine.Additionally,PCP reversed the expression of key genes involved in fatty acid uptake,intracellular lipid transport,and fatty acid synthesis,such as fatty acid binding protein 2,fatty acid transport protein 4,apolipoprotein B,apolipoprotein C3,fatty acid synthase,long-chain fatty acyl CoA synthetase 3,lipoprotein lipase and acyl-CoA thioesterases 12(P<0.05).Conclusions These findings demonstrate that PCP mitigates PEDV-induced intestinal injury by modulating lipid metabolism and highlight its potential as a dietary supplement for enhancing anti-PEDV defenses and promoting intestinal health in piglets.展开更多
Background Regulating the regional deposition of fat is crucial for improving the carcass characteristics of pigs.The intestine,as an important organ for lipid absorption and homeostasis maintenance,secretes various b...Background Regulating the regional deposition of fat is crucial for improving the carcass characteristics of pigs.The intestine,as an important organ for lipid absorption and homeostasis maintenance,secretes various biological signals that participate in the crosstalk between the intestine and adipose tissue.Extracellular vesicles,as novel extracellular genetic factors that mediate metabolic signal exchange among multiple tissues,have emerged as a hotspot and breakthrough in revealing the mechanisms of physiological homeostasis.However,how extracellular vesicles regulate the intestinal-adipose signaling axis,especially in relation lipid metabolism and deposition is still unclear.Thus,in the current study,intestinal extracellular vesicles from Chinese fat-type piglets of Lantang and typical leantype piglets of Landrace were isolated and identified,and to reveal the regulatory mechanisms of lipid metabolism via intestinal extracellular vesicles in mediating intestinal-adipose crosstalk.Results We isolated and identified intestinal extracellular vesicles from the jejunum of 3-day-old Lantang and Landrace piglets(LT-EVs and LD-EVs)and further investigated their effects on lipid accumulation in porcine primary adipocytes.Compared to LD-EVs,LT-EVs promoted lipid deposition in porcine primary adipocytes,with intestinal-derived miRNAs playing a critical role in the crosstalk between the intestine and adipose tissue.Further analysis of extracellular vesicles-derived miRNA sequencing revealed that miR-30b-5p,enriched in LD-EVs,is involved in the regulation of lipid metabolism.Notably,the enrichment of miR-30b-5p in extracellular vesicles derived from IPEC-J2 cells also influenced lipid metabolism.Mechanistically,the targeted binding of miR-30b-5p and FMO3 may be critical for the extracellular vesicle-mediated regulation of lipid metabolism.Conclusions Our findings suggest that jejunal-derived extracellular vesicles play a critical role in regulating lipid metabolism,and the regulatory effect of extracellular vesicles from obese piglets was higher than that of lean piglets.Furthermore,the different expression of miRNAs,such as miR-30b-5p,in intestinal extracellular vesicles may be the key to determining lipid deposition phenotypes across the two pig breeds.展开更多
Neuron-derived clone 77 (Nur77) is a member of the NR4A subfamily that plays critical roles in apoptosis, survival, proliferation, autophagy, angiogenesis, inflammatory responses, DNA repair, glycolipid metabolism and...Neuron-derived clone 77 (Nur77) is a member of the NR4A subfamily that plays critical roles in apoptosis, survival, proliferation, autophagy, angiogenesis, inflammatory responses, DNA repair, glycolipid metabolism and energy consumption. The deregulation of Nur77 signalling often relates to various serious diseases, including cancer and non-cancer diseases. A systematic review is necessary for the better understanding of Nur77 in clinical treatment. In this article, we comprehensively conclude the lipid regulation function and expression of Nur77, and its role in COPD. Finally, we prospect that development of drugs and clinical biochemical investigations targeting of Nur77 has considerable potential within healthcare.展开更多
Objective To clarify the causal relationship between the level of cytoplasmic unactivated mineralocorticoid receptor(MR)and the development of tubulointerstitial nephritis(TIN),and to evaluate the impact of MR on dysl...Objective To clarify the causal relationship between the level of cytoplasmic unactivated mineralocorticoid receptor(MR)and the development of tubulointerstitial nephritis(TIN),and to evaluate the impact of MR on dyslipidemia,particularly secondary hyperlipemia,in patients with diabetic kidney disease.Methods We conducted a two-sample Mendelian randomization study using genome-wide association study(GWAS)summary data.Genetic variants associated with MR levels were selected as exposures,with TIN and lipid profiles[including low-density lipoprotein cholesterol(LDL-C),triglyceride,and high-density lipoprotein cholesterol]as outcomes.A two-step Mendelian randomization approach was used to assess TIN as a mediator,employing inverse variance weighted regression as the primary analysis,supplemented by Mendelian randomization-Egger,weighted median,and sensitivity analyses.Results Cytoplasmic unactivated MR level exhibited a significant causal association with a decreased risk of TIN(OR=0.8598,95%CI[0.7775-0.9508],P<0.001).Although no significant causal relationship was identified between MR level and secondary hyperlipemia,a potential association of cytoplasmic unactivated MR level with lower LDL-C levels was observed(OR=0.9901,95%CI[0.9821-0.9983],P=0.018).Additionally,TIN exhibited causal links with secondary hyperlipemia(OR=1.0016,95%CI[1.0002-1.0029],P=0.020)and elevated LDL-C(OR=1.0111,95%CI[1.0024-1.0199],P=0.012),particularly LDL-C in European males(OR=1.0230,95%CI[1.0103-1.0358],P<0.001).Inverse Mendelian randomization analysis revealed causal relationships between TIN and genetically predicted triglyceride(OR=0.7027,95%CI[0.6189-0.7978],P<0.001),high-density lipoprotein cholesterol(OR=1.1247,95%CI[1.0019-1.2626],P=0.046),and LDL-C(OR=0.8423,95%CI[0.7220-0.9827],P=0.029).Notably,TIN mediated 16.7%of the causal association between MR and LDL-C levels.Conclusions MR plays a critical role in the development of TIN and lipid metabolism,highlighting the potential of MR-antagonists in reducing renal damage and lipid metabolism-associated complications.展开更多
Associations of per-and polyfluoroalkyl substances(PFAS)on lipid metabolism have been documented but research remains scarce regarding effect of PFAS on lipid variability.To deeply understand their relationship,a step...Associations of per-and polyfluoroalkyl substances(PFAS)on lipid metabolism have been documented but research remains scarce regarding effect of PFAS on lipid variability.To deeply understand their relationship,a step-forward in causal inference is expected.To address these,we conducted a longitudinal study with three repeated measurements involving 201 participants in Beijing,among which 100 eligible participants were included for the present study.Twenty-three PFAS and four lipid indicators were assessed at each visit.We used linear mixed models and quantile g-computation models to investigate associations between PFAS and blood lipid levels.A latent class growth model described PFAS serum exposure patterns,and a generalized linear model demonstrated associations between these patterns and lipid variability.Our study found that PFDA was associated with increased TC(β=0.083,95%CI:0.011,0.155)and HDL-C(β=0.106,95%CI:0.034,0.178).The PFAS mixture also showed a positive relationship with TC(β=0.06,95%CI:0.02,0.10),with PFDA contributing most positively.Compared to the low trajectory group,the middle trajectory group for PFDA was associated with VIM of TC(β=0.756,95%CI:0.153,1.359).Furthermore,PFDA showed biological gradientswith lipid metabolism.This is the first repeated-measures study to identify the impact of PFAS serum exposure pattern on the lipid metabolism and the first to estimate the association between PFAS and blood lipid levels in middle-aged and elderly Chinese and reinforce the evidence of their causal relationship through epidemiological studies.展开更多
Lipids are essential for normal life activities and biological functions of the human body,and disorders of lipid metabolism produce a lipotoxic environment,endoplasmic reticulum(ER)stress,inflammation,and cell death,...Lipids are essential for normal life activities and biological functions of the human body,and disorders of lipid metabolism produce a lipotoxic environment,endoplasmic reticulum(ER)stress,inflammation,and cell death,which can lead to a variety of diseases in the body.It has been found that lipid metabolism disorders are closely associated with brain injury disease,cancer,metabolic disease,cardiovascular disease(CVD),respiratory disease and infectious disease.In recent years,many medicinal and edible plants such as Pueraria lobata,Gardenia jasminoides,Curcuma longa,citrus fruits,peanuts,etc.have shown great potential in regulating lipid metabolism and some of the hidden active components showed innovative mechanisms.AMPK,PPARy,SIRT1,Foxp3,NLRP3,and Keapl are increasingly recognized as therapeutic targets in the field of regulating lipid metabolism.This study aims to provide a comprehensive review of natural lipid-regulating modulators in medicinal and edible plants and their mechanism of actions,which offer valuable references for the discovery of natural lipid metabolism modulators and a therapeutic strategy for treatment of lipid metabolism-related diseases.展开更多
Background:Ferroptosis is a type of regulated cell death characterized by iron-dependent lipid peroxidation,which has been linked to tumor progression and therapeutic resistance.However,the contribution of lactate met...Background:Ferroptosis is a type of regulated cell death characterized by iron-dependent lipid peroxidation,which has been linked to tumor progression and therapeutic resistance.However,the contribution of lactate metabolism and its receptor,hydroxycarboxylic acid receptor 1(HCAR1),in ferroptosis regulation in gastric cancer(GC)remains poorly understood.Focusing specifically on its effects on cell proliferation,ferroptosis regulation,and the disruption of lactate-mediatedmetabolic pathways,the study aimed to clarify the role ofHCAR1 in GC progression.Methods:Bioinformatics analysis identified prognostic genes associated with ferroptosis in GC.Receiver operating characteristic(ROC)curves were generated to assess the diagnostic potential of the predictive genes.The biological role of HCAR1 was investigated through gain and loss-of-function experiments in GC cell lines,followed by assessments of cell viability,oxidative stress indicators,gene/protein expression,and ferroptosis sensitivity under lactate stimulation or HCAR1modulation.Results:HCAR1 was significantly upregulated in GC tissues and linked to poor patient outcomes.Silencing HCAR1 inhibited GC cell growth and induced ferroptosis,as shown by increased levels of reactive oxygen species(ROS)and malondialdehyde(MDA),along with decreased expression of solute carrier family 7 member 11(SLC7A11)and glutathione peroxidase 4(GPX4).Conversely,HCAR1 overexpression or exposure to extracellular lactate inhibited ferroptosis and activated antioxidant defenses.Mechanistically,lactate activation of HCAR1 increases ATP levels,which in turn inactivates AMP-activated protein kinase(AMPK).It also upregulates stearoyl-CoA desaturase 1(SCD1)through the sterol regulatory element binding protein 1(SREBP1)signaling pathway.Blocking HCAR1 reversed these effects and restored ferroptosis sensitivity.Conclusion:HCAR1 mediates lactate-driven ferroptosis resistance in GC through the AMPK-SCD1 signaling pathway.Targeting the HCAR1-lactate axis may offer a promising strategy for overcoming metabolic adaptation and improving GC treatment outcomes.展开更多
Ezrin,as a key connecting protein between the cytoskeleton and cell membrane,plays an important role in various cellular physiological processes.In recent years,people have gradually attached importance to its researc...Ezrin,as a key connecting protein between the cytoskeleton and cell membrane,plays an important role in various cellular physiological processes.In recent years,people have gradually attached importance to its research in the field of glucose and lipid metabolism.Based on relevant research materials,this article elaborates the structure and function of Ezrin,and focuses on its role and potential mechanism in the diseases related to abnormal glucose and lipid metabolism,such as diabetes and its complications,to provide new ideas and theoretical basis for in-depth understanding of the regulation of glucose and lipid metabolism and the prevention and treatment of related diseases.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
基金supported by the National Natural Science Foundation(82173426)the Natural Science Foundation of Hunan Province(2023JJ30984),China。
文摘Objective:Psoriasis is associated with lipid metabolism disorders,but the underlying mechanisms remain unclear.This study aims to investigate the role of trimethylamine Noxide(TMAO)in lipid metabolism dysregulation in psoriasis.Methods:An imiquimod(IMQ)-induced psoriasis-like mouse model was used to assess lipid metabolism parameters,TMAO levels,and liver flavin monooxygenase 3(FMO3)mRNA expression.Blood samples from healthy individuals and psoriatic patients were collected to measure serum TMAO levels and lipid profiles.To clarify the role of TMAO in the lipid metabolism disorder of mice with psoriasis model,exogenous TMAO,choline,or 3,3-dimethyl-1-butanol(DMB)were administered via intraperitoneal injections or diet in IMQ-treated mice.Liver tissues from the mouse models were subjected to RNA sequencing to identify TMAO-regulated signaling pathways.Results:IMQ-induced psoriatic mice exhibited abnormal glucose,insulin,and lipid levels.IMQ treatment also downregulated the hepatic mRNA expression of glucose transporter 2(Glut2)and silence information regulator 1(Sirt1),while upregulating glucose transporter 4(Glut4)and peroxisome proliferator-activated receptor gamma(PPARγ).Elevated serum TMAO levels were observed in both psoriatic patients and IMQ-treated mice.Additionally,liver FMO3 mRNA expression was increased in the psoriatic mouse model.In patients,TMAO levels positively correlated with Psoriasis Area and Severity Index(PASI)scores,serum triglyceride(TG),and total cholesterol(TC)levels.The intraperitoneal injection of TMAO exacerbated lipid dysregulation in IMQ-treated mice.A choline-rich diet further aggravated lipid abnormalities and liver injury in psoriatic mice,whereas DMB treatment alleviated these effects.RNA-Seq analysis demonstrated that TMAO upregulated hepatic microRNA-122(miR-122),which may suppress the expression of gremlin 2(GREM2),thus contributing to lipid metabolism disorder.Conclusion:TMAO may promote lipid metabolism dysregulation in psoriasis by modulating the hepatic miR-122/GREM2 pathway.
基金National Natural Science Foundation of China,Grant/Award Number:82174292Key Project of Jiangsu Provincial Administration of Traditional Chinese Medicine,Grant/Award Number:ZD202312+2 种基金Natural Science Foundation of Laboratory Medicine School in Chengdu Medical College,Grant/Award Number:JYZK202203Sichuan Province Science and Technology Program,Grant/Award Number:2024NSFSC0577 and 2021YFG0316Technology innovation group project of Foshan 2019,Grant/Award Number:FS0AA-KJ919-4402-0027。
文摘Background:The emerging incidence of pathogenic liver conditions is turning into a major concern for global health.Induction of pyroptosis in hepatocytes instigates cel-lular disintegration,which in turn liberates substantial quantities of pro-inflammatory intracellular substances,thereby accelerating the advancement of liver fibrosis.Consequently,directing therapeutic efforts towards inhibiting pyroptosis could po-tentially serve as an innovative approach in managing inflammation related chronic hepatic disorders.Methods:GSDMD-NT^(ki/wt)mice and Alb-cre^(ki/wt)mice were generated using CRISPR/Cas9 technology.After crossing the two strains together,we induced conditional cell death by doxycycline to construct a mouse model of liver fibrosis.We analyzed differ-entially expressed genes by RNA sequencing and explored their biological functions.The efficacy of obeticholic acid(OCA)in the treatment of liver fibrosis was assessed.Results:Doxycycline-treated GSDMD-NT^(ki/wt)×Alb-cre^(ki/wt)mice showed severe liver damage,vacuolation of hepatocytes,increased collagen fibers,and accumulation of lipid droplets.The expression of liver fibrosis related genes was greatly increased in the doxycycline-treated mouse liver compared with untreated mouse liver.RNA-sequencing showed that upregulated differentially expressed genes were involved in inflammatory responses,cell activation,and metabolic processes.Treatment with OCA alleviated the liver fibrosis,with reduced ALT and AST levels seen in the GSDMD-NT^(ki/wt)×Alb-cre^(ki/wt)mice.Conclusions:We successfully constructed a novel mouse model for liver fibrosis.This GSDMD-NT-induced fibrosis may be mediated by abnormal lipid metabolism.Our re-sults demonstrated that we successfully constructed a mouse model of liver fibrosis,and GSDMD-NT induced fibrosis by mediating lipid metabolism.
基金financially supported by the National Key Research and Development Program of China(2022YFD1301105)the earmarked fund for CARS(CARS-36)。
文摘Background The objective of this study was to evaluate the effects of dietary fatty acids(FA)saturation and lysophospholipids supplementation on growth,meat quality,oxidative stability,FA profiles,and lipid metabolism of finishing beef bulls.Thirty-two Angus bulls(initial body weight:623±22.6 kg;21±0.5 months of age)were used.The experiment was a completely randomized block design with a 2×2 factorial arrangement of treatments:2 diets with FA of different degree of unsaturation[high saturated FA diet(HSFA)vs.high unsaturated FA diet(HUFA)]combined with(0.075%,dry matter basis)and without lysophospholipids supplementation.The bulls were fed a high-concentrate diet(forage to concentrate,15:85)for 104 d including a 14-d adaptation period and a 90-d data and sample collection period.Results No interactions were observed between dietary FA and lysophospholipids supplementation for growth and meat quality parameters.A greater dietary ratio of unsaturated FA(UFA)to saturated FA(SFA)from 1:2 to 1:1 led to lower DM intake and backfat thickness,but did not affect growth performance and other carcass traits.Compared with HSFA,bulls fed HUFA had greater shear force in Longissimus thoracis(LT)muscle,but had lower intramuscular fat(IMF)content and SOD content in LT muscle.Compared with HUFA,feeding the HSFA diet up-regulated expression of ACC,FAS,PPARγ,and SCD1,but down-regulated expression of CPT1B.Compared with feeding HSFA,the HUFA diet led to greater concentrations of c9-C18:1 and other monounsaturated FA in LT muscle.Feeding HUFA also led to lower plasma concentrations of cholesterol,but there were no interactions between FA and lysophospholipids detected.Feeding lysophospholipids improved growth and feed conversion ratio and altered meat quality by increasing muscle pH_(24h),redness values(24 h),IMF content,and concentrations of C18:3,C20:5 and total polyunsaturated fatty acids.Furthermore,lysophospholipids supplementation led to lower malondialdehyde content and up-regulated the expression of ACC,FAS,and LPL in LT muscle.Conclusions Results indicated that supplementing a high-concentrate diet with lysophospholipids to beef bulls can enhance growth rate,feed efficiency,meat quality,and beneficial FA.Increasing the dietary ratio of UFA to SFA reduced DM intake and backfat thickness without compromising growth,suggesting potential improvements in feed efficiency.
基金supported by the Science and Technology Research Project of the Shandong Geriatrics Society in 2024(No.LKJGG2024W072).
文摘Background:It is widely accepted that an alteration in lipid metabolism can serve as an essential hallmark for the growth and progression of various malignancies.However,the potential of lipid metabolism genes(LMGs)and related pathways as drug targets for rectal adenocarcinoma(READ)treatment and prognostic evaluation requires further investigation.The objective of the present study was to construct a prognostic prediction model for READ based on LMGs,and to evaluate its performance.Methods:The RNA-seq FPKM data and clinical data from READ patients and normal rectal tissues were downloaded from The Cancer Genome Atlas database.The LMGs were acquired from the Molecular Signatures Database.Subsequently,LMGs associated with the prognosis of READ were screened,and these genes were used to construct a prognostic prediction model for READ patients.The model was then subjected to rigorous evaluation.Furthermore,immune infiltration and limma analyses were performed in different clusters,and pathway enrichment analyses were performed on the screened differentially expressed genes(DEGs).Results:A prognostic prediction model was constructed based on 5 LMGs(PLA2G2F,CBR1,CHKB,ETNPPL,and ARV1)to classify READ into high-and low-risk groups,with the low-risk group exhibiting a higher survival rate.Consequently,the prognostic model demonstrated notable predictive capability.A total of 139 DEGs were identified,38 of which were identified as being upregulated and 101 as being downregulated.Furthermore,a comparison of the immune microenvironment and immune pathways between the low-and high-risk groups revealed significant disparities.Conclusions:Predictive models based on 5 lipid metabolism DEGs effectively predicted the prognosis of READ patients.Moreover,these 5 LMGs have potential as molecular biomarkers and therapeutic targets for READ patients.
基金supported by General project of the Natural Science Foundation of Guangdong Province,China(2022A1515010907,2023A1515011266)National Natural Science Foundation of China(31700501)。
文摘Obesity caused by poor eating habits has become a global public health issue and harms human health.Rosmarinic acid(RA)is a natural active substance with many biological functions like antioxidant.However,the function of RA's lipid-lowering effect and mechanism are not entirely clear.This study aimed to explore the effect of RA on obesity and its action mechanism in Caenorhabditis elegans.RA not only alleviated intestinal inflammation and change the composition of unsaturated fatty acid,but also decreased fat storage and adjusted the size and quantity of fat droplets without threatening development and reproduction or affecting energy intake.In addition,RA improved the integrity of intestinal barrier function in C.elegans.RNA sequencing and quantitative reverse transcription-polymerase chain reaction(qRT-PCR)comprehensively revealed that the lipid-lowering mechanism mediated by RA might involve lipid metabolism and anti-inflammatory pathways.Among them,RA regulates lipid metabolism by reducing fat synthesis through SBP-1 and increasing fatty acidβ-oxidation via NHR-49.Furthermore,the anti-inflammatory pathway was associated with RA's enhancement of the ratio of unsaturated fatty acid and alleviation of inflammatory reactions caused by Pseudomonas aeruginosa(PAO1).Therefore,RA regulated lipid metabolism and relieved inflammation,which had the potential for dietary supplements or functional foods.
基金supported by the National Natural Science Foundation of China(No.82374510)the General Scientific Research Project of the Education Department of Zhejiang Province(No.Y202455593),China.
文摘Citrus,which has been consumed internationally for a long time,is widely used as a health food.Citrus and its active components exert significant effects on oxidative stress and lipid metabolism,which are closely associated with female reproductive health.Studies suggest that citrus-derived compounds may alleviate oxidative stress by activating signaling pathways such as nuclear factor erythroid 2-related factor 2(Nrf2)and Sirtuin 1(SIRT1),and improve lipid metabolism through the activation of pathways such as peroxisome proliferator-activated receptorα(PPARα).This review focuses on the effects of Citrus on oxidative stress and lipid metabolism,aiming to provide new insights for promoting female reproductive health;however,further work is needed to elucidate the mechanisms involved and validate the therapeutic potential of Citrus’s bioactive components in clinical settings.
基金financially supported by National Natural Science Foundation of China (32160801)China Agriculture Research System (CARS-39-12)+1 种基金Young Talent Fund of Association for Science and Technology in Shaanxi, China (2023-6-2-1)“Double-chain” project on livestock breeding (2022GDTSLD-46)
文摘Background Dysregulation of lipid metabolism and its consequences on growth performance in young ruminants have attracted attention,especially in the context of alternative feeding strategies.This study aims to elucidate the effects of milk replacer(MR)feeding on growth,lipid metabolism,colonic epithelial gene expression,colonic microbiota composition and systemic metabolism in goat kids compared to breast milk(BM)feeding,addressing a critical knowledge gap in early life nutrition.Methods Ten female goat kids were divided into 2 groups:those fed breast milk(BM group)and those fed a milk replacer(MR group).Over a period of 28 d,body weight was monitored and blood and tissue samples were collected for biochemical,transcriptomic and metabolomic analyses.Profiling of the colonial microbiota was performed using 16S rRNA gene sequencing.Intestinal microbiota transplantation(IMT)experiments in gnotobiotic mice were per-formed to validate causality.Results MR-fed pups exhibited reduced daily body-weight gain due to impaired lipid metabolism as evidenced by lower serum and liver total cholesterol(TC)and non-esterified fatty acid(NEFA)concentrations.Transcriptomic analysis of the colonic epithelium revealed upregulated genes involved in negative regulation of lipid metabolism,concomitant with microbiota shifts characterized by a decrease in Firmicutes and an increase in Actinobacteria.Specifically,genera such as Bifidobacterium and Prevotella were enriched in the MR group,while Clostridium and Fae-calibacterium were depleted.Metabolomics analyses confirmed alterations in bile acid and fatty acid metabolic path-ways.IMT experiments in mice recapitulated the metabolic phenotype observed in MR-fed goats,confirming the role of the microbiota in modulating host lipid metabolism.Conclusions Milk replacer feeding in goat kids disrupts lipid metabolism and gut microbiota dynamics,result-ing in reduced growth rates and metabolic alterations.These findings highlight the importance of early nutritional intervention on metabolic programming and suggest that modulation of the gut microbiota may be a target for improving growth and metabolic health in ruminants.This study contributes to the understanding of nutritional management strategies in livestock and their impact on animal health and productivity.
基金Supported by the Guangxi Science and Technology Major Projects,No.AA23073012the National Natural Science Foundation of China,No.32360035 and No.32060018.
文摘BACKGROUND Probiotic Acetobacter pasteurianus is used to treat diabetes,but its specific hypoglycemic substances and mechanisms remain unclear.AIM To investigate the components for lipid metabolism of A.pasteurianus and its hypoglycemic effects,providing a basis for its broader application.METHODS The lipid metabolism of A.pasteurianus under different growth conditions was analyzed using lipidomics.Neutral lipid staining in A.pasteurianus cells and the formation of lipid droplet-like structures were observed using a confocal laser scanning microscope.The neutral lipid components were also analyzed using thin layer chromato-graphy.A diabetic mouse model was established to evaluate the hypoglycemic effects of the main lipid components of A.pasteurianus and their role in repairing tissues such as the pancreas.RESULTS After comparing the effects of three culture media,namely,brain heart infusion(BHI)medium with 2%glucose,chromium-rich and zinc-rich medium,and mineral salt medium,A.pasteurianus grew well in BHI containing 2%glucose and produced the most lipids.A total of 583 lipid metabolic products was identified,with higher levels of coenzyme Q9(CoQ9),oleic acid(OA),and wax ester,but no triacylglycerol was observed.It was found that the components that affected lipid metabolism in A.pasteurianus were mainly CoQ9 and OA.They exhibited hypoglycemic effects comparable to metformin in diabetic mice,repaired damaged pancreatic tissues,and did not cause damage to the liver and spleen.CONCLUSION Under high-nutrient growth conditions,A.pasteurianus contains abundant lipid components,such as CoQ9 and OA,with good hypoglycemic effects.
基金supported by National Natural Science Foundation of China(No.22036001)。
文摘Seed germination plays a pivotal role in plant growth and undergoes many intricate biochemical changes including lipid metabolism.Nevertheless,little is known about lipid changes and distributions in different structures of soybean seeds during germination.Here,we applied mass spectrometry imaging(MSI)in conjunction with MS-based lipidomics to examine the lipid alterations in the embryo and cotyledon of soybean seeds during germination.To expand the coverage of lipid detection in soybean seeds,we used the novel techniques of matrix-assisted laser desorption/ionization(MALDI)and MALDI coupled with laser-postionization(MALDI-2).The results revealed that compared to MALDI,MALDI-2 enhanced the detected numbers and intensities of lipid species in various lipid classes,except for a few classes(e.g.,sphingomyelin and phosphatidylcholine).Lipidomic data showed that compared to the embryo,the cotyledon demonstrated slower but similar lipid changes during germination.These changes included the reduced levels of glycerolipids,phospholipids,and sterols,as well as the increased levels of lysophospholipids.Data from MALDI&MALDI-2 MSI supported and complemented these lipidomic findings.Our work highlights the significance of integrating lipid profiles and distributions to enhance our understanding of the metabolic pathways involved in seed germination.
文摘Lipid metabolism plays a pivotal role in gastric cancer(GC)progression,characterized by complex metabolic reprogramming that supports tumor growth and survival.This narrative review comprehensively examines the dysregulation of lipid metabolism-associated genes,including fatty acid synthase(FASN),ATPcitrate lyase,acetyl-CoA carboxylases,FA binding proteins,sterol regulatory element-binding proteins,and other key enzymes.These genes facilitate critical oncogenic processes by enhancing FA synthesis,modifying cellular signaling,and supporting cancer cell proliferation,migration,and therapy resistance.Metabolic adaptations observed in GC include increased de novo lipogenesis,altered enzymatic activities,and modified protein lipidation,which contribute to tumor aggressiveness.The review highlights the potential of targeting these metabolic pathways as a therapeutic strategy,demonstrating how inhibiting specific enzymes like FASN,ATP-citrate lyase,and stearoyl-CoA desaturase 1 can induce apoptosis,disrupt cancer stem cell properties,and potentially overcome treatment resistance.By elucidating the intricate interactions between lipid metabolism genes and cancer progression,this review provides insights into novel diagnostic and therapeutic approaches for managing GC.
基金Supported by the National Natural Science Foundation of China(No.82000922,No.81870647).
文摘The global prevalence of myopia is becoming increasingly severe,with epidemiological models predicting that by 2050,approximately 50%of the world’s population will be affected by myopia,and about 10%will suffer from high myopia.The incidence of high myopia is projected to increase fivefold,making it the leading cause of irreversible vision impairment.Myopia often leads to various complications and has been associated with other ocular diseases,including early-onset cataracts,age-related macular degeneration,and primary open angle glaucoma.As a result,the control and management of myopia have become ongoing and long-term research priorities.The pathogenesis of myopia involves complex multisystem interactions.Current mainstream theories focus primarily on choroidal hypoxia-induced scleral remodeling,with neurotransmitters such as acetylcholine and dopamine playing regulatory roles.However,recent studies have increasingly suggested that changes in nutritional intake,including proteins,fats,and cholesterol,may also be related to myopia development.The role of lipid metabolism in the onset and progression of myopia has gradually attracted growing attention.Therefore,this review aims to systematically elucidate the molecular mechanisms of lipid metabolism regulatory networks in axial myopia,integrating multidimensional factors to provide a theoretical foundation for precision intervention strategies.
基金supported by the National Natural Science Foundation of China(32172763,U22A20514)the National Key R&D Program of China(2022YFD130040302)+1 种基金the Hubei Provincial Key R&D Program(2023BBB040)the Hubei Important Science and Technology Project(2024BBA004).
文摘Background Porcine epidemic diarrhea virus(PEDV)infection poses a significant challenge to the swine industry,with limited effective control measures available.Poria cocos polysaccharides(PCP)is the primary active ingredient of Poria cocos,and has been demonstrated to show beneficial effects on intestinal damage in previous studies.However,its mechanism has not been fully understood.In the present study,18 seven-day-old piglets were divided into 3 groups:Control group,PEDV group,and PCP+PEDV group.After three days of adaptation,piglets in the PCP+PEDV group were orally administered 10 mg/kg body weight/d PCP from d 4 to 10.On d 8,piglets were orally administered with PEDV at the dose of 104.5 TCID50/piglet.This study aimed to investigate the potential effects of PCP on PEDVinduced intestinal injury and explored the underlying mechanisms.Results The results showed that PCP administration effectively alleviated diarrhea,reduced PEDV replication in the small intestine and colon of piglets,and significantly improved intestinal mucosal morphology.Specifically,PCP increased the villus height in both the jejunum and ileum and increased the villus height to crypt depth ratio in the ileum(P<0.05).Improved intestinal function was further evidenced by elevated plasma D-xylose levels and decreased diamine oxidase activity(P<0.05).Transcriptomic and proteomic analyses revealed that lipid metabolism is a key pathway regulated by PCP during PEDV infection.Notably,PCP significantly upregulated sphingolipid metabolism-related genes,including ectonucleotide pyrophosphatase/phosphodiesterase family member 7 and N-acylsphingosine amidohydrolase 2.Metabolomic analysis revealed that PCP primarily modulated the levels of plasmanylphosphoethanolamine,lysophosphatidylcholine,and carnitine.Additionally,PCP reversed the expression of key genes involved in fatty acid uptake,intracellular lipid transport,and fatty acid synthesis,such as fatty acid binding protein 2,fatty acid transport protein 4,apolipoprotein B,apolipoprotein C3,fatty acid synthase,long-chain fatty acyl CoA synthetase 3,lipoprotein lipase and acyl-CoA thioesterases 12(P<0.05).Conclusions These findings demonstrate that PCP mitigates PEDV-induced intestinal injury by modulating lipid metabolism and highlight its potential as a dietary supplement for enhancing anti-PEDV defenses and promoting intestinal health in piglets.
基金supported by the Project of Guangdong Provincial Nature Science Foundation(2023A151502511)Biological Breeding-National Science and Technology Major Project(2023ZD04068)the National Natural Science Foundation of China(32072814).
文摘Background Regulating the regional deposition of fat is crucial for improving the carcass characteristics of pigs.The intestine,as an important organ for lipid absorption and homeostasis maintenance,secretes various biological signals that participate in the crosstalk between the intestine and adipose tissue.Extracellular vesicles,as novel extracellular genetic factors that mediate metabolic signal exchange among multiple tissues,have emerged as a hotspot and breakthrough in revealing the mechanisms of physiological homeostasis.However,how extracellular vesicles regulate the intestinal-adipose signaling axis,especially in relation lipid metabolism and deposition is still unclear.Thus,in the current study,intestinal extracellular vesicles from Chinese fat-type piglets of Lantang and typical leantype piglets of Landrace were isolated and identified,and to reveal the regulatory mechanisms of lipid metabolism via intestinal extracellular vesicles in mediating intestinal-adipose crosstalk.Results We isolated and identified intestinal extracellular vesicles from the jejunum of 3-day-old Lantang and Landrace piglets(LT-EVs and LD-EVs)and further investigated their effects on lipid accumulation in porcine primary adipocytes.Compared to LD-EVs,LT-EVs promoted lipid deposition in porcine primary adipocytes,with intestinal-derived miRNAs playing a critical role in the crosstalk between the intestine and adipose tissue.Further analysis of extracellular vesicles-derived miRNA sequencing revealed that miR-30b-5p,enriched in LD-EVs,is involved in the regulation of lipid metabolism.Notably,the enrichment of miR-30b-5p in extracellular vesicles derived from IPEC-J2 cells also influenced lipid metabolism.Mechanistically,the targeted binding of miR-30b-5p and FMO3 may be critical for the extracellular vesicle-mediated regulation of lipid metabolism.Conclusions Our findings suggest that jejunal-derived extracellular vesicles play a critical role in regulating lipid metabolism,and the regulatory effect of extracellular vesicles from obese piglets was higher than that of lean piglets.Furthermore,the different expression of miRNAs,such as miR-30b-5p,in intestinal extracellular vesicles may be the key to determining lipid deposition phenotypes across the two pig breeds.
文摘Neuron-derived clone 77 (Nur77) is a member of the NR4A subfamily that plays critical roles in apoptosis, survival, proliferation, autophagy, angiogenesis, inflammatory responses, DNA repair, glycolipid metabolism and energy consumption. The deregulation of Nur77 signalling often relates to various serious diseases, including cancer and non-cancer diseases. A systematic review is necessary for the better understanding of Nur77 in clinical treatment. In this article, we comprehensively conclude the lipid regulation function and expression of Nur77, and its role in COPD. Finally, we prospect that development of drugs and clinical biochemical investigations targeting of Nur77 has considerable potential within healthcare.
文摘Objective To clarify the causal relationship between the level of cytoplasmic unactivated mineralocorticoid receptor(MR)and the development of tubulointerstitial nephritis(TIN),and to evaluate the impact of MR on dyslipidemia,particularly secondary hyperlipemia,in patients with diabetic kidney disease.Methods We conducted a two-sample Mendelian randomization study using genome-wide association study(GWAS)summary data.Genetic variants associated with MR levels were selected as exposures,with TIN and lipid profiles[including low-density lipoprotein cholesterol(LDL-C),triglyceride,and high-density lipoprotein cholesterol]as outcomes.A two-step Mendelian randomization approach was used to assess TIN as a mediator,employing inverse variance weighted regression as the primary analysis,supplemented by Mendelian randomization-Egger,weighted median,and sensitivity analyses.Results Cytoplasmic unactivated MR level exhibited a significant causal association with a decreased risk of TIN(OR=0.8598,95%CI[0.7775-0.9508],P<0.001).Although no significant causal relationship was identified between MR level and secondary hyperlipemia,a potential association of cytoplasmic unactivated MR level with lower LDL-C levels was observed(OR=0.9901,95%CI[0.9821-0.9983],P=0.018).Additionally,TIN exhibited causal links with secondary hyperlipemia(OR=1.0016,95%CI[1.0002-1.0029],P=0.020)and elevated LDL-C(OR=1.0111,95%CI[1.0024-1.0199],P=0.012),particularly LDL-C in European males(OR=1.0230,95%CI[1.0103-1.0358],P<0.001).Inverse Mendelian randomization analysis revealed causal relationships between TIN and genetically predicted triglyceride(OR=0.7027,95%CI[0.6189-0.7978],P<0.001),high-density lipoprotein cholesterol(OR=1.1247,95%CI[1.0019-1.2626],P=0.046),and LDL-C(OR=0.8423,95%CI[0.7220-0.9827],P=0.029).Notably,TIN mediated 16.7%of the causal association between MR and LDL-C levels.Conclusions MR plays a critical role in the development of TIN and lipid metabolism,highlighting the potential of MR-antagonists in reducing renal damage and lipid metabolism-associated complications.
基金supported by the National Natural Science Foundation of China(No.82404365)the Noncommunicable Chronic Diseases-National Science and Technology Major Project(No.2023ZD0513200)+7 种基金China Medical Board(No.15-230)China Postdoctoral Science Foundation(Nos.2023M730317and 2023T160066)the Fundamental Research Funds for the Central Universities(No.3332023042)the Open Project of Hebei Key Laboratory of Environment and Human Health(No.202301)the National Key Research and Development Program of China(No.2022YFC3703000)the Non-profit Central Research Institute Fund of Chinese Academy of Medical Sciences(No.2022-JKCS-11)the CAMS Innovation Fund for Medical Sciences(No.2022-I2M-JB-003)the Programs of the National Natural Science Foundation of China(No.21976050).
文摘Associations of per-and polyfluoroalkyl substances(PFAS)on lipid metabolism have been documented but research remains scarce regarding effect of PFAS on lipid variability.To deeply understand their relationship,a step-forward in causal inference is expected.To address these,we conducted a longitudinal study with three repeated measurements involving 201 participants in Beijing,among which 100 eligible participants were included for the present study.Twenty-three PFAS and four lipid indicators were assessed at each visit.We used linear mixed models and quantile g-computation models to investigate associations between PFAS and blood lipid levels.A latent class growth model described PFAS serum exposure patterns,and a generalized linear model demonstrated associations between these patterns and lipid variability.Our study found that PFDA was associated with increased TC(β=0.083,95%CI:0.011,0.155)and HDL-C(β=0.106,95%CI:0.034,0.178).The PFAS mixture also showed a positive relationship with TC(β=0.06,95%CI:0.02,0.10),with PFDA contributing most positively.Compared to the low trajectory group,the middle trajectory group for PFDA was associated with VIM of TC(β=0.756,95%CI:0.153,1.359).Furthermore,PFDA showed biological gradientswith lipid metabolism.This is the first repeated-measures study to identify the impact of PFAS serum exposure pattern on the lipid metabolism and the first to estimate the association between PFAS and blood lipid levels in middle-aged and elderly Chinese and reinforce the evidence of their causal relationship through epidemiological studies.
基金supported by the National Key R&D Program of China(2022YFF1100301)the Major Science and Technology Project of Henan Province(231100310200)+2 种基金Yunnan Applied Basic Research Project(202301AS070057)Yunnan Key Research and Development Projects(202305AH340005,202203AC100009,202003AD150012)Yunnan Characteristic Plant Screening and R&D Service CXO Platform(2022YKZY001)。
文摘Lipids are essential for normal life activities and biological functions of the human body,and disorders of lipid metabolism produce a lipotoxic environment,endoplasmic reticulum(ER)stress,inflammation,and cell death,which can lead to a variety of diseases in the body.It has been found that lipid metabolism disorders are closely associated with brain injury disease,cancer,metabolic disease,cardiovascular disease(CVD),respiratory disease and infectious disease.In recent years,many medicinal and edible plants such as Pueraria lobata,Gardenia jasminoides,Curcuma longa,citrus fruits,peanuts,etc.have shown great potential in regulating lipid metabolism and some of the hidden active components showed innovative mechanisms.AMPK,PPARy,SIRT1,Foxp3,NLRP3,and Keapl are increasingly recognized as therapeutic targets in the field of regulating lipid metabolism.This study aims to provide a comprehensive review of natural lipid-regulating modulators in medicinal and edible plants and their mechanism of actions,which offer valuable references for the discovery of natural lipid metabolism modulators and a therapeutic strategy for treatment of lipid metabolism-related diseases.
文摘Background:Ferroptosis is a type of regulated cell death characterized by iron-dependent lipid peroxidation,which has been linked to tumor progression and therapeutic resistance.However,the contribution of lactate metabolism and its receptor,hydroxycarboxylic acid receptor 1(HCAR1),in ferroptosis regulation in gastric cancer(GC)remains poorly understood.Focusing specifically on its effects on cell proliferation,ferroptosis regulation,and the disruption of lactate-mediatedmetabolic pathways,the study aimed to clarify the role ofHCAR1 in GC progression.Methods:Bioinformatics analysis identified prognostic genes associated with ferroptosis in GC.Receiver operating characteristic(ROC)curves were generated to assess the diagnostic potential of the predictive genes.The biological role of HCAR1 was investigated through gain and loss-of-function experiments in GC cell lines,followed by assessments of cell viability,oxidative stress indicators,gene/protein expression,and ferroptosis sensitivity under lactate stimulation or HCAR1modulation.Results:HCAR1 was significantly upregulated in GC tissues and linked to poor patient outcomes.Silencing HCAR1 inhibited GC cell growth and induced ferroptosis,as shown by increased levels of reactive oxygen species(ROS)and malondialdehyde(MDA),along with decreased expression of solute carrier family 7 member 11(SLC7A11)and glutathione peroxidase 4(GPX4).Conversely,HCAR1 overexpression or exposure to extracellular lactate inhibited ferroptosis and activated antioxidant defenses.Mechanistically,lactate activation of HCAR1 increases ATP levels,which in turn inactivates AMP-activated protein kinase(AMPK).It also upregulates stearoyl-CoA desaturase 1(SCD1)through the sterol regulatory element binding protein 1(SREBP1)signaling pathway.Blocking HCAR1 reversed these effects and restored ferroptosis sensitivity.Conclusion:HCAR1 mediates lactate-driven ferroptosis resistance in GC through the AMPK-SCD1 signaling pathway.Targeting the HCAR1-lactate axis may offer a promising strategy for overcoming metabolic adaptation and improving GC treatment outcomes.
文摘Ezrin,as a key connecting protein between the cytoskeleton and cell membrane,plays an important role in various cellular physiological processes.In recent years,people have gradually attached importance to its research in the field of glucose and lipid metabolism.Based on relevant research materials,this article elaborates the structure and function of Ezrin,and focuses on its role and potential mechanism in the diseases related to abnormal glucose and lipid metabolism,such as diabetes and its complications,to provide new ideas and theoretical basis for in-depth understanding of the regulation of glucose and lipid metabolism and the prevention and treatment of related diseases.
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.
