Lipid droplets serve as primary storage organelles for neutral lipids in neurons,glial cells,and other cells in the nervous system.Lipid droplet formation begins with the synthesis of neutral lipids in the endoplasmic...Lipid droplets serve as primary storage organelles for neutral lipids in neurons,glial cells,and other cells in the nervous system.Lipid droplet formation begins with the synthesis of neutral lipids in the endoplasmic reticulum.Previously,lipid droplets were recognized for their role in maintaining lipid metabolism and energy homeostasis;however,recent research has shown that lipid droplets are highly adaptive organelles with diverse functions in the nervous system.In addition to their role in regulating cell metabolism,lipid droplets play a protective role in various cellular stress responses.Furthermore,lipid droplets exhibit specific functions in neurons and glial cells.Dysregulation of lipid droplet formation leads to cellular dysfunction,metabolic abnormalities,and nervous system diseases.This review aims to provide an overview of the role of lipid droplets in the nervous system,covering topics such as biogenesis,cellular specificity,and functions.Additionally,it will explore the association between lipid droplets and neurodegenerative disorders.Understanding the involvement of lipid droplets in cell metabolic homeostasis related to the nervous system is crucial to determine the underlying causes and in exploring potential therapeutic approaches for these diseases.展开更多
When mammals are exposed to cold,their metabolism undergoes substantial changes.The liver plays a central role in maintaining energy homeostasis by shifting from glucose metabolism to lipid catabolism.A recent study b...When mammals are exposed to cold,their metabolism undergoes substantial changes.The liver plays a central role in maintaining energy homeostasis by shifting from glucose metabolism to lipid catabolism.A recent study by Davidson et al.^([1]),published in Cell Metabolism,highlights a novel mechanism involving lysosomal lipid remodeling during cold adaptation.Specifically,the study reveals that cold exposure elevates hepatic levels of Bis(Monoacylglycerol)Phosphate(BMP)lipids,which are regulated by Transcription Factor EB(TFEB)and Phospholipase A2 group XV(PLA2G15).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
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
BACKGROUND Dyslipidemia was strongly linked to stroke,however the relationship between dyslipidemia and its components and ischemic stroke remained unexplained.AIM To investigate the link between longitudinal changes ...BACKGROUND Dyslipidemia was strongly linked to stroke,however the relationship between dyslipidemia and its components and ischemic stroke remained unexplained.AIM To investigate the link between longitudinal changes in lipid profiles and dyslipidemia and ischemic stroke in a hypertensive population.METHODS Between 2013 and 2014,6094 hypertension individuals were included in this,and ischemic stroke cases were documented to the end of 2018.Longitudinal changes of lipid were stratified into four groups:(1)Normal was transformed into normal group;(2)Abnormal was transformed into normal group;(3)Normal was transformed into abnormal group;and(4)Abnormal was transformed into abnormal group.To examine the link between longitudinal changes in dyslipidemia along with its components and the risk of ischemic stroke,we utilized multivariate Cox proportional hazards models with hazard ratio(HR)and 95%CI.RESULTS The average age of the participants was 62.32 years±13.00 years,with 329 women making up 54.0%of the sample.Over the course of a mean follow-up of 4.8 years,143 ischemic strokes happened.When normal was transformed into normal group was used as a reference,after full adjustments,the HR for dyslipidemia and ischemic stroke among abnormal was transformed into normal group,normal was transformed into abnormal group and abnormal was transformed into abnormal Wei CC et al.Dyslipidemia changed and ischemic stroke WJCC https://www.wjgnet.com 2 February 6,2025 Volume 13 Issue 4 group were 1.089(95%CI:0.598-1.982;P=0.779),2.369(95%CI:1.424-3.941;P<0.001)and 1.448(95%CI:1.002-2.298;P=0.047)(P for trend was 0.233),respectively.CONCLUSION In individuals with hypertension,longitudinal shifts from normal to abnormal in dyslipidemia-particularly in total and low-density lipoprotein cholesterol-were significantly associated with the risk of ischemic stroke.展开更多
Ferroptosis is a new regulated cell death process executed by lipid peroxidation(LPO)of polyunsaturated fatty acids.Lipid droplets(LDs),as an important organelle for lipid storage and metabolism,are probably a major s...Ferroptosis is a new regulated cell death process executed by lipid peroxidation(LPO)of polyunsaturated fatty acids.Lipid droplets(LDs),as an important organelle for lipid storage and metabolism,are probably a major site of LPO and play critical roles in the regulation of ferroptosis.However,the detailed study on LPO in LDs has not been carried out because of the lack of LD-targeting tools for the in situ monitoring of LPO.Herein,the first LD-targeting LPO fluorescence probe(LD-LPO)has been developed.LD-LPO exhibits a rapid and selective fluorescence enhancement at 518 nm,which is unaffected by highly destructive reactive oxygen species(e.g.,hydroxyl radical)and environmental factor changes(e.g.,polarity and viscosity).LD-LPO is capable of targeting LDs and visualizing LPO within LDs in situ during erastin-or(1S,3R)-RSL3(RSL3)-induced ferroptosis.Moreover,LD-LPO has also been used to image LPO in the ferroptosis-associated non-alcoholic fatty liver disease(NAFLD),and to evaluate the medicine treatment of NAFLD with saroglitazar,demonstrating its utility for monitoring LPO levels in biosystems.The favorable analytical and imaging performance of LD-LPO may allow its application in more ferroptosisassociated physiological and pathological processes.展开更多
BACKGROUND Metabolic dysfunction-associated steatotic liver disease(MASLD)has emerged as a prominent and pervasive global health challenge.Bicuculline(BIC),which is a key active component of the anti-MASLD prescriptio...BACKGROUND Metabolic dysfunction-associated steatotic liver disease(MASLD)has emerged as a prominent and pervasive global health challenge.Bicuculline(BIC),which is a key active component of the anti-MASLD prescription"Eight Zhes Decoction",has been preliminarily shown by our research team to have significant potential in treating MASLD.AIM To determine BIC's efficacy in treating MASLD by regulating lipid metabolism and suppressing hepatic inflammation via nuclear factor-kappa B(NF-κB)pathway,identifying it as a therapeutic candidate.METHODS This study explored the potential of BIC in preventing and treating MASLD using zebrafish,cellular(HepG2 and AML12),and mouse models.RESULTS Our results indicate that BIC significantly reduces lipid accumulation and inflammation both in vivo and in vitro.Transcriptomic analysis suggested that the anti-MASLD effects of BIC are linked to the inhibition of the NF-κB pathway,which plays a critical role in mitigating inflammation and lipid deposition.CONCLUSION This study is the first to demonstrate that BIC specifically alleviates lipid accumulation and hepatic steatosis in MASLD models via the NF-κB signaling pathway.Overall,BIC has emerged as a promising candidate for treating MASLD.展开更多
Fucoxanthin,a kind of exclusively algae-derived carotenoids,could reduce lipid content and regulate gut microbiota composition in obese mice,showing potential in preventing hyperlipidemia.This study aimed to illustrat...Fucoxanthin,a kind of exclusively algae-derived carotenoids,could reduce lipid content and regulate gut microbiota composition in obese mice,showing potential in preventing hyperlipidemia.This study aimed to illustrate fucoxanthin efficacy in modulating lipid metabolism in serum and liver of high-fat-induced hyperlipidemia mice,as well as investigate the underlying association with gut microbiota changes.Results showed that fucoxanthin significantly reduced body weight gain and body white fat of the mice.In the serum,total triglycerides(TG),total cholesterol(TC)contents were significantly decreased and high-densitylipoprotein cholesterol levels was significantly upregulated.Moreover,fucoxanthin remarkedly prevented lipid accumulation in the liver.Especially,metabolomics results showed that lipids and lipid-like molecules were significantly downregulated compared with the control,indicating the advance of hepatic lipid metabolism.Bile acids profile in the liver was also greatly changed by fucoxanthin.Meanwhile,fucoxanthin remodeled gut microbiota composition and promoted the relative abundance of Desulfovibrio,Blautia and Clostridia genera.Finally,correlation analysis revealed that these gut microbiota changes were closely related with hepatic metabolites/metabolism and serum lipids.Altogether,this study showed great potential of fucoxanthin in improving serum lipids profile,hepatic lipids and bile acids metabolism of hyperlipidemia mice,which was associated with gut microbiota alteration.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
Objective Lipid oxidation is involved in the pathogenesis of atherosclerosis and may be contribute to the development of Ischemic stroke(IS).However,the lipid profiles associated with IS have been poorly studied.We co...Objective Lipid oxidation is involved in the pathogenesis of atherosclerosis and may be contribute to the development of Ischemic stroke(IS).However,the lipid profiles associated with IS have been poorly studied.We conducted a pilot study to identify potential IS-related lipid molecules and pathways using lipidomic profiling.Methods Serum lipidomic profiling was performed using LC-MS in 20 patients with IS and 20 age-and sex-matched healthy controls.Univariate and multivariate analyses were simultaneously performed to identify the differential lipids.Multiple testing was controlled for using a false discovery rate(FDR)approach.Enrichment analysis was performed using MetaboAnalyst software.Results Based on the 294 lipids assayed,principal component analysis(PCA)and orthogonal partial least squares discriminant analysis(OPLS-DA)models were used to distinguish patients with IS from healthy controls.Fifty-six differential lipids were identified with an FDR-adjusted P less than 0.05 and variable influences in projection(VIP)greater than 1.0.These lipids were significantly enriched in glycerophospholipid metabolism(FDR-adjusted P=0.009,impact score=0.216).Conclusions Serum lipid profiles differed significantly between patients with IS and healthy controls.Thus,glycerophospholipid metabolism may be involved in the development of IS.These results provide initial evidence that lipid molecules and their related metabolites may serve as new biomarkers and potential therapeutic targets for IS.展开更多
Dyslipidemia,a complex disorder characterized by systemic lipid profile abnormalities,affects more than half of adults globally and constitutes a major modifiable risk factor for atherosclerotic cardiovascular disease...Dyslipidemia,a complex disorder characterized by systemic lipid profile abnormalities,affects more than half of adults globally and constitutes a major modifiable risk factor for atherosclerotic cardiovascular disease.Mounting evidence has established the gut microbiota(GM)as a pivotal metabolic modulator that is correlated with atherogenic lipid profiles through dietary biotransformation,immunometabolic regulation,and bioactive metabolite signaling.However,the host-microbe interactions that drive dyslipidemia pathogenesis involve complex gene-environment crosstalk spanning epigenetic modifications to circadian entrainment.Mechanistically,GM perturbations disrupt lipid homeostasis via lipopolysaccharide-triggered hepatic very low-density lipoprotein overproduction,short-chain fatty acid-G protein-coupled receptor 43/41-mediated adipocyte lipolysis,bile acid-farnesoid X receptor/Takeda G proteincoupled receptor 5 axis dysfunction altering cholesterol flux,microbialβ-oxidation intermediates impairing mitochondrial energetics,and host-microbiota noncoding RNA crosstalk regulating lipogenic genes.This comprehensive review systematically examines three critical dimensions,including bidirectional GMlipid axis interactions,molecular cascades bridging microbial ecology to metabolic dysfunction,and translational applications of GM modulation through precision probiotics,structure-specific prebiotics,and a metabolically optimized fecal microbiota transplantation protocol.Notwithstanding these advances,critical gaps persist in establishing causal microbial taxa-pathway relationships and optimal intervention timing.Future directions require longitudinal multi-omic studies,gnotobiotic models for mechanistic validation,and machine learning-driven personalized microbiota profiling.This synthesis provides a framework for developing microbiotacentric strategies targeting dyslipidemia pathophysiology,with implications for precision dyslipidemia management and next-generation cardiovascular disease prevention.展开更多
As more and more studies have shown that lipid molecules play an important role in the whole biology,in-depth analysis of lipid structure has become particularly important in lipidomics.Mass spectrometry(MS),as the pr...As more and more studies have shown that lipid molecules play an important role in the whole biology,in-depth analysis of lipid structure has become particularly important in lipidomics.Mass spectrometry(MS),as the preferred tool for lipid analysis,has greatly promoted the development of this field.However,the existing MS methods still face many difficulties in the in-depth or even comprehensive analysis of lipid structure.In this review,we discuss recent advances in MS methods based on double bond-specific chemistries for the resolving of C=C location and geometry isomers of lipids.This progress has greatly advanced the lipidomics analysis to a deeper structural level and facilitated the development of structural lipid biology.展开更多
Ferroptosis,a type of programmed cell death,represents a distinct paradigm in cell biology.It is characterized by the iron-dependent accumulation of reactive oxygen species,which induce lipid peroxidation(LPO),and is ...Ferroptosis,a type of programmed cell death,represents a distinct paradigm in cell biology.It is characterized by the iron-dependent accumulation of reactive oxygen species,which induce lipid peroxidation(LPO),and is orchestrated by the interplay between iron,lipid peroxides,and glutathione.In this review,we emphasize the frequently overlooked role of iron in LPO beyond the classical iron-driven Fenton reaction in several crucial processes that regulate cellular iron homeostasis,including iron intake and export as well as ferritinophagy,and the emerging roles of endoplasmic reticulum-resident flavoprotein oxidoreductases,especially P450 oxidoreductases,in modulating LPO.We summarize how various types of fatty acids(FAs),including saturated,monounsaturated,and polyunsaturated FAs,differentially influence ferroptosis when incorporated into phospholipids.Furthermore,we highlight the therapeutic potential of targeting LPO to mitigate ferroptosis and discuss the regulatory mechanisms of endogenous lipophilic radical-trapping antioxidants that confer resistance to ferroptosis,shedding light on therapeutic avenues for ferroptosis-associated diseases.展开更多
Specialized pro-resolving lipid mediators including maresin 1 mediate resolution but the levels of these are reduced in Alzheimer's disease brain, suggesting that they constitute a novel target for the treatment o...Specialized pro-resolving lipid mediators including maresin 1 mediate resolution but the levels of these are reduced in Alzheimer's disease brain, suggesting that they constitute a novel target for the treatment of Alzheimer's disease to prevent/stop inflammation and combat disease pathology. Therefore, it is important to clarify whether they counteract the expression of genes and proteins induced by amyloid-β. With this objective, we analyzed the relevance of human monocyte–derived microglia for in vitro modeling of neuroinflammation and its resolution in the context of Alzheimer's disease and investigated the pro-resolving bioactivity of maresin 1 on amyloid-β42–induced Alzheimer's disease–like inflammation. Analysis of RNA-sequencing data and secreted proteins in supernatants from the monocyte-derived microglia showed that the monocyte-derived microglia resembled Alzheimer's disease–like neuroinflammation in human brain microglia after incubation with amyloid-β42. Maresin 1 restored homeostasis by down-regulating inflammatory pathway related gene expression induced by amyloid-β42 in monocyte-derived microglia, protection of maresin 1 against the effects of amyloid-β42 is mediated by a re-balancing of inflammatory transcriptional networks in which modulation of gene transcription in the nuclear factor-kappa B pathway plays a major part. We pinpointed molecular targets that are associated with both neuroinflammation in Alzheimer's disease and therapeutic targets by maresin 1. In conclusion, monocyte-derived microglia represent a relevant in vitro microglial model for studies on Alzheimer's disease-like inflammation and drug response for individual patients. Maresin 1 ameliorates amyloid-β42–induced changes in several genes of importance in Alzheimer's disease, highlighting its potential as a therapeutic target for Alzheimer's disease.展开更多
BACKGROUND Colorectal cancer(CRC)is a prevalent malignant neoplasm characterized by subtle early manifestations.AIM To investigate the correlation among serum lipid profiles,the triglyceride-glucose(TyG)index,and the ...BACKGROUND Colorectal cancer(CRC)is a prevalent malignant neoplasm characterized by subtle early manifestations.AIM To investigate the correlation among serum lipid profiles,the triglyceride-glucose(TyG)index,and the atherosclerotic index(AI)in patients with CRC.Furthermore,it explored the clinical diagnostic utility of combining serum lipids with cancer antigens in the context of CRC.METHODS A retrospective analysis encompassed 277 patients with CRC and 1034 healthy individuals.RESULTS Following propensity score matching,patients with CRC exhibited significantly reduced levels of serum triglyceride(TG),total cholesterol(TC),high-density lipoprotein cholesterol,and low-density lipoprotein cholesterol(LDL-C),as well as a diminished TyG index.Conversely,they displayed elevated AI levels compared to their healthy counterparts.Patients in advanced stages exhibited lower serum levels of TG,TC,and LDL-C compared to those in early stages.Patients with positive lymph node metastasis demonstrated reduced levels of TG,LDL-C,and the TyG index.Receiver operating characteristic analysis revealed that the combination of the TyG index,carcinoembryonic antigen,and carbohydrate antigen 19-9 yielded the highest positive prediction rate for CRC at 75.3%.CONCLUSION Preoperative serum lipid profiles exhibit a robust association with patients with CRC.The concurrent assessment of multiple serum lipids and cancer antigens effectively enhances the diagnostic accuracy for CRC.展开更多
Objective To characterize transmembrane protein 68(TMEM68)in an alternative triacylglycerol(TAG)biosynthesis pathway,and determine the interplay between TMEM68 and the canonical TAG synthesis enzyme acyl-CoA:diacylgly...Objective To characterize transmembrane protein 68(TMEM68)in an alternative triacylglycerol(TAG)biosynthesis pathway,and determine the interplay between TMEM68 and the canonical TAG synthesis enzyme acyl-CoA:diacylglycerol acyltransferase(DGAT).Methods Effects of exogenous fatty acid and monoacylglycerol on TAG synthesis and lipid droplet(LD)formation in TMEM68 overexpression and knockout cells treated with DGAT inhibitor or not were investigated by comparing LD morphology,Oil Red O staining,and measurement of TAG levels.LDs were stained with fluorescence dye and observed by confocal fluorescence microscopy.TAG levels were determined with an enzyme-based triglyceride assay kit.Colocalization of TMEM68 and DGAT1 was detected by co-expression and confocal fluorescence microscopy and their interaction was determined by co-immunoprecipitation.RT-qPCR and immunoblotting assay were used to detect the expression of DGAT1.Results The synthesis of TAG catalyzed by TMEM68 was independent of DGAT activity.Surplus exogenous fatty acids and monoacylglycerol promoted TAG synthesis mainly through DGAT in human neuroblastoma cells.The LDs formed by TMEM68 were different in morphology from those by DGAT.In addition,TMEM68 and DGAT1 colocalized in the same endoplasmic reticulum(ER)compartment but did not interact physically.TMEM68 overexpression reduced the expression of DGAT1,the major DGAT enzyme involved in TAG synthesis,while TMEM68 knockout had little impact.Conclusion The TMEM68-mediated TAG synthesis pathway has distinct features from the canonical DGAT pathway,however,TMEM68 and DGAT may coregulate intracellular TAG levels.展开更多
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
Nanolipid carriers and traditional emulsion containing chemical sunscreens were prepared using emulsification combined with ultrasonic technology.The nanolipid carriers showed superior performance in sunscreen encapsu...Nanolipid carriers and traditional emulsion containing chemical sunscreens were prepared using emulsification combined with ultrasonic technology.The nanolipid carriers showed superior performance in sunscreen encapsulation,slow release and skin impermeability,and provided an excellent nanolipid slow-release encapsulation system for sunscreens.As observed by transmission electron microscopy,the nanolipid carriers were spherical shape,with smooth surface and uniform distribution,and the particle sizes were mainly concentrated in the range of 230 to 250 nm without agglomeration.The nanolipid carriers significantly improved the sunscreen performance through the synergistic effect of scattering and chemical absorption,and showed better UV stability than traditional sunscreen,indicating their photoprotective function.In vitro release experiments showed that the nano-lipidic carriers exhibited better release control when loaded with octyl methoxycinnamate(OMC)and butylmethoxydibenzoylmethane(BDFM)sunscreens than traditional traditional emulsions,with the cumulative release rate of OMC in the nano-lipidic carriers decreasing by 17.17% to 30.24% within 12 hours,and that of BDFM decreasing by 26.67% to 44.67%.26.67% to 44.16%.The results of the in vitro permeation experiment further confirmed that the nanolipid carriers could effectively encapsulate the sunscreens and prevent them from penetrating the skin barrier,thus reducing the skin irritation.Compared with traditional traditional emulsion,the cumulative penetration of OMC in nanostructured lipid carriers was 2.24μg/cm^(2)in 4 hours,while the cumulative penetration was reduced by 68.05%.The cumulative penetration of BDFM in the nanostructured lipid carrier was 3.24μg/cm^(2),with a 64.04%reduction in cumulative penetration.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
基金funded by Basic Research Program of Shanghai,No.20JC1412200(to JW)the National Key Research and Development Program of China,No.2020YFA0113000(to RCZ)。
文摘Lipid droplets serve as primary storage organelles for neutral lipids in neurons,glial cells,and other cells in the nervous system.Lipid droplet formation begins with the synthesis of neutral lipids in the endoplasmic reticulum.Previously,lipid droplets were recognized for their role in maintaining lipid metabolism and energy homeostasis;however,recent research has shown that lipid droplets are highly adaptive organelles with diverse functions in the nervous system.In addition to their role in regulating cell metabolism,lipid droplets play a protective role in various cellular stress responses.Furthermore,lipid droplets exhibit specific functions in neurons and glial cells.Dysregulation of lipid droplet formation leads to cellular dysfunction,metabolic abnormalities,and nervous system diseases.This review aims to provide an overview of the role of lipid droplets in the nervous system,covering topics such as biogenesis,cellular specificity,and functions.Additionally,it will explore the association between lipid droplets and neurodegenerative disorders.Understanding the involvement of lipid droplets in cell metabolic homeostasis related to the nervous system is crucial to determine the underlying causes and in exploring potential therapeutic approaches for these diseases.
文摘When mammals are exposed to cold,their metabolism undergoes substantial changes.The liver plays a central role in maintaining energy homeostasis by shifting from glucose metabolism to lipid catabolism.A recent study by Davidson et al.^([1]),published in Cell Metabolism,highlights a novel mechanism involving lysosomal lipid remodeling during cold adaptation.Specifically,the study reveals that cold exposure elevates hepatic levels of Bis(Monoacylglycerol)Phosphate(BMP)lipids,which are regulated by Transcription Factor EB(TFEB)and Phospholipase A2 group XV(PLA2G15).
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 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.
文摘BACKGROUND Dyslipidemia was strongly linked to stroke,however the relationship between dyslipidemia and its components and ischemic stroke remained unexplained.AIM To investigate the link between longitudinal changes in lipid profiles and dyslipidemia and ischemic stroke in a hypertensive population.METHODS Between 2013 and 2014,6094 hypertension individuals were included in this,and ischemic stroke cases were documented to the end of 2018.Longitudinal changes of lipid were stratified into four groups:(1)Normal was transformed into normal group;(2)Abnormal was transformed into normal group;(3)Normal was transformed into abnormal group;and(4)Abnormal was transformed into abnormal group.To examine the link between longitudinal changes in dyslipidemia along with its components and the risk of ischemic stroke,we utilized multivariate Cox proportional hazards models with hazard ratio(HR)and 95%CI.RESULTS The average age of the participants was 62.32 years±13.00 years,with 329 women making up 54.0%of the sample.Over the course of a mean follow-up of 4.8 years,143 ischemic strokes happened.When normal was transformed into normal group was used as a reference,after full adjustments,the HR for dyslipidemia and ischemic stroke among abnormal was transformed into normal group,normal was transformed into abnormal group and abnormal was transformed into abnormal Wei CC et al.Dyslipidemia changed and ischemic stroke WJCC https://www.wjgnet.com 2 February 6,2025 Volume 13 Issue 4 group were 1.089(95%CI:0.598-1.982;P=0.779),2.369(95%CI:1.424-3.941;P<0.001)and 1.448(95%CI:1.002-2.298;P=0.047)(P for trend was 0.233),respectively.CONCLUSION In individuals with hypertension,longitudinal shifts from normal to abnormal in dyslipidemia-particularly in total and low-density lipoprotein cholesterol-were significantly associated with the risk of ischemic stroke.
基金the financial support from the National Natural Science Foundation of China(Nos.82060626,22004137,22164022,22174147,22074151,22374153,22174148)Excellent Youth scientific and technological talents of Guizhou Province(No.Qiankehe platform talents[2021]5638)+3 种基金Talents of Guizhou Science and Technology Cooperation Platform(No.[2020]4104)Science and Technology Innovation Team of Higher Education of Guizhou Provincial Education Department(No.Qianjiaoji[2023]073)Future Science and Technology Elite Talent Cultivation Project of Zunyi Medical University(No.ZYSE-2021-01)Zunyi Science and Technology Plan Project(No.Zunshi Keren Platform[2023]2)。
文摘Ferroptosis is a new regulated cell death process executed by lipid peroxidation(LPO)of polyunsaturated fatty acids.Lipid droplets(LDs),as an important organelle for lipid storage and metabolism,are probably a major site of LPO and play critical roles in the regulation of ferroptosis.However,the detailed study on LPO in LDs has not been carried out because of the lack of LD-targeting tools for the in situ monitoring of LPO.Herein,the first LD-targeting LPO fluorescence probe(LD-LPO)has been developed.LD-LPO exhibits a rapid and selective fluorescence enhancement at 518 nm,which is unaffected by highly destructive reactive oxygen species(e.g.,hydroxyl radical)and environmental factor changes(e.g.,polarity and viscosity).LD-LPO is capable of targeting LDs and visualizing LPO within LDs in situ during erastin-or(1S,3R)-RSL3(RSL3)-induced ferroptosis.Moreover,LD-LPO has also been used to image LPO in the ferroptosis-associated non-alcoholic fatty liver disease(NAFLD),and to evaluate the medicine treatment of NAFLD with saroglitazar,demonstrating its utility for monitoring LPO levels in biosystems.The favorable analytical and imaging performance of LD-LPO may allow its application in more ferroptosisassociated physiological and pathological processes.
基金Supported by Joint TCM Science&Technology Projects of National Demonstration Zones for Comprehensive TCM Reform,No.GZYKJS-ZJ-2025-044Ningbo Top Medical and Health Research Program,No.2023020612.
文摘BACKGROUND Metabolic dysfunction-associated steatotic liver disease(MASLD)has emerged as a prominent and pervasive global health challenge.Bicuculline(BIC),which is a key active component of the anti-MASLD prescription"Eight Zhes Decoction",has been preliminarily shown by our research team to have significant potential in treating MASLD.AIM To determine BIC's efficacy in treating MASLD by regulating lipid metabolism and suppressing hepatic inflammation via nuclear factor-kappa B(NF-κB)pathway,identifying it as a therapeutic candidate.METHODS This study explored the potential of BIC in preventing and treating MASLD using zebrafish,cellular(HepG2 and AML12),and mouse models.RESULTS Our results indicate that BIC significantly reduces lipid accumulation and inflammation both in vivo and in vitro.Transcriptomic analysis suggested that the anti-MASLD effects of BIC are linked to the inhibition of the NF-κB pathway,which plays a critical role in mitigating inflammation and lipid deposition.CONCLUSION This study is the first to demonstrate that BIC specifically alleviates lipid accumulation and hepatic steatosis in MASLD models via the NF-κB signaling pathway.Overall,BIC has emerged as a promising candidate for treating MASLD.
基金funded by the National Natural Science Foundation of China(31901624)the Key-Area Research and Development Program of Guangdong Province(2018B020206001)+2 种基金Guangdong Province Zhujiang Talent Program(2019ZT08H476)Shenzhen Science and Technology Program(KQTD20180412181334790)the Innovation Team Project of Universities in Guangdong Province(2020KCXTD023)。
文摘Fucoxanthin,a kind of exclusively algae-derived carotenoids,could reduce lipid content and regulate gut microbiota composition in obese mice,showing potential in preventing hyperlipidemia.This study aimed to illustrate fucoxanthin efficacy in modulating lipid metabolism in serum and liver of high-fat-induced hyperlipidemia mice,as well as investigate the underlying association with gut microbiota changes.Results showed that fucoxanthin significantly reduced body weight gain and body white fat of the mice.In the serum,total triglycerides(TG),total cholesterol(TC)contents were significantly decreased and high-densitylipoprotein cholesterol levels was significantly upregulated.Moreover,fucoxanthin remarkedly prevented lipid accumulation in the liver.Especially,metabolomics results showed that lipids and lipid-like molecules were significantly downregulated compared with the control,indicating the advance of hepatic lipid metabolism.Bile acids profile in the liver was also greatly changed by fucoxanthin.Meanwhile,fucoxanthin remodeled gut microbiota composition and promoted the relative abundance of Desulfovibrio,Blautia and Clostridia genera.Finally,correlation analysis revealed that these gut microbiota changes were closely related with hepatic metabolites/metabolism and serum lipids.Altogether,this study showed great potential of fucoxanthin in improving serum lipids profile,hepatic lipids and bile acids metabolism of hyperlipidemia mice,which was associated with gut microbiota alteration.
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 National Natural Science Foundation of China (Nos. 81903384and 82173596)Suzhou Municipal Science and Technology Bureau (No. SKY2023041 and SKY2023180)+3 种基金the Inner Mongolia Autonomous Region Science and Technology Program (Nos.2022YFSH0054 and 2023GLLH0387)the Clinical Research Center of Neurological Disease of The Second Affiliated Hospital of Soochow University(ND2023B06)the Shaanxi Provincial Natural Science Basic Research Program (2025JC-YBMS-1020)Undergraduate Extracurricular Academic Research Funding of Soochow University (KY2023442B)
文摘Objective Lipid oxidation is involved in the pathogenesis of atherosclerosis and may be contribute to the development of Ischemic stroke(IS).However,the lipid profiles associated with IS have been poorly studied.We conducted a pilot study to identify potential IS-related lipid molecules and pathways using lipidomic profiling.Methods Serum lipidomic profiling was performed using LC-MS in 20 patients with IS and 20 age-and sex-matched healthy controls.Univariate and multivariate analyses were simultaneously performed to identify the differential lipids.Multiple testing was controlled for using a false discovery rate(FDR)approach.Enrichment analysis was performed using MetaboAnalyst software.Results Based on the 294 lipids assayed,principal component analysis(PCA)and orthogonal partial least squares discriminant analysis(OPLS-DA)models were used to distinguish patients with IS from healthy controls.Fifty-six differential lipids were identified with an FDR-adjusted P less than 0.05 and variable influences in projection(VIP)greater than 1.0.These lipids were significantly enriched in glycerophospholipid metabolism(FDR-adjusted P=0.009,impact score=0.216).Conclusions Serum lipid profiles differed significantly between patients with IS and healthy controls.Thus,glycerophospholipid metabolism may be involved in the development of IS.These results provide initial evidence that lipid molecules and their related metabolites may serve as new biomarkers and potential therapeutic targets for IS.
基金financially supported by the National Natural Science Foundation of China(No.22074111)National Key Research and Development Program of China(No.2021YFC2700700)the Opening fund of Hubei Key Laboratory of Bioinorganic Chemistry&Materia Medica(No.BCMM202303)。
文摘As more and more studies have shown that lipid molecules play an important role in the whole biology,in-depth analysis of lipid structure has become particularly important in lipidomics.Mass spectrometry(MS),as the preferred tool for lipid analysis,has greatly promoted the development of this field.However,the existing MS methods still face many difficulties in the in-depth or even comprehensive analysis of lipid structure.In this review,we discuss recent advances in MS methods based on double bond-specific chemistries for the resolving of C=C location and geometry isomers of lipids.This progress has greatly advanced the lipidomics analysis to a deeper structural level and facilitated the development of structural lipid biology.
基金supported by grants from the National Natural Science Foundation of China(22076104)the“Taishan Scholars”Program for Young Expert of Shandong Province(tsqn202103105).
文摘Ferroptosis,a type of programmed cell death,represents a distinct paradigm in cell biology.It is characterized by the iron-dependent accumulation of reactive oxygen species,which induce lipid peroxidation(LPO),and is orchestrated by the interplay between iron,lipid peroxides,and glutathione.In this review,we emphasize the frequently overlooked role of iron in LPO beyond the classical iron-driven Fenton reaction in several crucial processes that regulate cellular iron homeostasis,including iron intake and export as well as ferritinophagy,and the emerging roles of endoplasmic reticulum-resident flavoprotein oxidoreductases,especially P450 oxidoreductases,in modulating LPO.We summarize how various types of fatty acids(FAs),including saturated,monounsaturated,and polyunsaturated FAs,differentially influence ferroptosis when incorporated into phospholipids.Furthermore,we highlight the therapeutic potential of targeting LPO to mitigate ferroptosis and discuss the regulatory mechanisms of endogenous lipophilic radical-trapping antioxidants that confer resistance to ferroptosis,shedding light on therapeutic avenues for ferroptosis-associated diseases.
基金supported by the China Scholarship Council(to YW)the Swedish Research Council,No.2018-02601(to MS)+7 种基金the Alzheimer Foundation,No.AF-980695(to MS)the Stockholm County Council,No.RS2020-0731(to MS)the Foundation of Old Servants(to MS)the Gun and Bertil Stohne Foundation(to MS)the?hlén Foundation,No.233055(to MS)The Swedish Fund for Research without Animal Experiments(to MS)the Swedish Dementia Foundation(to MS)the Brain foundation,No.FO2022-0131(to MS)。
文摘Specialized pro-resolving lipid mediators including maresin 1 mediate resolution but the levels of these are reduced in Alzheimer's disease brain, suggesting that they constitute a novel target for the treatment of Alzheimer's disease to prevent/stop inflammation and combat disease pathology. Therefore, it is important to clarify whether they counteract the expression of genes and proteins induced by amyloid-β. With this objective, we analyzed the relevance of human monocyte–derived microglia for in vitro modeling of neuroinflammation and its resolution in the context of Alzheimer's disease and investigated the pro-resolving bioactivity of maresin 1 on amyloid-β42–induced Alzheimer's disease–like inflammation. Analysis of RNA-sequencing data and secreted proteins in supernatants from the monocyte-derived microglia showed that the monocyte-derived microglia resembled Alzheimer's disease–like neuroinflammation in human brain microglia after incubation with amyloid-β42. Maresin 1 restored homeostasis by down-regulating inflammatory pathway related gene expression induced by amyloid-β42 in monocyte-derived microglia, protection of maresin 1 against the effects of amyloid-β42 is mediated by a re-balancing of inflammatory transcriptional networks in which modulation of gene transcription in the nuclear factor-kappa B pathway plays a major part. We pinpointed molecular targets that are associated with both neuroinflammation in Alzheimer's disease and therapeutic targets by maresin 1. In conclusion, monocyte-derived microglia represent a relevant in vitro microglial model for studies on Alzheimer's disease-like inflammation and drug response for individual patients. Maresin 1 ameliorates amyloid-β42–induced changes in several genes of importance in Alzheimer's disease, highlighting its potential as a therapeutic target for Alzheimer's disease.
基金Supported by Pudong New Area Science and Technology Development Fund for Livelihood Research Special Project,No.PKJ2023-Y38.
文摘BACKGROUND Colorectal cancer(CRC)is a prevalent malignant neoplasm characterized by subtle early manifestations.AIM To investigate the correlation among serum lipid profiles,the triglyceride-glucose(TyG)index,and the atherosclerotic index(AI)in patients with CRC.Furthermore,it explored the clinical diagnostic utility of combining serum lipids with cancer antigens in the context of CRC.METHODS A retrospective analysis encompassed 277 patients with CRC and 1034 healthy individuals.RESULTS Following propensity score matching,patients with CRC exhibited significantly reduced levels of serum triglyceride(TG),total cholesterol(TC),high-density lipoprotein cholesterol,and low-density lipoprotein cholesterol(LDL-C),as well as a diminished TyG index.Conversely,they displayed elevated AI levels compared to their healthy counterparts.Patients in advanced stages exhibited lower serum levels of TG,TC,and LDL-C compared to those in early stages.Patients with positive lymph node metastasis demonstrated reduced levels of TG,LDL-C,and the TyG index.Receiver operating characteristic analysis revealed that the combination of the TyG index,carcinoembryonic antigen,and carbohydrate antigen 19-9 yielded the highest positive prediction rate for CRC at 75.3%.CONCLUSION Preoperative serum lipid profiles exhibit a robust association with patients with CRC.The concurrent assessment of multiple serum lipids and cancer antigens effectively enhances the diagnostic accuracy for CRC.
文摘Objective To characterize transmembrane protein 68(TMEM68)in an alternative triacylglycerol(TAG)biosynthesis pathway,and determine the interplay between TMEM68 and the canonical TAG synthesis enzyme acyl-CoA:diacylglycerol acyltransferase(DGAT).Methods Effects of exogenous fatty acid and monoacylglycerol on TAG synthesis and lipid droplet(LD)formation in TMEM68 overexpression and knockout cells treated with DGAT inhibitor or not were investigated by comparing LD morphology,Oil Red O staining,and measurement of TAG levels.LDs were stained with fluorescence dye and observed by confocal fluorescence microscopy.TAG levels were determined with an enzyme-based triglyceride assay kit.Colocalization of TMEM68 and DGAT1 was detected by co-expression and confocal fluorescence microscopy and their interaction was determined by co-immunoprecipitation.RT-qPCR and immunoblotting assay were used to detect the expression of DGAT1.Results The synthesis of TAG catalyzed by TMEM68 was independent of DGAT activity.Surplus exogenous fatty acids and monoacylglycerol promoted TAG synthesis mainly through DGAT in human neuroblastoma cells.The LDs formed by TMEM68 were different in morphology from those by DGAT.In addition,TMEM68 and DGAT1 colocalized in the same endoplasmic reticulum(ER)compartment but did not interact physically.TMEM68 overexpression reduced the expression of DGAT1,the major DGAT enzyme involved in TAG synthesis,while TMEM68 knockout had little impact.Conclusion The TMEM68-mediated TAG synthesis pathway has distinct features from the canonical DGAT pathway,however,TMEM68 and DGAT may coregulate intracellular TAG levels.
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.
文摘Nanolipid carriers and traditional emulsion containing chemical sunscreens were prepared using emulsification combined with ultrasonic technology.The nanolipid carriers showed superior performance in sunscreen encapsulation,slow release and skin impermeability,and provided an excellent nanolipid slow-release encapsulation system for sunscreens.As observed by transmission electron microscopy,the nanolipid carriers were spherical shape,with smooth surface and uniform distribution,and the particle sizes were mainly concentrated in the range of 230 to 250 nm without agglomeration.The nanolipid carriers significantly improved the sunscreen performance through the synergistic effect of scattering and chemical absorption,and showed better UV stability than traditional sunscreen,indicating their photoprotective function.In vitro release experiments showed that the nano-lipidic carriers exhibited better release control when loaded with octyl methoxycinnamate(OMC)and butylmethoxydibenzoylmethane(BDFM)sunscreens than traditional traditional emulsions,with the cumulative release rate of OMC in the nano-lipidic carriers decreasing by 17.17% to 30.24% within 12 hours,and that of BDFM decreasing by 26.67% to 44.67%.26.67% to 44.16%.The results of the in vitro permeation experiment further confirmed that the nanolipid carriers could effectively encapsulate the sunscreens and prevent them from penetrating the skin barrier,thus reducing the skin irritation.Compared with traditional traditional emulsion,the cumulative penetration of OMC in nanostructured lipid carriers was 2.24μg/cm^(2)in 4 hours,while the cumulative penetration was reduced by 68.05%.The cumulative penetration of BDFM in the nanostructured lipid carrier was 3.24μg/cm^(2),with a 64.04%reduction in cumulative penetration.
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.
