Synapses are key structures involved in transmitting information in the nervous system,and their functions rely on the regulation of various lipids.Lipids play important roles in synapse formation,neurotransmitter rel...Synapses are key structures involved in transmitting information in the nervous system,and their functions rely on the regulation of various lipids.Lipids play important roles in synapse formation,neurotransmitter release,and signal transmission,and dysregulation of lipid metabolism is closely associated with various neurodegenerative diseases.The complex roles of lipids in synaptic function and neurological diseases have recently garnered increasing attention,but their specific mechanisms remain to be fully understood.This review aims to explore how lipids regulate synaptic activity in the central nervous system,focusing on their roles in synapse formation,neurotransmitter release,and signal transmission.Additionally,it discusses the mechanisms by which glial cells modulate synaptic function through lipid regulation.This review shows that within the central nervous system,lipids are essential components of the cell membrane bilayer,playing critical roles in synaptic structure and function.They regulate presynaptic vesicular trafficking,postsynaptic signaling pathways,and glial-neuronal interactions.Cholesterol maintains membrane fluidity and promotes the formation of lipid rafts.Glycerophospholipids contribute to the structural integrity of synaptic membranes and are involved in the release of synaptic vesicles.Sphingolipids interact with synaptic receptors through various mechanisms to regulate their activity and are also involved in cellular processes such as inflammation and apoptosis.Fatty acids are vital for energy metabolism and the synthesis of signaling molecules.Abnormalities in lipid metabolism may lead to impairments in synaptic function,affecting information transmission between neurons and the overall health of the nervous system.Therapeutic strategies targeting lipid metabolism,particularly through cholesterol modulation,show promise for treating these conditions.In neurodegenerative diseases such as Alzheimer’s disease,Parkinson disease,and amyotrophic lateral sclerosis,dysregulation of lipid metabolism is closely linked to synaptic dysfunction.Therefore,lipids are not only key molecules in neural regeneration and synaptic repair but may also contribute to neurodegenerative pathology when metabolic dysregulation occurs.Further research is needed to elucidate the specific mechanisms linking lipid metabolism to synaptic dysfunction and to develop targeted lipid therapies for neurological diseases.展开更多
This study investigated the neuroprotective effects of lactate in subarachnoid hemorrhage,a severe cerebrovascular disease that is commonly caused by arterial aneurysm rupture and has limited early treatment options.L...This study investigated the neuroprotective effects of lactate in subarachnoid hemorrhage,a severe cerebrovascular disease that is commonly caused by arterial aneurysm rupture and has limited early treatment options.Lactate,a metabolic byproduct,has been shown to have neuroprotective properties,including enhancing cerebral microcirculation and reducing intracranial pressure in acute brain injury patients.However,the protective mechanisms of lactate in subarachnoid hemorrhage remain unknown.In this study,we showed that lactate alleviates early brain damage in subarachnoid hemorrhage by promoting neuronal lipid synthesis and the formation of lipid droplets in astrocytes.In vivo experiments using a subarachnoid hemorrhage mouse model showed that lactate treatment significantly improved neurological scores,reduced brain inflammation,and promoted lipid droplet formation in astrocytes within 24 hours.Lactate treatment increased free fatty acids levels in the brain.The results suggest that astrocytes absorbed these free fatty acids and converted them into lipid droplets,thus reducing cellular lipotoxicity.Moreover,lactate enhanced the antiapoptotic capacity of astrocytes by upregulating the expression of PLIN5,a protein crucial for lipid droplet formation.The inhibition of lipid synthesis or lipid droplet formation counteracted the neuroprotective effects of lactate,indicating that lactate’s protective role is closely linked to lipid metabolism and lipid droplet formation.In vitro experiments on HT22 neuronal cells exposed to hemin-an agent used to simulate subarachnoid hemorrhage injury-demonstrated that lactate mitigated cellular damage by reducing lipid peroxidation and preserving mitochondrial membrane potential.Lactate treatment in HT22 cells and astrocytes also showed that inhibition of lipid synthesis or lipid droplet formation reversed its protective effects,further emphasizing the importance of lipid metabolism in the neuroprotective action of lactate.This study provides insights into the neuroprotective mechanisms of lactate in subarachnoid hemorrhage.It indicates that lactate plays a role in promoting lipid synthesis in neurons and enhancing lipid droplet formation in astrocytes,thus mitigating brain damage and improving cell survival.These findings suggest that lactate,through its regulation of lipid metabolism,could be a potential therapeutic agent for subarachnoid hemorrhage.展开更多
Alzheimer’s disease is the most common cause of dementia.Although increasing evidence suggests that disruptions in lipid metabolism are closely associated with the disease,the overall profile of lipid and sterol chan...Alzheimer’s disease is the most common cause of dementia.Although increasing evidence suggests that disruptions in lipid metabolism are closely associated with the disease,the overall profile of lipid and sterol changes that occur in the brain during Alzheimer’s disease remains unclear.In this study,we compared brain tissues extracted from 32-week-old male wild-type mice and 5×FAD transgenic Alzheimer’s disease model mice,which carry mutations in the amyloid precursor protein(APP)and presenilin 1(PS1)genes.Using untargeted lipidomics and sterolomics techniques,we investigated the metabolic profiles of lipids,with a focus on sterols specifically,in three brain regions:cerebellum,hippocampus,and olfactory bulb.Our results revealed significant alterations in various lipids,particularly in the hippocampus and olfactory bulb,suggesting changes in energy levels in these regions.Further pathway analysis indicated notable disruptions in key metabolic processes,particularly those related to fatty acids and cell membrane components.Additionally,we observed decreased expression of 15 genes involved in lipid and sterol regulation.Collectively,these findings provide new insights into how imbalances in lipid and sterol metabolism may contribute to the progression of Alzheimer’s disease,highlighting potential metabolic pathways involved in the development of this debilitating disease.展开更多
Cochlear hair cell(HC)damage is a primary cause of sensorineural hearing loss.In this study,we performed metabolomic profiling of cochlear sensory epithelium following neomycin-induced HC injury and identified elevate...Cochlear hair cell(HC)damage is a primary cause of sensorineural hearing loss.In this study,we performed metabolomic profiling of cochlear sensory epithelium following neomycin-induced HC injury and identified elevated arginine metabolism as a key metabolic characteristic of damaged HCs.Using a highly sensitive and specific biosensor,we confirmed that injury induced an increase in arginine levels within cochlear HCs.By manipulating the levels of arginine and its downstream metabolites,we discovered that unmetabolized arginine exerts a strong protective effect on cochlear HCs,independent of its downstream metabolites,such as nitric oxide.Furthermore,integrated metabolomic and transcriptomic analyses revealed that arginine plays a critical role in reprogramming phospholipid metabolism.Arginine supplementation enhanced membrane phospholipid saturation through the Lands cycle and de novo lipogenesis,and protected HCs from phospholipid peroxidation-induced membrane damage and subsequent cell death.Notably,arginine supplementation protected hearing from both noise-and aminoglycoside-induced injury in mice.These findings underscore the role of unmetabolized arginine in modulating phospholipid metabolism and preventing membrane damage in cochlear HCs,highlighting that targeting phospholipid metabolism is an effective hearing protection strategy.展开更多
Growing evidence suggests that abnormal lipid metabolism occurs in amyotrophic lateral sclerosis,even in the presymptomatic stage,implying an etiologic link.However,the genetic mechanism underlying altered lipid level...Growing evidence suggests that abnormal lipid metabolism occurs in amyotrophic lateral sclerosis,even in the presymptomatic stage,implying an etiologic link.However,the genetic mechanism underlying altered lipid levels in amyotrophic lateral sclerosis remains elusive.Therefore,in this study,we performed genetic correlation analysis,a cross-trait meta-analysis,tissue-specific enrichment analysis,and bidirectional two-sample Mendelian randomization analysis of European population to explore whether there is a genetic and causal relationship between lipids and amyotrophic lateral sclerosis.The effect of lipid-lowering drugs on amyotrophic lateral sclerosis was also evaluated using a drug target Mendelian randomization approach.The results showed a positive genetic correlation between amyotrophic lateral sclerosis and both high-density lipoprotein cholesterol and apolipoprotein A1 and identified 71 independent shared loci between amyotrophic lateral sclerosis and high-density lipoprotein cholesterol,as well as 55 independent shared loci between amyotrophic lateral sclerosis and apolipoprotein A1.These shared loci were enriched in the lipid metabolic pathway and the alcohol metabolic pathway.Further Mendelian randomization analysis targeting lipid-lowering drugs showed that single nucleotide polymorphisms within the ACLY and PCSK9 genes had a protective effect against amyotrophic lateral sclerosis risk by decreasing low-density lipoprotein cholesterol.The combination of ACLY and PCSK9 inhibitors has a greater protective effect on amyotrophic lateral sclerosis risk than that of PCSK9 inhibitors alone.In summary,there is a common genetic structure between lipids and amyotrophic lateral sclerosis.Mendelian randomization analysis supports an association between elevated blood lipids and the risk of developing amyotrophic lateral sclerosis,and the use of ACLY or PCSK9 inhibitors may improve disease prognosis.展开更多
Two novel aggregation-induced emission(AIE)-active probes,TPA-H and TPA-2 F,were designed and synthesized based on a triphenylamine(TPA)core.Systematic characterization demonstrated that both probes exhibit excellent ...Two novel aggregation-induced emission(AIE)-active probes,TPA-H and TPA-2 F,were designed and synthesized based on a triphenylamine(TPA)core.Systematic characterization demonstrated that both probes exhibit excellent biocompatibility(cell viability>90%at concentrations up to 50μmol/L)and outstanding LD-targeting speci⁃ficity with minimal colocalization with other organelles such as mitochondria and lysosomes.During early differentia⁃tion of 3 T 3-L 1 adipocytes,both TPA-2 F and TPA-H clearly visualized small and nascent LDs that were difficult to be detected with BODIPY,indicating superior imaging sensitivity compared to the existing fluorescent probes for LDs.Moreover,TPA-2 F demonstrated exceptional photostability,retaining over 90%of its initial fluorescence intensity after 100 continuous laser scanning cycles,significantly outperforming TPA-H.This work not only provides two high-performance LD imaging tools but also highlights the potential of AIE luminogens(AIEgens)in organelle-specific bioimaging,offering promising avenues for early diagnosis and mechanistic research of lipid-related metabolic diseases.展开更多
Recent studies have shown that lipid metabolism is a key factor affecting anther development and male fertility.However,how plants regulating the metabolic balance of multiple lipids to ensure proper anther developmen...Recent studies have shown that lipid metabolism is a key factor affecting anther development and male fertility.However,how plants regulating the metabolic balance of multiple lipids to ensure proper anther development and male fertility remains unclear.Analyzing lipid molecules related to anther fertility and genes responsible for their biosynthesis is crucial for understanding the physiological significance of lipid metabolism in crop fertility.In this study,we compared the transcriptome and the composition and content of lipids in anthers of two upland cotton(Gossypium hirsutum) materials,Shida 98(WT) and its nearly-isogenic male sterile line Shida 98A(MS).Transcriptomics analysis identified many differentially expressed genes(DEGs) between the two materials,with the genes of the alpha-linolenic acid metabolism pathway being the most significantly associated with the male sterility phenotype.Investigations on lipids revealed that the MS anthers over-accumulated free fatty acids(FFAs),phosphatidic acid(PA),mono-and di-galactosyldiacylglycerol(MGDG and DGDG),and had a decreased content of triacylglycerol(TAG),which was closely related to the abnormal metabolism of alpha-linolenic acid(C18:3);therefore,the major lipids containing C18:3-acyl chains,such as PA,MGDG,DGDG,and TAG,are proposed to play a major role in cotton anther development.We also showed that an excessive level of MGDG and DGDG caused jasmonic acid(JA) overaccumulation in MS anthers,which in turn inhibited the expression of GhFAD3 and consequently reduced the C18:3 content,presumably via a feedback regulation mechanism,ultimately affecting plant fertility.Together,our results revealed the importance of a balanced lipid metabolism in regulating the development of cotton anther and pollen and consequently male fertility.展开更多
Introduction:Advances in HIV management have transformed HIV into a chronic condition,resulting in improved prognosis and increased survival among people living with HIV(PLWH).Traditional risk factors for metabolic dy...Introduction:Advances in HIV management have transformed HIV into a chronic condition,resulting in improved prognosis and increased survival among people living with HIV(PLWH).Traditional risk factors for metabolic dysfunction-associated steatotic liver disease(MASLD)—including dyslipidemia—are prevalent in PLWH.This systematic review and meta-analysis aim to synthesize current evidence on lipid profile disturbances as contributors to MASLD in PLWH.Methods:This systematic review and meta-analysis were conducted according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses(PRISMA)guidelines and registered in PROSPERO with registration number CRD420251054477.We searched seven databases to identify studies reporting the prevalence and characteristics of MASLD in PLWH.Meta-analysis was conducted using Review Manager 5.4.1.Mean differences(MDs)were calculated using a random-effects model.Risk of bias was assessed using the ROBINS-E tool.Results:A total of 17 studies comprising 3933 HIV-positive participants were included,among whom 1226(37%)had MASLD.Male sex was significantly associated with MASLD(OR=1.57;95%CI:1.13-2.17;p=0.007).MASLD was significantly associated with higher body mass index(BMI)(MD=3.23 kg/m^(2);p<0.00001).Lipid profile analysis revealed that MASLD patients had higher total cholesterol(MD=6.62 mg/dL;p=0.01),low density lipoprotein(LDL)(MD=3.83 mg/dL;p=0.01),triglycerides(MD=63.02 mg/dL;p<0.00001),and lower high density lipoprotein(HDL)(MD=-3.73 mg/dL;p<0.0001).Conclusion:This study demonstrates a significant difference in lipid profiles(higher total cholesterol,LDL,triglycerides,and lower HDL)among PLWH who develop MASLD,suggesting a potential metabolic signature associated with this comorbidity.展开更多
The high protein and phospholipid content of yolk granules,which are naturally occurring lipoprotein complexes,coupled with a low cholesterol level.The development and utilization of yolk granules require a detailed i...The high protein and phospholipid content of yolk granules,which are naturally occurring lipoprotein complexes,coupled with a low cholesterol level.The development and utilization of yolk granules require a detailed investigation of their nutritional composition and characteristics.This study aimed to analyze the differences in nutrient composition among yolk granules from different poultry(chicken,duck,and quail)by evaluating nutrient content,microstructure,and physicochemical properties,accompanying lipidomics techniques.The findings revealed that the water,total lipid,and ash contents of duck yolk granules(DYG)were significantly lower than those of chicken yolk granules(CYG)and quail yolk granules(QYG),while the average particle size of DYG was significantly higher than that of CYG and QYG.A total of 1146 lipids molecules were identified through lipidome analysis,with glycerophospholipids(520)being the most abundant lipid class.The contents of sphingolipids content were highest in CYG,while the contents of glycerophospholipids,glycerides and fatty acyls were higher in QYG.QYG possesses a greaterω-3 andω-6 polyunsaturated fatty acids content.Furthermore,34,19,and 51 lipid biomarker candidates were identified in CYG/DYG,CYG/QYG,and DYG/QYG,respectively.This study offers valuable insights into the nutritional properties of yolk granules from different poultry eggs.展开更多
Background Fatty liver syndrome is a prevalent metabolic disorder in transition dairy cows,characterized by excessive hepatic lipid accumulation that impairs liver function and leads to systemic metabolic disturbances...Background Fatty liver syndrome is a prevalent metabolic disorder in transition dairy cows,characterized by excessive hepatic lipid accumulation that impairs liver function and leads to systemic metabolic disturbances.Docosahexaenoic acid(DHA),a prominent n-3 polyunsaturated fatty acid(PUFA),not only exhibits anti-inflammatory and anti-oxidative properties,but also holds potential in ameliorating lipid metabolism.This study integrated in vitro bovine primary hepatocyte models and in vivo dairy cow trials to investigate the regulatory effects of DHA on hepatic lipid deposition.Results In vitro,40μmol/L DHA significantly reduced triglyceride(TAG)accumulation in steatotic hepatocytes by downregulating genes involved in fatty acid transport(FABP-1,CD36)and lipogenesis(DGAT2,FAS,SREBP-1C),while upregulating markers of lipolysis(CGI-58,ATGL)and fatty acid oxidation(ACADL,CPT1A,CPT2).Transmission electron microscopy(TEM)confirmed DHA-mediated restoration of mitochondrial ultrastructure and enhanced lipid droplet(LD)-mitochondria interactions.In vivo,dietary rumen-protected DHA(180 g/d)supplementation reduced hepatic lipid deposition,improved liver function(evidenced by decreased total bilirubin and alanine aminotransferase),reduced oxidative stress and inflammation(suppressed malondialdehyde,glutathione peroxidase,and lipopolysaccharide),coincided with relieving insulin resistance(reduced insulin and glucose,as well increased adiponectin)in dairy cows with fatty liver.These improvements may be attributed to increased expression of TOMM20 and MtCo-1,promoting mitochondrial biogenesis andβ-oxidation,along with an elevated plasma n-3/n-6 ratio.Conclusions Collectively,these findings suggest that DHA supplementation represents a promising nutritional strategy for preventing spontaneous fatty liver in transition dairy cows by enhancing hepatic lipid clearance and restoring metabolic homeostasis.展开更多
Background The decline in reproductive performance of aged hens is mainly attributed to oxidative damage in reproductive organs,hepatic lipid metabolism disorders,and intestinal microbiota dysbiosis.Glycyrrhizin(GL)ha...Background The decline in reproductive performance of aged hens is mainly attributed to oxidative damage in reproductive organs,hepatic lipid metabolism disorders,and intestinal microbiota dysbiosis.Glycyrrhizin(GL)has been proven to enhance antioxidant capacity,regulate lipid metabolism and gut microbiota in mammals,but its efficacy in hens remains unclear.Hence,this study aimed to investigate whether dietary GL supplementation improves reproductive performance in hens during the late laying stage by modulating intestinal microbiota composition,hepatic lipid metabolism and ovarian antioxidant status.Results Dietary supplementation with 100 mg/kg GL significantly improved the egg production rate,egg quality,and hatching rate in aged breeder hens(P<0.05).GL supplementation also increased the serum levels of HDLC,TP and ALB,and enhanced the antioxidant capacity in both serum and ovary(P<0.05).In addition,dietary GL elevated the serum progesterone(P4)levels by enhancing the transcription level of steroid synthesis key enzymes(CYP11A1 and 3β-HSD)in the ovary(P<0.05).Dietary GL also promoted the synthesis and transport of vitellogenin(VTG)by upregulating the VTG-Ⅱ(P<0.05)and APOV1(P=0.077)expression levels in the liver,thereby increasing the number of grade follicles and small yellow follicles.Moreover,dietary GL enhanced hepatic fatty acidβ-oxidation by upregulating PPARαand CPT-I(P<0.05),and downregulating ACC expression levels(P<0.05).In agreement,liver metabolomics analysis revealed that dietary GL supplementation significantly altered hepatic metabolism,with 389 differentially identified metabolites(P<0.05).The key metabolites(e.g.,taurocholic acid,tauroursodeoxycholic acid,nicotinuric acid,glycodeoxycholic acid(hydrate))were identified,and they were mainly functionally enriched in betaalanine metabolism nicotinate,taurine and hypotaurine metabolism(P<0.05).Finally,16S rRNA gene sequencing revealed that dietary GL reversed age-induced changes in gut microbiota composition,characterized by a significant increase in Lactobacillus abundance and a decrease in Bacteroides(P<0.05).Conclusions These results collectively demonstrate that dietary supplementation with 100 mg/kg GL improved reproductive performance by reversing age-induced changes in gut microbiota,enhancing hepatic vitellogenin synthesis,and ameliorating ovarian function in aged breeder hens.This study suggests that dietary GL is a potential strategy to improve reproductive performance in broiler breeder hens during the late laying period.展开更多
Objective:To evaluate the hepatoprotective effects of skate-derived bioactives-collagen peptides(CPs)and chondroitin-against ethanol(EtOH)-induced liver injury and to elucidate their underlying mechanisms.Methods:The ...Objective:To evaluate the hepatoprotective effects of skate-derived bioactives-collagen peptides(CPs)and chondroitin-against ethanol(EtOH)-induced liver injury and to elucidate their underlying mechanisms.Methods:The protective effects of CPs and chondroitin were assessed in different in vitro and in vivo EtOH-induced injury models.Oxidative stress was evaluated by measuring reactive oxygen species production and antioxidant markers(NRF2 and GCLC).EtOH metabolism was examined by measuring alchohol-metabolizing enzymes(alcohol dehydrogenase and aldehyde dehydrogenase)and cytochrome P450 enzymes.Furthermore,lipid dysregulation was assessed by Oil Red O staining and determination of lipogenic markers(SREBP-1 and FAS).Liver injury was also evaluated by measuring serum glutamate oxaloacetate transaminase and glutamate pyruvate transaminase,and performing histological analysis.Results:In hepatocytes and zebrafish,both CPs and chondroitin reduced oxidative stress,downregulated cytochrome P450 enzymes and lipogenic markers,and enhanced antioxidant defenses,with chondroitin showing the strongest hepatoprotection.In EtOH-fed mice,chondroitin significantly improved liver enzyme profiles,reduced hepatic lipid accumulation and inflammation,and restored antioxidant and metabolic homeostasis.Conclusions:Skate-derived chondroitin significantly attenuates EtOH-induced liver injury by modulating oxidative stress,EtOH metabolism,and lipid regulation.These findings demonstrate the hepatoprotective potential of chondroitin in different preclinical models of alcohol-induced liver damage.展开更多
Background Exosomes are crucial mediators of intercellular communication.As a key component of milk,milkderived exosomes are abundant in genetic cargo,particularly micro RNAs(mi RNAs),indicating their potential role i...Background Exosomes are crucial mediators of intercellular communication.As a key component of milk,milkderived exosomes are abundant in genetic cargo,particularly micro RNAs(mi RNAs),indicating their potential role in regulating mammary gland physiology.Therefore,this study aimed to investigate the specificity of mi RNAs in milkderived exosomes and their regulatory roles in lipid synthesis in bovine mammary epithelial cells(BMECs).Results Based on 17,838 DHI records showing a significantly higher milk fat percentage(MFP)in late lactation(4.24%±1.07%),10 high-(5.96%±0.26%,HMF)and 10 low-MFP(1.68%±0.23%,LMF)cows were selected during this stage for milk-derived exosome isolation and mi RNA profiling.Exosomes isolated via differential ultracentrifugation were verified as 50-150 nm vesicles expressing CD9,CD81,and TSG101.mi RNA sequencing identified 1,320 differentially expressed mi RNAs(496 upregulated and 824 downregulated)between the HMF_EXO and LMF_EXO groups.Uptake assays confirmed that BMECs internalized these exosomes,and q RT-PCR validation showed that mi R-423-5p and mi R-125b were significantly upregulated and downregulated in HMF_EXO-and LMF_EXO-treated BMECs,respectively.Functionally,exosomal mi R-423-5p promoted intracellular lipid accumulation and TG synthesis in BMECs by targeting APOA5,whereas mi R-125b inhibited lipolysis and fatty acid oxidation by repressing SLC27A1.Conclusions This study demonstrates that milk-derived exosomal mi RNAs represent a novel mechanism for regulating milk fat synthesis.Specifically,mi R-423-5p and mi R-125b directly modulated lipid metabolism in BMECs via the mi R-423-5p/APOA5 and mi R-125b/SLC27A1 pathways.These findings provide new insights into the molecular regulation of milk fat synthesis and highlight the importance of exosome-mediated intercellular communication in the lactating mammary gland.展开更多
Microglia,lipids,and their interaction are found to play important roles in post-stroke immunity.Microglia are sensitive to detect environment change in injured brain.Activated microglia undergo phenotypical remodelin...Microglia,lipids,and their interaction are found to play important roles in post-stroke immunity.Microglia are sensitive to detect environment change in injured brain.Activated microglia undergo phenotypical remodeling and trigger complex signal casca d es to regulate immune responses after stroke.Lipids including peripheral lipid metabolism and lipid droplet biogenesis are involved in the control of microglia functions,such as activation,phagocytosis,proliferation,and pro-inflammation.In this review,we explore new scope of microglia and lipids in immune regulation of stro ke.Implication of peripheral lipid metabolism after stroke is mentioned and advances in microglia-lipid inte raction are discussed We give a special focus on how diet and gut microbiome influence neuroinflammation system via gut-brain axis,and how these processes associate with the risk and outcome of stroke.Moreove r,we reviewed the therapeutic targets related to lipid metabolism and microglial modulation after stro ke.These can provide a prospective strategy for more efficient and safer treatment for ischemic and hemorrhagic stroke.展开更多
A key pathological feature of Parkinson’s disease(PD)is that lysosomes are overwhelmed with cellular materials that need to be degraded and cleared.While the build-up of protein is characteristic of neurodegenerative...A key pathological feature of Parkinson’s disease(PD)is that lysosomes are overwhelmed with cellular materials that need to be degraded and cleared.While the build-up of protein is characteristic of neurodegenerative diseases such as PD and Alzheimer’s disease(AD)and is thought to reflect lysosome dysfunction,lipid accumulation may also contribute to and be indicative of severe lysosomal dysfunction.Much is known about the detrimental effects of glucosylceramide accumulation in PD lysosomes.展开更多
Okara is produced in large quantities annually in China,but much of it is discarded due to its high content of indigestible dietary fiber(DF),contributing to significant environmental challenges.Recognizing the undere...Okara is produced in large quantities annually in China,but much of it is discarded due to its high content of indigestible dietary fiber(DF),contributing to significant environmental challenges.Recognizing the underexplored medicinal potential of DF,we developed an efficient fermentation method to enhance the bioavailability of okara fiber.In this study,Pediococcus acidilactici IFJ-1,which has strong enzymatic production capabilities and beneficial effects on gastrointestinal flora modulation,was selected to ferment okara.Results showed decreases in viscosity and particle size,optimized surface structure,improved thermal stability and hydration properties,and a significant increase in soluble DF content from 1.85%to 3.91%.To evaluate the physiological effects,hyperlipidemic mouse models were established and subjected to dietary interventions utilizing okara and fermented okara to measure changes in physicochemical parameters,gut microbiota composition,and lipid metabolism.The dietary intervention was effective,particularly in the fermented okara group,showing a 7.3%weight loss,improved blood lipids(triglycerides:‒39.8%,total cholesterol:‒12.8%,low-density lipoprotein cholesterol:‒34.2%,high-density lipoprotein cholesterol:+26.2%),and a 22.2%lower liver index.Gut microbiota analysis revealed that fermented okara positively modulated the microbial community by increasing the abundance of beneficial bacteria(e.g.,Bacteroidota)and reducing the abundance of obesity-associated bacteria(e.g.,Bacillota).Lipid metabolism profiling further demonstrated that fermented okara downregulated harmful lipids(e.g.,(O-acyl)-ω-hydroxy fatty acids,ceramides,and diacylglycerols)while upregulating beneficial phospholipids(e.g.,phosphatidylinositol,phosphatidylserine,phosphatidylethanolamine,lysophosphatidylinositol and lysophosphatidic acid).This study highlights a novel approach for enhancing DF utilization through fermentation,providing valuable insights into strategies for preventing obesity and metabolic diseases.展开更多
Background Low dietary energy levels can disrupt energy balance,causing metabolic disorders,particularly those involving in hepatic lipid metabolism.Betaine(BET),an important methyl donor,has demonstrated protective e...Background Low dietary energy levels can disrupt energy balance,causing metabolic disorders,particularly those involving in hepatic lipid metabolism.Betaine(BET),an important methyl donor,has demonstrated protective effects against liver diseases.However,its effects on hepatic lipid metabolism in pigs fed a low-net energy(NE)diet and the underlying mechanisms remain unclear.Thirty-two pigs(85.52±2.27 kg)were randomly assigned to four treatments:N-NE group(normal NE diet,2,475 kcal/kg NE),N-NEB group(normal NE diet+1,500 mg/kg BET,2,475 kcal/kg NE),R100-NE group(low-NE diet,2,375 kcal/kg NE),and R100-NEB group(low-NE diet+1,500 mg/kg BET,2,375 kcal/kg NE).The experiment lasted 35 d.Results There was no significant difference in growth performance among the groups(P>0.05).Reducing dietary NE levels caused liver dysfunction and increased total glyceride concentration,accompanied by lipid metabolism disorders.BET supplementation in a low-NE diet exhibited hepatoprotective roles,as evidenced by increased TP concentration and reduced ALT level in serum(P<0.05),as well as decreased fat content,adipocyte size,and total glyceride concentration in the liver(P<0.05).Meanwhile,dietary BET alleviated low-NE diet-induced hepatic lipid metabolism disorder by downregulating mRNA expressions of genes related to fatty acid transport(FABP3 and CD36)and lipogenesis(SREBP1c and FASN),while upregulating mRNA expressions involved in lipolysis(CPT1 and HSL)(P<0.05).Furthermore,dietary BET increased serum SAM concentration and the SAM/SAH ratio in pigs fed low-NE diets(P<0.05),thereby providing sufficient methyl groups through regulating the activities of enzymes participated in BET metabolism.Mechanistically,BET increased m^(6)A modification level and regulated mRNA and protein expressions of m^(6)A modified proteins including METTL3,METTL14,WTAP,YTHDF1,and ALKBH5.Correlation analysis showed a significant association between m^(6)A RNA methylation and hepatic lipid metabolism,suggesting that m^(6)A RNA methylation may play a critical role in mediating hepatic lipid metabolism.Conclusions Dietary BET supplementation in low-NE diets alleviated hepatic lipid metabolism disorders by regulating m^(6)A RNA methylation,ultimately reducing hepatic lipid accumulation in finishing pigs.展开更多
High-fat diets(HFD)disrupt lipid homeostasis,posing major public health risks.This study investigated the effect of ACA-DK,an insoluble dietary fiber derived from Antrodia camphorata,on HFD-induced dyslipidemia.We dem...High-fat diets(HFD)disrupt lipid homeostasis,posing major public health risks.This study investigated the effect of ACA-DK,an insoluble dietary fiber derived from Antrodia camphorata,on HFD-induced dyslipidemia.We demonstrate that ACA-DK effectively alleviates HFD-induced dyslipidemia in mice,counteracting metabolic disorders,aberrant blood lipids,and weight gain.Mechanistically,ACA-DK modulates triglycerides,phosphatidylcholine,and phosphatidylethanolamine via glycerophospholipid/choline/linoleic acid metabolism pathways,while rectifying gut dysbiosis through selective reduction of pro-inflammatory genera(Oscillibacter,Ruminiclostridium,Negativibacillus,Ruminococcaceae and Helicobacter).Integrated analysis identifies Ruminococcaceae and Helicobacter as key mediators of ACA-DK's lipid-regulatory effects,establishing microbiota-directed therapy as a strategy against dyslipidemia.We thus propose ACA-DK as a microbiota-directed dual-target therapy,simultaneously reprogramming host lipid metabolism and gut ecology to combat diet-induced metabolic diseases.These findings suggest that ACA-DK is a promising prebiotic dietary fiber for ameliorating HFD-induced lipid metabolic disorders,with potential for future development into functional foods or supplements.展开更多
The diseases caused by disorders in glucose and lipid metabolism have become one of the prevalent health issues,posing a serious threat to human health.Previous studies have shown that food-derived polysaccharides hav...The diseases caused by disorders in glucose and lipid metabolism have become one of the prevalent health issues,posing a serious threat to human health.Previous studies have shown that food-derived polysaccharides have a certain intervention effect on disorders in glucose and lipid metabolism.This article reviewed the structure-function relationship of food-derived polysaccharides and elucidated their role in regulating glucose and lipid metabolism.Some new evidence suggests that secondary metabolites such as short-chain fatty acids,secondary bile acids,and lipopolysaccharide act as signaling molecules,activating pathways related to glucose and lipid metabolism,alleviating oxidative stress,inhibiting inflammation in the body,and regulating the homeostasis of glucose and lipid metabolism.These results indicated that food-derived polysaccharides have a positive impact on the regulation of glucose and lipid metabolism by improving the gut microbiota environment.On the other hand,gut microbiota disturbance can affect the host’s health through the gut-liver,gut-brain and gut-adipose tissue axes.Therefore,it is speculated that food-derived polysaccharides may intervene in glucose and lipid metabolism through the inter-organ crosstalk between gut,liver,adipose tissue,and nervous system.This essay provides a theoretical basis for the development and utilization of food-derived polysaccharides as prebiotics in intervening disorders in glucose and lipid metabolism.展开更多
The high hydrophilicity of pineapple leaf fibres(PALF)limits their use in cement-and gypsum-based composites exposed to moisture.This study evaluates,for the first time,the combined effect of palm kernel oil and beesw...The high hydrophilicity of pineapple leaf fibres(PALF)limits their use in cement-and gypsum-based composites exposed to moisture.This study evaluates,for the first time,the combined effect of palm kernel oil and beeswax on the hygroscopic resistance and mechanical stability of PALF.The fibres were functionalised with three formulations(oil,wax,and a 1:2 oil/wax blend)applied at different mass ratios(CR=0.5-2).Treatments increased the average bundle diameter by up to+46%(238μm)and reduced density down to 1.06 g/cm^(3).Hygroscopically,water absorption decreased from 202.4%(raw fibres)to 76.3%(CR=2),representing a maximum reduction of 59.4%in saline medium,while moisture regain dropped from 27.9%to 14.6%(−47.7%).The oil/wax blend proved most effective,simultaneously reducing water absorption(−51.2%)and moisture regain(−46.8%)at CR=1.Mechanically,the fibres retained tensile strength(415.2 vs.460.8 MPa,+11%at CR=1)and exhibited enhanced ductility(+62.5%,with elongation at break increasing from 1.6%to 2.6%),without significantly altering Young’s modulus(12.3 to 10 GPa).Water absorption kinetics were accurately described by the Czel and Mohsenin models(R^(2)>0.98).These findings clearly demonstrate that bio-based lipid coatings can provide an eco-friendly alternative to conventional chemical treatments.They improve hygroscopic resistance and preserve mechanical integrity of PALF,providing original quantitative data for their integration into durable cement-and gypsum-based composites subjected to humid or cyclic wet-dry conditions.展开更多
基金supported by the National Natural Science Foundation of China,No.82201568(to QQ)Capital’s Funds for Health Improvement and Research,No.2024-2-1031(to QQ)Beijing Nova Program,No.20240484566(to QQ).
文摘Synapses are key structures involved in transmitting information in the nervous system,and their functions rely on the regulation of various lipids.Lipids play important roles in synapse formation,neurotransmitter release,and signal transmission,and dysregulation of lipid metabolism is closely associated with various neurodegenerative diseases.The complex roles of lipids in synaptic function and neurological diseases have recently garnered increasing attention,but their specific mechanisms remain to be fully understood.This review aims to explore how lipids regulate synaptic activity in the central nervous system,focusing on their roles in synapse formation,neurotransmitter release,and signal transmission.Additionally,it discusses the mechanisms by which glial cells modulate synaptic function through lipid regulation.This review shows that within the central nervous system,lipids are essential components of the cell membrane bilayer,playing critical roles in synaptic structure and function.They regulate presynaptic vesicular trafficking,postsynaptic signaling pathways,and glial-neuronal interactions.Cholesterol maintains membrane fluidity and promotes the formation of lipid rafts.Glycerophospholipids contribute to the structural integrity of synaptic membranes and are involved in the release of synaptic vesicles.Sphingolipids interact with synaptic receptors through various mechanisms to regulate their activity and are also involved in cellular processes such as inflammation and apoptosis.Fatty acids are vital for energy metabolism and the synthesis of signaling molecules.Abnormalities in lipid metabolism may lead to impairments in synaptic function,affecting information transmission between neurons and the overall health of the nervous system.Therapeutic strategies targeting lipid metabolism,particularly through cholesterol modulation,show promise for treating these conditions.In neurodegenerative diseases such as Alzheimer’s disease,Parkinson disease,and amyotrophic lateral sclerosis,dysregulation of lipid metabolism is closely linked to synaptic dysfunction.Therefore,lipids are not only key molecules in neural regeneration and synaptic repair but may also contribute to neurodegenerative pathology when metabolic dysregulation occurs.Further research is needed to elucidate the specific mechanisms linking lipid metabolism to synaptic dysfunction and to develop targeted lipid therapies for neurological diseases.
基金National Nature Science Foundation of China,No.81870944(to FL).
文摘This study investigated the neuroprotective effects of lactate in subarachnoid hemorrhage,a severe cerebrovascular disease that is commonly caused by arterial aneurysm rupture and has limited early treatment options.Lactate,a metabolic byproduct,has been shown to have neuroprotective properties,including enhancing cerebral microcirculation and reducing intracranial pressure in acute brain injury patients.However,the protective mechanisms of lactate in subarachnoid hemorrhage remain unknown.In this study,we showed that lactate alleviates early brain damage in subarachnoid hemorrhage by promoting neuronal lipid synthesis and the formation of lipid droplets in astrocytes.In vivo experiments using a subarachnoid hemorrhage mouse model showed that lactate treatment significantly improved neurological scores,reduced brain inflammation,and promoted lipid droplet formation in astrocytes within 24 hours.Lactate treatment increased free fatty acids levels in the brain.The results suggest that astrocytes absorbed these free fatty acids and converted them into lipid droplets,thus reducing cellular lipotoxicity.Moreover,lactate enhanced the antiapoptotic capacity of astrocytes by upregulating the expression of PLIN5,a protein crucial for lipid droplet formation.The inhibition of lipid synthesis or lipid droplet formation counteracted the neuroprotective effects of lactate,indicating that lactate’s protective role is closely linked to lipid metabolism and lipid droplet formation.In vitro experiments on HT22 neuronal cells exposed to hemin-an agent used to simulate subarachnoid hemorrhage injury-demonstrated that lactate mitigated cellular damage by reducing lipid peroxidation and preserving mitochondrial membrane potential.Lactate treatment in HT22 cells and astrocytes also showed that inhibition of lipid synthesis or lipid droplet formation reversed its protective effects,further emphasizing the importance of lipid metabolism in the neuroprotective action of lactate.This study provides insights into the neuroprotective mechanisms of lactate in subarachnoid hemorrhage.It indicates that lactate plays a role in promoting lipid synthesis in neurons and enhancing lipid droplet formation in astrocytes,thus mitigating brain damage and improving cell survival.These findings suggest that lactate,through its regulation of lipid metabolism,could be a potential therapeutic agent for subarachnoid hemorrhage.
基金supported by the National Natural Science Foundation of China,Nos.82200784,32271311Qizhen Foundation,No.226‐2023‐00008(all to LH).
文摘Alzheimer’s disease is the most common cause of dementia.Although increasing evidence suggests that disruptions in lipid metabolism are closely associated with the disease,the overall profile of lipid and sterol changes that occur in the brain during Alzheimer’s disease remains unclear.In this study,we compared brain tissues extracted from 32-week-old male wild-type mice and 5×FAD transgenic Alzheimer’s disease model mice,which carry mutations in the amyloid precursor protein(APP)and presenilin 1(PS1)genes.Using untargeted lipidomics and sterolomics techniques,we investigated the metabolic profiles of lipids,with a focus on sterols specifically,in three brain regions:cerebellum,hippocampus,and olfactory bulb.Our results revealed significant alterations in various lipids,particularly in the hippocampus and olfactory bulb,suggesting changes in energy levels in these regions.Further pathway analysis indicated notable disruptions in key metabolic processes,particularly those related to fatty acids and cell membrane components.Additionally,we observed decreased expression of 15 genes involved in lipid and sterol regulation.Collectively,these findings provide new insights into how imbalances in lipid and sterol metabolism may contribute to the progression of Alzheimer’s disease,highlighting potential metabolic pathways involved in the development of this debilitating disease.
基金supported by the National Natural Science Foundation of China(82271159,82425018,82071049,81830029,82192860,81922018,82201283,82101219,and 82192861)Shanghai Clinical Medical Research Center for Otolaryngology Diseases(20MC1920200)the STI2030-Major Projects(2022ZD0205400).
文摘Cochlear hair cell(HC)damage is a primary cause of sensorineural hearing loss.In this study,we performed metabolomic profiling of cochlear sensory epithelium following neomycin-induced HC injury and identified elevated arginine metabolism as a key metabolic characteristic of damaged HCs.Using a highly sensitive and specific biosensor,we confirmed that injury induced an increase in arginine levels within cochlear HCs.By manipulating the levels of arginine and its downstream metabolites,we discovered that unmetabolized arginine exerts a strong protective effect on cochlear HCs,independent of its downstream metabolites,such as nitric oxide.Furthermore,integrated metabolomic and transcriptomic analyses revealed that arginine plays a critical role in reprogramming phospholipid metabolism.Arginine supplementation enhanced membrane phospholipid saturation through the Lands cycle and de novo lipogenesis,and protected HCs from phospholipid peroxidation-induced membrane damage and subsequent cell death.Notably,arginine supplementation protected hearing from both noise-and aminoglycoside-induced injury in mice.These findings underscore the role of unmetabolized arginine in modulating phospholipid metabolism and preventing membrane damage in cochlear HCs,highlighting that targeting phospholipid metabolism is an effective hearing protection strategy.
基金funded by the National Natural Science Foundation of China,Nos.82401670(to KX),81873784(to DF),and 82071426(to DF)the Clinical Cohort Construction Program of Peking University Third Hospital,No.BYSYDL2019002(to DF)the Postdoctoral Fellowship Program of China Postdoctoral Science Foundation,No.GZC20230152(to KX).
文摘Growing evidence suggests that abnormal lipid metabolism occurs in amyotrophic lateral sclerosis,even in the presymptomatic stage,implying an etiologic link.However,the genetic mechanism underlying altered lipid levels in amyotrophic lateral sclerosis remains elusive.Therefore,in this study,we performed genetic correlation analysis,a cross-trait meta-analysis,tissue-specific enrichment analysis,and bidirectional two-sample Mendelian randomization analysis of European population to explore whether there is a genetic and causal relationship between lipids and amyotrophic lateral sclerosis.The effect of lipid-lowering drugs on amyotrophic lateral sclerosis was also evaluated using a drug target Mendelian randomization approach.The results showed a positive genetic correlation between amyotrophic lateral sclerosis and both high-density lipoprotein cholesterol and apolipoprotein A1 and identified 71 independent shared loci between amyotrophic lateral sclerosis and high-density lipoprotein cholesterol,as well as 55 independent shared loci between amyotrophic lateral sclerosis and apolipoprotein A1.These shared loci were enriched in the lipid metabolic pathway and the alcohol metabolic pathway.Further Mendelian randomization analysis targeting lipid-lowering drugs showed that single nucleotide polymorphisms within the ACLY and PCSK9 genes had a protective effect against amyotrophic lateral sclerosis risk by decreasing low-density lipoprotein cholesterol.The combination of ACLY and PCSK9 inhibitors has a greater protective effect on amyotrophic lateral sclerosis risk than that of PCSK9 inhibitors alone.In summary,there is a common genetic structure between lipids and amyotrophic lateral sclerosis.Mendelian randomization analysis supports an association between elevated blood lipids and the risk of developing amyotrophic lateral sclerosis,and the use of ACLY or PCSK9 inhibitors may improve disease prognosis.
文摘Two novel aggregation-induced emission(AIE)-active probes,TPA-H and TPA-2 F,were designed and synthesized based on a triphenylamine(TPA)core.Systematic characterization demonstrated that both probes exhibit excellent biocompatibility(cell viability>90%at concentrations up to 50μmol/L)and outstanding LD-targeting speci⁃ficity with minimal colocalization with other organelles such as mitochondria and lysosomes.During early differentia⁃tion of 3 T 3-L 1 adipocytes,both TPA-2 F and TPA-H clearly visualized small and nascent LDs that were difficult to be detected with BODIPY,indicating superior imaging sensitivity compared to the existing fluorescent probes for LDs.Moreover,TPA-2 F demonstrated exceptional photostability,retaining over 90%of its initial fluorescence intensity after 100 continuous laser scanning cycles,significantly outperforming TPA-H.This work not only provides two high-performance LD imaging tools but also highlights the potential of AIE luminogens(AIEgens)in organelle-specific bioimaging,offering promising avenues for early diagnosis and mechanistic research of lipid-related metabolic diseases.
基金supported by the Science and Technology Major Program of Bingtuan,China (2023AA008)the National Natural Science Foundation of China (31960369)+1 种基金the Bingtuan Science and Technology Program,China (2025DA001)the Henan Provincial Science and Technology Research Project,China (222102110200)。
文摘Recent studies have shown that lipid metabolism is a key factor affecting anther development and male fertility.However,how plants regulating the metabolic balance of multiple lipids to ensure proper anther development and male fertility remains unclear.Analyzing lipid molecules related to anther fertility and genes responsible for their biosynthesis is crucial for understanding the physiological significance of lipid metabolism in crop fertility.In this study,we compared the transcriptome and the composition and content of lipids in anthers of two upland cotton(Gossypium hirsutum) materials,Shida 98(WT) and its nearly-isogenic male sterile line Shida 98A(MS).Transcriptomics analysis identified many differentially expressed genes(DEGs) between the two materials,with the genes of the alpha-linolenic acid metabolism pathway being the most significantly associated with the male sterility phenotype.Investigations on lipids revealed that the MS anthers over-accumulated free fatty acids(FFAs),phosphatidic acid(PA),mono-and di-galactosyldiacylglycerol(MGDG and DGDG),and had a decreased content of triacylglycerol(TAG),which was closely related to the abnormal metabolism of alpha-linolenic acid(C18:3);therefore,the major lipids containing C18:3-acyl chains,such as PA,MGDG,DGDG,and TAG,are proposed to play a major role in cotton anther development.We also showed that an excessive level of MGDG and DGDG caused jasmonic acid(JA) overaccumulation in MS anthers,which in turn inhibited the expression of GhFAD3 and consequently reduced the C18:3 content,presumably via a feedback regulation mechanism,ultimately affecting plant fertility.Together,our results revealed the importance of a balanced lipid metabolism in regulating the development of cotton anther and pollen and consequently male fertility.
文摘Introduction:Advances in HIV management have transformed HIV into a chronic condition,resulting in improved prognosis and increased survival among people living with HIV(PLWH).Traditional risk factors for metabolic dysfunction-associated steatotic liver disease(MASLD)—including dyslipidemia—are prevalent in PLWH.This systematic review and meta-analysis aim to synthesize current evidence on lipid profile disturbances as contributors to MASLD in PLWH.Methods:This systematic review and meta-analysis were conducted according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses(PRISMA)guidelines and registered in PROSPERO with registration number CRD420251054477.We searched seven databases to identify studies reporting the prevalence and characteristics of MASLD in PLWH.Meta-analysis was conducted using Review Manager 5.4.1.Mean differences(MDs)were calculated using a random-effects model.Risk of bias was assessed using the ROBINS-E tool.Results:A total of 17 studies comprising 3933 HIV-positive participants were included,among whom 1226(37%)had MASLD.Male sex was significantly associated with MASLD(OR=1.57;95%CI:1.13-2.17;p=0.007).MASLD was significantly associated with higher body mass index(BMI)(MD=3.23 kg/m^(2);p<0.00001).Lipid profile analysis revealed that MASLD patients had higher total cholesterol(MD=6.62 mg/dL;p=0.01),low density lipoprotein(LDL)(MD=3.83 mg/dL;p=0.01),triglycerides(MD=63.02 mg/dL;p<0.00001),and lower high density lipoprotein(HDL)(MD=-3.73 mg/dL;p<0.0001).Conclusion:This study demonstrates a significant difference in lipid profiles(higher total cholesterol,LDL,triglycerides,and lower HDL)among PLWH who develop MASLD,suggesting a potential metabolic signature associated with this comorbidity.
基金supported by the National Natural Science Foundation of China(32072236)Sichuan Innovation Team Project of National Modern Agricultural Industry Technology System(SCCXTD-2024-25)Science and Technology Talent Innovation Fund of Chengdu(2024-YF05-01096-SN).
文摘The high protein and phospholipid content of yolk granules,which are naturally occurring lipoprotein complexes,coupled with a low cholesterol level.The development and utilization of yolk granules require a detailed investigation of their nutritional composition and characteristics.This study aimed to analyze the differences in nutrient composition among yolk granules from different poultry(chicken,duck,and quail)by evaluating nutrient content,microstructure,and physicochemical properties,accompanying lipidomics techniques.The findings revealed that the water,total lipid,and ash contents of duck yolk granules(DYG)were significantly lower than those of chicken yolk granules(CYG)and quail yolk granules(QYG),while the average particle size of DYG was significantly higher than that of CYG and QYG.A total of 1146 lipids molecules were identified through lipidome analysis,with glycerophospholipids(520)being the most abundant lipid class.The contents of sphingolipids content were highest in CYG,while the contents of glycerophospholipids,glycerides and fatty acyls were higher in QYG.QYG possesses a greaterω-3 andω-6 polyunsaturated fatty acids content.Furthermore,34,19,and 51 lipid biomarker candidates were identified in CYG/DYG,CYG/QYG,and DYG/QYG,respectively.This study offers valuable insights into the nutritional properties of yolk granules from different poultry eggs.
基金supported by the National Key R&D Program of China(No.2022YFD1301001)。
文摘Background Fatty liver syndrome is a prevalent metabolic disorder in transition dairy cows,characterized by excessive hepatic lipid accumulation that impairs liver function and leads to systemic metabolic disturbances.Docosahexaenoic acid(DHA),a prominent n-3 polyunsaturated fatty acid(PUFA),not only exhibits anti-inflammatory and anti-oxidative properties,but also holds potential in ameliorating lipid metabolism.This study integrated in vitro bovine primary hepatocyte models and in vivo dairy cow trials to investigate the regulatory effects of DHA on hepatic lipid deposition.Results In vitro,40μmol/L DHA significantly reduced triglyceride(TAG)accumulation in steatotic hepatocytes by downregulating genes involved in fatty acid transport(FABP-1,CD36)and lipogenesis(DGAT2,FAS,SREBP-1C),while upregulating markers of lipolysis(CGI-58,ATGL)and fatty acid oxidation(ACADL,CPT1A,CPT2).Transmission electron microscopy(TEM)confirmed DHA-mediated restoration of mitochondrial ultrastructure and enhanced lipid droplet(LD)-mitochondria interactions.In vivo,dietary rumen-protected DHA(180 g/d)supplementation reduced hepatic lipid deposition,improved liver function(evidenced by decreased total bilirubin and alanine aminotransferase),reduced oxidative stress and inflammation(suppressed malondialdehyde,glutathione peroxidase,and lipopolysaccharide),coincided with relieving insulin resistance(reduced insulin and glucose,as well increased adiponectin)in dairy cows with fatty liver.These improvements may be attributed to increased expression of TOMM20 and MtCo-1,promoting mitochondrial biogenesis andβ-oxidation,along with an elevated plasma n-3/n-6 ratio.Conclusions Collectively,these findings suggest that DHA supplementation represents a promising nutritional strategy for preventing spontaneous fatty liver in transition dairy cows by enhancing hepatic lipid clearance and restoring metabolic homeostasis.
基金supported and funded by the National Key Research and Development Program of China(2023YFD1300801)the Agricultural Science and Technology Innovation Program in Chinese Academy of Agricultural Sciences(ASTIP-IAS-08)。
文摘Background The decline in reproductive performance of aged hens is mainly attributed to oxidative damage in reproductive organs,hepatic lipid metabolism disorders,and intestinal microbiota dysbiosis.Glycyrrhizin(GL)has been proven to enhance antioxidant capacity,regulate lipid metabolism and gut microbiota in mammals,but its efficacy in hens remains unclear.Hence,this study aimed to investigate whether dietary GL supplementation improves reproductive performance in hens during the late laying stage by modulating intestinal microbiota composition,hepatic lipid metabolism and ovarian antioxidant status.Results Dietary supplementation with 100 mg/kg GL significantly improved the egg production rate,egg quality,and hatching rate in aged breeder hens(P<0.05).GL supplementation also increased the serum levels of HDLC,TP and ALB,and enhanced the antioxidant capacity in both serum and ovary(P<0.05).In addition,dietary GL elevated the serum progesterone(P4)levels by enhancing the transcription level of steroid synthesis key enzymes(CYP11A1 and 3β-HSD)in the ovary(P<0.05).Dietary GL also promoted the synthesis and transport of vitellogenin(VTG)by upregulating the VTG-Ⅱ(P<0.05)and APOV1(P=0.077)expression levels in the liver,thereby increasing the number of grade follicles and small yellow follicles.Moreover,dietary GL enhanced hepatic fatty acidβ-oxidation by upregulating PPARαand CPT-I(P<0.05),and downregulating ACC expression levels(P<0.05).In agreement,liver metabolomics analysis revealed that dietary GL supplementation significantly altered hepatic metabolism,with 389 differentially identified metabolites(P<0.05).The key metabolites(e.g.,taurocholic acid,tauroursodeoxycholic acid,nicotinuric acid,glycodeoxycholic acid(hydrate))were identified,and they were mainly functionally enriched in betaalanine metabolism nicotinate,taurine and hypotaurine metabolism(P<0.05).Finally,16S rRNA gene sequencing revealed that dietary GL reversed age-induced changes in gut microbiota composition,characterized by a significant increase in Lactobacillus abundance and a decrease in Bacteroides(P<0.05).Conclusions These results collectively demonstrate that dietary supplementation with 100 mg/kg GL improved reproductive performance by reversing age-induced changes in gut microbiota,enhancing hepatic vitellogenin synthesis,and ameliorating ovarian function in aged breeder hens.This study suggests that dietary GL is a potential strategy to improve reproductive performance in broiler breeder hens during the late laying period.
基金supported by the National Research Foundation of Korea grant funded by the Korean government(Grant no.:RS-2022-NR070862).
文摘Objective:To evaluate the hepatoprotective effects of skate-derived bioactives-collagen peptides(CPs)and chondroitin-against ethanol(EtOH)-induced liver injury and to elucidate their underlying mechanisms.Methods:The protective effects of CPs and chondroitin were assessed in different in vitro and in vivo EtOH-induced injury models.Oxidative stress was evaluated by measuring reactive oxygen species production and antioxidant markers(NRF2 and GCLC).EtOH metabolism was examined by measuring alchohol-metabolizing enzymes(alcohol dehydrogenase and aldehyde dehydrogenase)and cytochrome P450 enzymes.Furthermore,lipid dysregulation was assessed by Oil Red O staining and determination of lipogenic markers(SREBP-1 and FAS).Liver injury was also evaluated by measuring serum glutamate oxaloacetate transaminase and glutamate pyruvate transaminase,and performing histological analysis.Results:In hepatocytes and zebrafish,both CPs and chondroitin reduced oxidative stress,downregulated cytochrome P450 enzymes and lipogenic markers,and enhanced antioxidant defenses,with chondroitin showing the strongest hepatoprotection.In EtOH-fed mice,chondroitin significantly improved liver enzyme profiles,reduced hepatic lipid accumulation and inflammation,and restored antioxidant and metabolic homeostasis.Conclusions:Skate-derived chondroitin significantly attenuates EtOH-induced liver injury by modulating oxidative stress,EtOH metabolism,and lipid regulation.These findings demonstrate the hepatoprotective potential of chondroitin in different preclinical models of alcohol-induced liver damage.
基金supported by the National Natural Science Foundation of China(no.32372838,U22A20506)the National Key Research and Development Program of China(no.2024YFD1300104)+1 种基金the scientific and technological development program of Jilin province(YDZJ202203CGZH037)the earmarked fund for JLARS-2025-070203。
文摘Background Exosomes are crucial mediators of intercellular communication.As a key component of milk,milkderived exosomes are abundant in genetic cargo,particularly micro RNAs(mi RNAs),indicating their potential role in regulating mammary gland physiology.Therefore,this study aimed to investigate the specificity of mi RNAs in milkderived exosomes and their regulatory roles in lipid synthesis in bovine mammary epithelial cells(BMECs).Results Based on 17,838 DHI records showing a significantly higher milk fat percentage(MFP)in late lactation(4.24%±1.07%),10 high-(5.96%±0.26%,HMF)and 10 low-MFP(1.68%±0.23%,LMF)cows were selected during this stage for milk-derived exosome isolation and mi RNA profiling.Exosomes isolated via differential ultracentrifugation were verified as 50-150 nm vesicles expressing CD9,CD81,and TSG101.mi RNA sequencing identified 1,320 differentially expressed mi RNAs(496 upregulated and 824 downregulated)between the HMF_EXO and LMF_EXO groups.Uptake assays confirmed that BMECs internalized these exosomes,and q RT-PCR validation showed that mi R-423-5p and mi R-125b were significantly upregulated and downregulated in HMF_EXO-and LMF_EXO-treated BMECs,respectively.Functionally,exosomal mi R-423-5p promoted intracellular lipid accumulation and TG synthesis in BMECs by targeting APOA5,whereas mi R-125b inhibited lipolysis and fatty acid oxidation by repressing SLC27A1.Conclusions This study demonstrates that milk-derived exosomal mi RNAs represent a novel mechanism for regulating milk fat synthesis.Specifically,mi R-423-5p and mi R-125b directly modulated lipid metabolism in BMECs via the mi R-423-5p/APOA5 and mi R-125b/SLC27A1 pathways.These findings provide new insights into the molecular regulation of milk fat synthesis and highlight the importance of exosome-mediated intercellular communication in the lactating mammary gland.
基金Shanghai Municipal Health Commission,No.20224Z0008(to PY)the National Natural Science Foundation of China,No.82101412(to MZ)+1 种基金the Science Foundation of Naval Medical Center of PLA,No.23M2702(to MZ)National Key Research and Development Program of China,No.2023YFC2506506(QL)。
文摘Microglia,lipids,and their interaction are found to play important roles in post-stroke immunity.Microglia are sensitive to detect environment change in injured brain.Activated microglia undergo phenotypical remodeling and trigger complex signal casca d es to regulate immune responses after stroke.Lipids including peripheral lipid metabolism and lipid droplet biogenesis are involved in the control of microglia functions,such as activation,phagocytosis,proliferation,and pro-inflammation.In this review,we explore new scope of microglia and lipids in immune regulation of stro ke.Implication of peripheral lipid metabolism after stroke is mentioned and advances in microglia-lipid inte raction are discussed We give a special focus on how diet and gut microbiome influence neuroinflammation system via gut-brain axis,and how these processes associate with the risk and outcome of stroke.Moreove r,we reviewed the therapeutic targets related to lipid metabolism and microglial modulation after stro ke.These can provide a prospective strategy for more efficient and safer treatment for ischemic and hemorrhagic stroke.
文摘A key pathological feature of Parkinson’s disease(PD)is that lysosomes are overwhelmed with cellular materials that need to be degraded and cleared.While the build-up of protein is characteristic of neurodegenerative diseases such as PD and Alzheimer’s disease(AD)and is thought to reflect lysosome dysfunction,lipid accumulation may also contribute to and be indicative of severe lysosomal dysfunction.Much is known about the detrimental effects of glucosylceramide accumulation in PD lysosomes.
基金supported by the Key Special Projects of the Ministry of Science and Technology(SQ2020YFF0404523)the North Anhui Soybean Advantageous Characteristic Industry Cluster Project(2023CYJQ013)+2 种基金the National Natural Science Foundation of China(32172162)the Key Genetic Technologies Research and Development Program of Hefei(2021GJ075)the Young Talents Program of Anhui Academy of Agricultural Science(QNYC-202122).
文摘Okara is produced in large quantities annually in China,but much of it is discarded due to its high content of indigestible dietary fiber(DF),contributing to significant environmental challenges.Recognizing the underexplored medicinal potential of DF,we developed an efficient fermentation method to enhance the bioavailability of okara fiber.In this study,Pediococcus acidilactici IFJ-1,which has strong enzymatic production capabilities and beneficial effects on gastrointestinal flora modulation,was selected to ferment okara.Results showed decreases in viscosity and particle size,optimized surface structure,improved thermal stability and hydration properties,and a significant increase in soluble DF content from 1.85%to 3.91%.To evaluate the physiological effects,hyperlipidemic mouse models were established and subjected to dietary interventions utilizing okara and fermented okara to measure changes in physicochemical parameters,gut microbiota composition,and lipid metabolism.The dietary intervention was effective,particularly in the fermented okara group,showing a 7.3%weight loss,improved blood lipids(triglycerides:‒39.8%,total cholesterol:‒12.8%,low-density lipoprotein cholesterol:‒34.2%,high-density lipoprotein cholesterol:+26.2%),and a 22.2%lower liver index.Gut microbiota analysis revealed that fermented okara positively modulated the microbial community by increasing the abundance of beneficial bacteria(e.g.,Bacteroidota)and reducing the abundance of obesity-associated bacteria(e.g.,Bacillota).Lipid metabolism profiling further demonstrated that fermented okara downregulated harmful lipids(e.g.,(O-acyl)-ω-hydroxy fatty acids,ceramides,and diacylglycerols)while upregulating beneficial phospholipids(e.g.,phosphatidylinositol,phosphatidylserine,phosphatidylethanolamine,lysophosphatidylinositol and lysophosphatidic acid).This study highlights a novel approach for enhancing DF utilization through fermentation,providing valuable insights into strategies for preventing obesity and metabolic diseases.
基金supported by the National Key Research and Development Program of China(2022YFD1300502)Sichuan Science and Technology Program(2021ZDZX0009)。
文摘Background Low dietary energy levels can disrupt energy balance,causing metabolic disorders,particularly those involving in hepatic lipid metabolism.Betaine(BET),an important methyl donor,has demonstrated protective effects against liver diseases.However,its effects on hepatic lipid metabolism in pigs fed a low-net energy(NE)diet and the underlying mechanisms remain unclear.Thirty-two pigs(85.52±2.27 kg)were randomly assigned to four treatments:N-NE group(normal NE diet,2,475 kcal/kg NE),N-NEB group(normal NE diet+1,500 mg/kg BET,2,475 kcal/kg NE),R100-NE group(low-NE diet,2,375 kcal/kg NE),and R100-NEB group(low-NE diet+1,500 mg/kg BET,2,375 kcal/kg NE).The experiment lasted 35 d.Results There was no significant difference in growth performance among the groups(P>0.05).Reducing dietary NE levels caused liver dysfunction and increased total glyceride concentration,accompanied by lipid metabolism disorders.BET supplementation in a low-NE diet exhibited hepatoprotective roles,as evidenced by increased TP concentration and reduced ALT level in serum(P<0.05),as well as decreased fat content,adipocyte size,and total glyceride concentration in the liver(P<0.05).Meanwhile,dietary BET alleviated low-NE diet-induced hepatic lipid metabolism disorder by downregulating mRNA expressions of genes related to fatty acid transport(FABP3 and CD36)and lipogenesis(SREBP1c and FASN),while upregulating mRNA expressions involved in lipolysis(CPT1 and HSL)(P<0.05).Furthermore,dietary BET increased serum SAM concentration and the SAM/SAH ratio in pigs fed low-NE diets(P<0.05),thereby providing sufficient methyl groups through regulating the activities of enzymes participated in BET metabolism.Mechanistically,BET increased m^(6)A modification level and regulated mRNA and protein expressions of m^(6)A modified proteins including METTL3,METTL14,WTAP,YTHDF1,and ALKBH5.Correlation analysis showed a significant association between m^(6)A RNA methylation and hepatic lipid metabolism,suggesting that m^(6)A RNA methylation may play a critical role in mediating hepatic lipid metabolism.Conclusions Dietary BET supplementation in low-NE diets alleviated hepatic lipid metabolism disorders by regulating m^(6)A RNA methylation,ultimately reducing hepatic lipid accumulation in finishing pigs.
基金supported by the National Science Fund for Distinguished Young Scholars(32025029)the Natural Science Foundation of China(32272364)Shanghai Engineering Research Center of food microbiology program(19DZ2281100).
文摘High-fat diets(HFD)disrupt lipid homeostasis,posing major public health risks.This study investigated the effect of ACA-DK,an insoluble dietary fiber derived from Antrodia camphorata,on HFD-induced dyslipidemia.We demonstrate that ACA-DK effectively alleviates HFD-induced dyslipidemia in mice,counteracting metabolic disorders,aberrant blood lipids,and weight gain.Mechanistically,ACA-DK modulates triglycerides,phosphatidylcholine,and phosphatidylethanolamine via glycerophospholipid/choline/linoleic acid metabolism pathways,while rectifying gut dysbiosis through selective reduction of pro-inflammatory genera(Oscillibacter,Ruminiclostridium,Negativibacillus,Ruminococcaceae and Helicobacter).Integrated analysis identifies Ruminococcaceae and Helicobacter as key mediators of ACA-DK's lipid-regulatory effects,establishing microbiota-directed therapy as a strategy against dyslipidemia.We thus propose ACA-DK as a microbiota-directed dual-target therapy,simultaneously reprogramming host lipid metabolism and gut ecology to combat diet-induced metabolic diseases.These findings suggest that ACA-DK is a promising prebiotic dietary fiber for ameliorating HFD-induced lipid metabolic disorders,with potential for future development into functional foods or supplements.
基金supported by the University Innovation Team of Shandong Province(2022KJ243)the National Natural Science Foundation of China(31901644)Natural Science Foundation of Shandong Province(ZR2025MS284).
文摘The diseases caused by disorders in glucose and lipid metabolism have become one of the prevalent health issues,posing a serious threat to human health.Previous studies have shown that food-derived polysaccharides have a certain intervention effect on disorders in glucose and lipid metabolism.This article reviewed the structure-function relationship of food-derived polysaccharides and elucidated their role in regulating glucose and lipid metabolism.Some new evidence suggests that secondary metabolites such as short-chain fatty acids,secondary bile acids,and lipopolysaccharide act as signaling molecules,activating pathways related to glucose and lipid metabolism,alleviating oxidative stress,inhibiting inflammation in the body,and regulating the homeostasis of glucose and lipid metabolism.These results indicated that food-derived polysaccharides have a positive impact on the regulation of glucose and lipid metabolism by improving the gut microbiota environment.On the other hand,gut microbiota disturbance can affect the host’s health through the gut-liver,gut-brain and gut-adipose tissue axes.Therefore,it is speculated that food-derived polysaccharides may intervene in glucose and lipid metabolism through the inter-organ crosstalk between gut,liver,adipose tissue,and nervous system.This essay provides a theoretical basis for the development and utilization of food-derived polysaccharides as prebiotics in intervening disorders in glucose and lipid metabolism.
文摘The high hydrophilicity of pineapple leaf fibres(PALF)limits their use in cement-and gypsum-based composites exposed to moisture.This study evaluates,for the first time,the combined effect of palm kernel oil and beeswax on the hygroscopic resistance and mechanical stability of PALF.The fibres were functionalised with three formulations(oil,wax,and a 1:2 oil/wax blend)applied at different mass ratios(CR=0.5-2).Treatments increased the average bundle diameter by up to+46%(238μm)and reduced density down to 1.06 g/cm^(3).Hygroscopically,water absorption decreased from 202.4%(raw fibres)to 76.3%(CR=2),representing a maximum reduction of 59.4%in saline medium,while moisture regain dropped from 27.9%to 14.6%(−47.7%).The oil/wax blend proved most effective,simultaneously reducing water absorption(−51.2%)and moisture regain(−46.8%)at CR=1.Mechanically,the fibres retained tensile strength(415.2 vs.460.8 MPa,+11%at CR=1)and exhibited enhanced ductility(+62.5%,with elongation at break increasing from 1.6%to 2.6%),without significantly altering Young’s modulus(12.3 to 10 GPa).Water absorption kinetics were accurately described by the Czel and Mohsenin models(R^(2)>0.98).These findings clearly demonstrate that bio-based lipid coatings can provide an eco-friendly alternative to conventional chemical treatments.They improve hygroscopic resistance and preserve mechanical integrity of PALF,providing original quantitative data for their integration into durable cement-and gypsum-based composites subjected to humid or cyclic wet-dry conditions.
