More than four decades ago it was established that an elevated low-density lipoprotein-cholesterol level was a risk for developing coronary artery disease. For the last two decades, statins have been the cornerstone o...More than four decades ago it was established that an elevated low-density lipoprotein-cholesterol level was a risk for developing coronary artery disease. For the last two decades, statins have been the cornerstone of reducing low-density lipoprotein-cholesterol, but despite significant clinical efficacy in the majority of patients, a large number of patients suffer from side effects and cannot tolerate the required statin dose to reach their recommended low-density lipoprotein-cholesterol goals. Preliminary clinical studies indicate that monoclonal antibodies to PCSK9 appear to be highly efficacious in lowering low-density lipoprotein-cholesterol with a favourable adverse event profile. However, further longer-term clinical studies are required to determine their safety. From the early-proposed concept for high-density lipoprotein-mediated cholesterol efflux for the treatment of coronary artery disease, the concentration of the cholesterol content in high-density lipoprotein particles has been considered a surrogate measurement for the efficacy of the reverse cholesterol transport process. However, unlike the beneficial effects of the statins and monoclonal antibodies to PCSK9 in reducing low-density lipoprotein-cholesterol, no significant advances have been made to increase the levels of high-density lipoprotein-cholesterol. Here it is shown that by a non-pharmacological plasma delipidation means, the atherogenic low-density lipoproteins can be converted to anti-atherogenic particles and that the high-density lipoproteins are converted to particles with extreme high affinity to cause rapid regression of atherosclerosis.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
Plant oils are increasingly sought after as sustainable sources of bioenergy for biodiesel production and high-value biochemicals.Although oilseed crops currently serve as the primary source of plant oils,meeting the ...Plant oils are increasingly sought after as sustainable sources of bioenergy for biodiesel production and high-value biochemicals.Although oilseed crops currently serve as the primary source of plant oils,meeting the rising global demand on limited arable land,without compromising food security,remains a major challenge.Therefore,metabolic engineering of high-biomass bioenergy feedstocks has been widely explored to enhance the conversion of carbon stored in vegetative tissues into energy-dense triacylglycerol(TAG).Significant progress has been made in boosting TAG accumulation in the vegetative tissues of various plant species through bioengineering strategies.These efforts span from single-gene modifications to the coordinated expression of key lipogenic factors such as WRI1,DGAT1/2,and OLE1.The resulting fatty acid and TAG profiles,however,often vary depending on the targeted plant species and promoter(s)used.This review summarizes the roles of essential lipogenic factors in plant oil biosynthesis and highlights recent advances in metabolic engineering across diverse crop species through combinatorial expression of these factors.We also discuss future strategies for achieving high-level oil production without incurring growth penalties.By offering new perspectives on metabolic engineering,this work aims to support the development of plants as efficient biofuel feedstocks,contributing to the global effort to address energy challenges.展开更多
Antimicrobial peptides(AMPs)are potentially powerful alternatives to conven-tional antibiotics in combating multidrug resistance,given their broad spectrum of activity.They mainly interact with cell membranes through ...Antimicrobial peptides(AMPs)are potentially powerful alternatives to conven-tional antibiotics in combating multidrug resistance,given their broad spectrum of activity.They mainly interact with cell membranes through surface electrostatic potentials and the formation of secondary structures,resulting in permeability and destruction of target microorganism membranes.Our earlier work showed that two leading AMPs,MSI-78(4–20)and pardaxin(1–22),had potent antimicrobial activ-ity against a range of bacteria.It is known that the attachment of moderate-length lipid carbon chains to cationic peptides can further improve the functionality of these peptides through enhanced interactions with the membrane lipid bilayer,inducing membrane curvature,destabilization,and potential leakage.Thus,in this work,we aimed to investigate the antimicrobial activity,oligomerization propensity,and lipid-membrane binding interactions of a range of N-terminal lipidated analogs of MSI-78(4–20)and pardaxin(1–22).Molecular modeling results suggest that aggregation of the N-lipidated AMPs may impart greater structural stability to the peptides in solu-tion and a greater depth of lipid bilayer insertion for the N-lipidated AMPs over the parental peptide.Our experimental and computationalfindings provide insights into how N-terminal lipidation of AMPs may alter their conformations,with subsequent effects on their functional properties in regard to their self-aggregation behavior,membrane interactions,and antimicrobial activity.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
Metabolic dysfunction-associated steatotic liver disease(MASLD)has become the most prevalent chronic liver disease worldwide,affecting approximately 32%-38%of the adult population and posing a growing public health bu...Metabolic dysfunction-associated steatotic liver disease(MASLD)has become the most prevalent chronic liver disease worldwide,affecting approximately 32%-38%of the adult population and posing a growing public health burden.MASLD represents a continuous disease spectrum ranging from simple steatosis to metabolic dysfunction-associated steatohepatitis(MASH),progressive hepatic fibrosis,cirrhosis,and ultimately hepatocellular carcinoma(HCC).The pathological core of MASLD lies in disruption of hepatic lipid metabolic homeostasis,characterized by an imbalance among de novo lipogenesis,fatty acidβ-oxidation,and very-low-density lipoprotein(VLDL)-mediated lipid export.This metabolic disequilibrium subsequently drives inflammatory injury and fibrotic progression.Among the multiple regulatory pathways involved,thyroid hormone(TH)signaling has emerged as a central regulator of hepatic metabolic homeostasis.The liver is a major peripheral target organ of TH action,where TH predominantly exerts its metabolic effects through thyroid hormone receptorβ(TRβ).Large-scale epidemiological studies and metaanalyses have demonstrated that hypothyroidism is significantly associated with increased MASLD prevalence,more severe histological injury,and advanced hepatic fibrosis,suggesting that dysregulation of TH signaling may participate throughout the entire MASLD disease spectrum.At the molecular level,TH regulates hepatic lipid metabolism by coordinating suppression of lipogenesis,enhancement of mitochondrial fatty acid oxidation,and promotion of VLDL assembly and secretion through integrated genomic actions of the T3-TRβaxis and non-genomic signaling pathways.Across different stages of MASLD,TH signaling exerts stagedependent protective effects.In the steatosis stage,TH improves metabolic flexibility by modulating insulin sensitivity,glucose metabolism,and lipid droplet clearance,thereby alleviating early lipotoxic stress.During progression to MASH,TH attenuates inflammatory amplification by improving mitochondrial homeostasis,suppressing activation of the NOD-like receptor family pyrin domain containing 3(NLRP3)inflammasome,and modulating the gut-liver axis microenvironment.In advanced stages,TH signaling influences hepatic stellate cell activation and extracellular matrix deposition,partly through interaction with the transforming growth factor-β(TGF-β)/SMAD pathway,while alterations in intrahepatic TH availability,mediated by dynamic changes in iodothyronine deiodinase 1(DIO1),contribute to fibrosis progression and hepatocellular dedifferentiation.In hepatocellular carcinoma,coordinated downregulation of TRβand DIO1 establishes a tumor-associated hypothyroid state that promotes metabolic reprogramming and tumor progression.The clinical relevance of TH signaling in MASLD has been underscored by the recent approval of Resmetirom,a liver-targeted TRβ-selective agonist,for the treatment of non-cirrhotic MASH with moderate-to-severe fibrosis(F2-F3).This approval represents a landmark transition from mechanistic understanding to metabolismcentered precision therapy in MASLD.Clinical trials have demonstrated that Resmetirom not only improves key histological endpoints,including MASH resolution and fibrosis regression,but also favorably modulates atherogenic lipid profiles,highlighting the therapeutic potential of selectively targeting hepatic TH pathways.This review systematically summarizes the multidimensional regulatory roles of TH across the MASLD disease spectrum and discusses emerging diagnostic and therapeutic implications of THbased interventions,aiming to inform future mechanistic research and optimize clinical management strategies.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
Traumatic spinal cord injury often leads to the disintegration of nerve cells and axons,resulting in a substantial accumulation of myelin debris that can persist for years.The abnormal buildup of myelin debris at site...Traumatic spinal cord injury often leads to the disintegration of nerve cells and axons,resulting in a substantial accumulation of myelin debris that can persist for years.The abnormal buildup of myelin debris at sites of injury greatly impedes nerve regeneration,making the clearance of debris within these microenvironments crucial for effective post-spinal cord injury repair.In this review,we comprehensively outline the mechanisms that promote the clearance of myelin debris and myelin metabolism and summarize their roles in spinal cord injury.First,we describe the composition and characteristics of myelin debris and explain its effects on the injury site.Next,we introduce the phagocytic cells involved in myelin debris clearance,including professional phagocytes(macrophages and microglia)and non-professional phagocytes(astrocytes and microvascular endothelial cells),as well as other cells that are also proposed to participate in phagocytosis.Finally,we focus on the pathways and associated targets that enhance myelin debris clearance by phagocytes and promote lipid metabolism following spinal cord injury.Our analysis indicates that myelin debris phagocytosis is not limited to monocyte-derived macrophages,but also involves microglia,astrocytes,and microvascular endothelial cells.By modulating the expression of genes related to phagocytosis and lipid metabolism,it is possible to modulate lipid metabolism disorders and influence inflammatory phenotypes,ultimately affecting the recovery of motor function following spinal cord injury.Additionally,therapies such as targeted mitochondrial transplantation in phagocytic cells,exosome therapy,and repeated trans-spinal magnetic stimulation can effectively enhance the removal of myelin debris,presenting promising potential for future applications.展开更多
Lysophosphatidic acid(LPA)is a pleiotropic lipid agonist essential for functions of the central nervous system(CNS).It is abundant in the developing and adult brain while its concentration in biological fluids,includi...Lysophosphatidic acid(LPA)is a pleiotropic lipid agonist essential for functions of the central nervous system(CNS).It is abundant in the developing and adult brain while its concentration in biological fluids,including cerebrospinal fluid,varies significantly(Figure 1Α;Yung et al.,2014).LPA actually corresponds to a variety of lipid species that include different stereoisomers with either saturated or unsaturated fatty acids bearing likely differentiated biological activities(Figure 1Α;Yung et al.,2014;Hernández-Araiza et al.,2018).展开更多
Tumor metabolic reprogramming is a core hallmark of cancer,characterized by pathways such as aerobic glycolysis,aberrant lipid metabolism,and glutaminolysis that support rapid proliferation and immunosuppressive micro...Tumor metabolic reprogramming is a core hallmark of cancer,characterized by pathways such as aerobic glycolysis,aberrant lipid metabolism,and glutaminolysis that support rapid proliferation and immunosuppressive microenvironments.Circular RNAs(circRNAs)are highly stable,evolutionarily conserved non-coding RNAs that have emerged as critical modulators of these metabolic shifts.This review aims to systematically elucidate the roles and mechanisms of circRNAs in reprogramming tumor metabolism,and to discuss their clinical potential as biomarkers and therapeutic targets.Through mechanisms including miRNA sponging,protein interactions,regulation of mitochondrial dynamics,and modulation of metabolic enzymes,circRNAs influence key metabolic pathways by targeting glycolytic enzymes,lipid synthesis regulators,and glutaminolysis-related molecules to either facilitate or inhibit their expression.This review systematically summarizes the unique contributions of circRNAs to tumor metabolic reprogramming,highlighting key mechanisms such as regulation of peptide-encoding protein translation,mitochondrial localization function,gene promoter-targeted transcriptional regulation,and cross-pathway metabolic mediation,which underscore their distinct biological advantages and regulatory roles in tumor metabolism.The stability and tissue specificity of circRNAs make them promising diagnostic biomarkers,while their role in drug resistance mediated by metabolic reprogramming highlights their potential as therapeutic targets.Strategies such as circRNA inhibitors,mimics,and nanoparticle-based delivery systems are being explored to modulate tumor metabolism.Despite challenges including complex regulatory networks and limited manipulation tools,advances in high-throughput technologies and clinical trials hold promise for translating circRNA research into novel cancer therapies.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
AIM:To clarify the clinical correlations and causal relationships between lipid metabolism and the progression of thyroid-associated ophthalmopathy(TAO).METHODS:This case-control study retrieved clinical data from 201...AIM:To clarify the clinical correlations and causal relationships between lipid metabolism and the progression of thyroid-associated ophthalmopathy(TAO).METHODS:This case-control study retrieved clinical data from 2018 to 2023.A total of 2591 patients were enrolled,including 197 patients with TAO(case group)and 2394 patients with hyperthyroidism without TAO(control group).Serum lipid parameters,including triglycerides,total cholesterol,high-density lipoprotein(HDL),low-density lipoprotein(LDL),and the HDL/total cholesterol ratio,as well as thyroid function markers,were compared between the two groups.Correlation analyses were performed to evaluate the associations between serum lipid levels and key ocular manifestations of TAO,including exophthalmos degree,clinical activity score,and disease severity.Furthermore,Mendelian randomization(MR)analysis was conducted using genome-wide association study(GWAS)datasets,with hyperthyroidism as the exposure variable and serum lipid parameters as the outcome variables,to infer the causal relationship between hyperthyroidism,lipid metabolism,and TAO progression.RESULTS:The TAO group consisted of 101 males and 96 females,while the hyperthyroidism group included 706 males and 1688 females.Compared with the control group,patients with TAO had significantly higher levels of triglycerides(1.83±1.21 vs 1.40±1.08 mmol/L,P<0.01),total cholesterol,LDL,and HDL.Correlation analysis showed that triglyceride levels were positively correlated with exophthalmos degree,whereas HDL levels were inversely correlated with exophthalmos degree.No significant associations were found between serum lipid levels and clinical activity score(P>0.1).MR analysis confirmed that hyperthyroidism exerted a causal effect in reducing serum triglycerides[inverse-variance weighting odds ratio(OR)=0.035,95%confidence interval(CI):0.01-0.12]and total cholesterol(OR=0.085,95%CI:0.02-0.34),with no evidence of horizontal pleiotropy(MR-PRESSO P>0.05).CONCLUSION:Elevated serum triglyceride levels are an independent risk factor for TAO severity,especially exophthalmos,and triglyceride metabolism is inversely regulated by thyroid function.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
Reproductive diapause is an insect survival strategy in which reproduction temporarily halts in response to adverse environmental changes.This process is characterized by arrested ovarian development and lipid accumul...Reproductive diapause is an insect survival strategy in which reproduction temporarily halts in response to adverse environmental changes.This process is characterized by arrested ovarian development and lipid accumulation in females.A reduction in juvenile hormone(JH)biosynthesis is known to initiate reproductive diapause,but its regulatory mechanism remains unclear.Seven up(Svp),a transcription factor from the nuclear receptor family,plays a crucial role in various developmental processes in insects.In this study,using the cabbage beetle Colaphellus bowringi as a model,we observed higher expression of Svp in the heads of female adults under reproductive photoperiodic conditions(short-day[SD])compared to diapause conditions(long-day[LD]).RNA interference-mediated knockdown of Svp in SD females induced typical diapause phenotypes,including ovarian arrest and lipid accumulation.The application of methoprene(ME),a JH receptor agonist,reversed these diapause phenotypes and restored reproduction,indicating that Svp’s regulation of reproductive diapause is dependent on JH signaling.Additionally,Svp knockdown led to the downregulation of JH pathway genes and a reduction in JH titers.Further evidence suggested that Svp regulates the expression of JHAMT1,a critical gene in JH biosynthesis,which determines diapause entry in C.bowringi.These findings suggest that diapause-inducing photoperiods suppress Svp expression,blocking JH production and triggering diapause.This work reveals a critical transcription factor that regulates reproductive diapause initiation through modulating JH production,providing a potential target for controlling pests capable of entering reproductive diapause.展开更多
Carnauba wax-structured soybean oil oleogels were developed as alternative frying media for proso millet rice cake processing.Optimal practical properties were identified in the 8%wax concentration through evaluations...Carnauba wax-structured soybean oil oleogels were developed as alternative frying media for proso millet rice cake processing.Optimal practical properties were identified in the 8%wax concentration through evaluations conducted via polarized light microscopy,oil holding capacity,freeze-thaw stability,and rheological analysis.Oleogel-fried cakes were found to exhibit 6.69%–19.98%lower oil absorption compared to soybean oil-fried samples during 0–18 h frying.The corresponding low-field NMR results demonstrated that the percentage of the relaxation peak area attributed to oil content in oleogel-fried proso millet rice cakes was also reduced.The lipid oxidation rates were significantly reduced in oleogels(P<0.05),with total polar compounds(9.89%–22.81%)and acid values(4.21%–24.37%)decreased while thermal stability was maintained.Saturated fatty acid levels in oleogel were reduced by 3.18%–7.26%after frying for 12–18 h.Texture properties were slightly affected whereas color attributes were significantly improved.Enhanced texture,flavor,hardness,and mouthfeel in oleogel-fried products were confirmed through sensory evaluation.Volatile components,particularly ketones and esters were significantly increased in rice cakes fried with oleogel.These results might offer novel insights for advancement of future low-oil frying technologies and expand the application of oleogels.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
Oleaginous yeasts hold significant potential as biodiesel feedstocks as they accumulate high content of lipids with similar fatty acid profiles to those of plant oils.However,the commercialization of yeast lipids is l...Oleaginous yeasts hold significant potential as biodiesel feedstocks as they accumulate high content of lipids with similar fatty acid profiles to those of plant oils.However,the commercialization of yeast lipids is limited by the high cost of nutrients for yeast cultivation.This study aimed to explore the use of agro-industrial carbon wastes as low-cost nutrients and cultivation strategies for promising oleaginous yeasts.Four oleaginous yeasts were screened for their ability to grow on molasses,crude glycerol,and whey lactose.Among the yeast strains and agro-industrial wastes tested,Candida tropicalis X37 and Rhodotorula mucilaginosa G43 grew best on molasses and produced higher lipids than other strains.Both strains grew better when adding ammonium sulfate as a low-cost nitrogen source,but C.tropicalis X37 produced higher lipids when using only molasses.Through the fed-batch cultivation,C.tropicalis X37 could thrive in high molasses concentration and gave higher biomass and lipids than R.mucilaginosa G43.Scaling up in a bioreactor using an aeration rate of 1.0 air volume per liquid volume per minute further increased the production of biomass and lipids by C.tropicalis X37 up to 15.75±0.42 g/L and 6.55±0.35 g/L,respectively.The analysis of prospective fuel properties confirmed that the yeast lipids are suitable as biodiesel feedstocks.These strategies would contribute greatly to supporting green energy supply,sustainable management of wastes,and environmental protection.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
文摘More than four decades ago it was established that an elevated low-density lipoprotein-cholesterol level was a risk for developing coronary artery disease. For the last two decades, statins have been the cornerstone of reducing low-density lipoprotein-cholesterol, but despite significant clinical efficacy in the majority of patients, a large number of patients suffer from side effects and cannot tolerate the required statin dose to reach their recommended low-density lipoprotein-cholesterol goals. Preliminary clinical studies indicate that monoclonal antibodies to PCSK9 appear to be highly efficacious in lowering low-density lipoprotein-cholesterol with a favourable adverse event profile. However, further longer-term clinical studies are required to determine their safety. From the early-proposed concept for high-density lipoprotein-mediated cholesterol efflux for the treatment of coronary artery disease, the concentration of the cholesterol content in high-density lipoprotein particles has been considered a surrogate measurement for the efficacy of the reverse cholesterol transport process. However, unlike the beneficial effects of the statins and monoclonal antibodies to PCSK9 in reducing low-density lipoprotein-cholesterol, no significant advances have been made to increase the levels of high-density lipoprotein-cholesterol. Here it is shown that by a non-pharmacological plasma delipidation means, the atherogenic low-density lipoproteins can be converted to anti-atherogenic particles and that the high-density lipoproteins are converted to particles with extreme high affinity to cause rapid regression of atherosclerosis.
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the Natural Science Foundation of China(32300231)to Jiang Wangthe Natural Science Foundation of Hainan Province(324MS023)to Jiang Wang.
文摘Plant oils are increasingly sought after as sustainable sources of bioenergy for biodiesel production and high-value biochemicals.Although oilseed crops currently serve as the primary source of plant oils,meeting the rising global demand on limited arable land,without compromising food security,remains a major challenge.Therefore,metabolic engineering of high-biomass bioenergy feedstocks has been widely explored to enhance the conversion of carbon stored in vegetative tissues into energy-dense triacylglycerol(TAG).Significant progress has been made in boosting TAG accumulation in the vegetative tissues of various plant species through bioengineering strategies.These efforts span from single-gene modifications to the coordinated expression of key lipogenic factors such as WRI1,DGAT1/2,and OLE1.The resulting fatty acid and TAG profiles,however,often vary depending on the targeted plant species and promoter(s)used.This review summarizes the roles of essential lipogenic factors in plant oil biosynthesis and highlights recent advances in metabolic engineering across diverse crop species through combinatorial expression of these factors.We also discuss future strategies for achieving high-level oil production without incurring growth penalties.By offering new perspectives on metabolic engineering,this work aims to support the development of plants as efficient biofuel feedstocks,contributing to the global effort to address energy challenges.
基金The National Health and Medical Research Council,Grant/Award Numbers:APP2018256,APP1142472,APP1158841,APP1185426Australian Research Council,Grant/Award Numbers:FT210100271,DP210102781,DP160101312,LE200100163+5 种基金Cancer Council Victoria funding,Grant/Award Number:APP1163284Australia-China Science and Research Fund-Joint Research Centre on Personal Health Technologies,Grant/Award Number:ACSRF65777Australian Dental Research Foundation GrantPawsey Supercomputing CentreNational Computational InfrastructureAustralian National Fabrication Facility,Grant/Award Number:VictorianNode。
文摘Antimicrobial peptides(AMPs)are potentially powerful alternatives to conven-tional antibiotics in combating multidrug resistance,given their broad spectrum of activity.They mainly interact with cell membranes through surface electrostatic potentials and the formation of secondary structures,resulting in permeability and destruction of target microorganism membranes.Our earlier work showed that two leading AMPs,MSI-78(4–20)and pardaxin(1–22),had potent antimicrobial activ-ity against a range of bacteria.It is known that the attachment of moderate-length lipid carbon chains to cationic peptides can further improve the functionality of these peptides through enhanced interactions with the membrane lipid bilayer,inducing membrane curvature,destabilization,and potential leakage.Thus,in this work,we aimed to investigate the antimicrobial activity,oligomerization propensity,and lipid-membrane binding interactions of a range of N-terminal lipidated analogs of MSI-78(4–20)and pardaxin(1–22).Molecular modeling results suggest that aggregation of the N-lipidated AMPs may impart greater structural stability to the peptides in solu-tion and a greater depth of lipid bilayer insertion for the N-lipidated AMPs over the parental peptide.Our experimental and computationalfindings provide insights into how N-terminal lipidation of AMPs may alter their conformations,with subsequent effects on their functional properties in regard to their self-aggregation behavior,membrane interactions,and antimicrobial activity.
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.
文摘Metabolic dysfunction-associated steatotic liver disease(MASLD)has become the most prevalent chronic liver disease worldwide,affecting approximately 32%-38%of the adult population and posing a growing public health burden.MASLD represents a continuous disease spectrum ranging from simple steatosis to metabolic dysfunction-associated steatohepatitis(MASH),progressive hepatic fibrosis,cirrhosis,and ultimately hepatocellular carcinoma(HCC).The pathological core of MASLD lies in disruption of hepatic lipid metabolic homeostasis,characterized by an imbalance among de novo lipogenesis,fatty acidβ-oxidation,and very-low-density lipoprotein(VLDL)-mediated lipid export.This metabolic disequilibrium subsequently drives inflammatory injury and fibrotic progression.Among the multiple regulatory pathways involved,thyroid hormone(TH)signaling has emerged as a central regulator of hepatic metabolic homeostasis.The liver is a major peripheral target organ of TH action,where TH predominantly exerts its metabolic effects through thyroid hormone receptorβ(TRβ).Large-scale epidemiological studies and metaanalyses have demonstrated that hypothyroidism is significantly associated with increased MASLD prevalence,more severe histological injury,and advanced hepatic fibrosis,suggesting that dysregulation of TH signaling may participate throughout the entire MASLD disease spectrum.At the molecular level,TH regulates hepatic lipid metabolism by coordinating suppression of lipogenesis,enhancement of mitochondrial fatty acid oxidation,and promotion of VLDL assembly and secretion through integrated genomic actions of the T3-TRβaxis and non-genomic signaling pathways.Across different stages of MASLD,TH signaling exerts stagedependent protective effects.In the steatosis stage,TH improves metabolic flexibility by modulating insulin sensitivity,glucose metabolism,and lipid droplet clearance,thereby alleviating early lipotoxic stress.During progression to MASH,TH attenuates inflammatory amplification by improving mitochondrial homeostasis,suppressing activation of the NOD-like receptor family pyrin domain containing 3(NLRP3)inflammasome,and modulating the gut-liver axis microenvironment.In advanced stages,TH signaling influences hepatic stellate cell activation and extracellular matrix deposition,partly through interaction with the transforming growth factor-β(TGF-β)/SMAD pathway,while alterations in intrahepatic TH availability,mediated by dynamic changes in iodothyronine deiodinase 1(DIO1),contribute to fibrosis progression and hepatocellular dedifferentiation.In hepatocellular carcinoma,coordinated downregulation of TRβand DIO1 establishes a tumor-associated hypothyroid state that promotes metabolic reprogramming and tumor progression.The clinical relevance of TH signaling in MASLD has been underscored by the recent approval of Resmetirom,a liver-targeted TRβ-selective agonist,for the treatment of non-cirrhotic MASH with moderate-to-severe fibrosis(F2-F3).This approval represents a landmark transition from mechanistic understanding to metabolismcentered precision therapy in MASLD.Clinical trials have demonstrated that Resmetirom not only improves key histological endpoints,including MASH resolution and fibrosis regression,but also favorably modulates atherogenic lipid profiles,highlighting the therapeutic potential of selectively targeting hepatic TH pathways.This review systematically summarizes the multidimensional regulatory roles of TH across the MASLD disease spectrum and discusses emerging diagnostic and therapeutic implications of THbased interventions,aiming to inform future mechanistic research and optimize clinical management strategies.
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.82271411(to RG),51803072(to WL)the International Cooperative Project of Talent Cultivation“Xinghai Project”at the China-Japan Union Hospital of Jilin University,No.XHLH202404(to WL)+1 种基金the Science and Technology Development Plan of Jilin Province,No.YDZJ202201ZYTS038(to WL)Jilin Provincial Finance Program,No.2022SCZ10(to WL)。
文摘Traumatic spinal cord injury often leads to the disintegration of nerve cells and axons,resulting in a substantial accumulation of myelin debris that can persist for years.The abnormal buildup of myelin debris at sites of injury greatly impedes nerve regeneration,making the clearance of debris within these microenvironments crucial for effective post-spinal cord injury repair.In this review,we comprehensively outline the mechanisms that promote the clearance of myelin debris and myelin metabolism and summarize their roles in spinal cord injury.First,we describe the composition and characteristics of myelin debris and explain its effects on the injury site.Next,we introduce the phagocytic cells involved in myelin debris clearance,including professional phagocytes(macrophages and microglia)and non-professional phagocytes(astrocytes and microvascular endothelial cells),as well as other cells that are also proposed to participate in phagocytosis.Finally,we focus on the pathways and associated targets that enhance myelin debris clearance by phagocytes and promote lipid metabolism following spinal cord injury.Our analysis indicates that myelin debris phagocytosis is not limited to monocyte-derived macrophages,but also involves microglia,astrocytes,and microvascular endothelial cells.By modulating the expression of genes related to phagocytosis and lipid metabolism,it is possible to modulate lipid metabolism disorders and influence inflammatory phenotypes,ultimately affecting the recovery of motor function following spinal cord injury.Additionally,therapies such as targeted mitochondrial transplantation in phagocytic cells,exosome therapy,and repeated trans-spinal magnetic stimulation can effectively enhance the removal of myelin debris,presenting promising potential for future applications.
基金supported by the Hellenic Foundation for Research and Innovation,HFRI,“2nd Call for HFRI Research Projects to support Faculty Members&Researchers”Project 02667 to GL.
文摘Lysophosphatidic acid(LPA)is a pleiotropic lipid agonist essential for functions of the central nervous system(CNS).It is abundant in the developing and adult brain while its concentration in biological fluids,including cerebrospinal fluid,varies significantly(Figure 1Α;Yung et al.,2014).LPA actually corresponds to a variety of lipid species that include different stereoisomers with either saturated or unsaturated fatty acids bearing likely differentiated biological activities(Figure 1Α;Yung et al.,2014;Hernández-Araiza et al.,2018).
基金funded by National Natural Science Foundation of China(82360801).
文摘Tumor metabolic reprogramming is a core hallmark of cancer,characterized by pathways such as aerobic glycolysis,aberrant lipid metabolism,and glutaminolysis that support rapid proliferation and immunosuppressive microenvironments.Circular RNAs(circRNAs)are highly stable,evolutionarily conserved non-coding RNAs that have emerged as critical modulators of these metabolic shifts.This review aims to systematically elucidate the roles and mechanisms of circRNAs in reprogramming tumor metabolism,and to discuss their clinical potential as biomarkers and therapeutic targets.Through mechanisms including miRNA sponging,protein interactions,regulation of mitochondrial dynamics,and modulation of metabolic enzymes,circRNAs influence key metabolic pathways by targeting glycolytic enzymes,lipid synthesis regulators,and glutaminolysis-related molecules to either facilitate or inhibit their expression.This review systematically summarizes the unique contributions of circRNAs to tumor metabolic reprogramming,highlighting key mechanisms such as regulation of peptide-encoding protein translation,mitochondrial localization function,gene promoter-targeted transcriptional regulation,and cross-pathway metabolic mediation,which underscore their distinct biological advantages and regulatory roles in tumor metabolism.The stability and tissue specificity of circRNAs make them promising diagnostic biomarkers,while their role in drug resistance mediated by metabolic reprogramming highlights their potential as therapeutic targets.Strategies such as circRNA inhibitors,mimics,and nanoparticle-based delivery systems are being explored to modulate tumor metabolism.Despite challenges including complex regulatory networks and limited manipulation tools,advances in high-throughput technologies and clinical trials hold promise for translating circRNA research into novel cancer therapies.
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.
基金Supported by the National Natural Science Foundation of China(No.82371104)the Natural Science Foundation of Hunan Province(No.2023JJ30851).
文摘AIM:To clarify the clinical correlations and causal relationships between lipid metabolism and the progression of thyroid-associated ophthalmopathy(TAO).METHODS:This case-control study retrieved clinical data from 2018 to 2023.A total of 2591 patients were enrolled,including 197 patients with TAO(case group)and 2394 patients with hyperthyroidism without TAO(control group).Serum lipid parameters,including triglycerides,total cholesterol,high-density lipoprotein(HDL),low-density lipoprotein(LDL),and the HDL/total cholesterol ratio,as well as thyroid function markers,were compared between the two groups.Correlation analyses were performed to evaluate the associations between serum lipid levels and key ocular manifestations of TAO,including exophthalmos degree,clinical activity score,and disease severity.Furthermore,Mendelian randomization(MR)analysis was conducted using genome-wide association study(GWAS)datasets,with hyperthyroidism as the exposure variable and serum lipid parameters as the outcome variables,to infer the causal relationship between hyperthyroidism,lipid metabolism,and TAO progression.RESULTS:The TAO group consisted of 101 males and 96 females,while the hyperthyroidism group included 706 males and 1688 females.Compared with the control group,patients with TAO had significantly higher levels of triglycerides(1.83±1.21 vs 1.40±1.08 mmol/L,P<0.01),total cholesterol,LDL,and HDL.Correlation analysis showed that triglyceride levels were positively correlated with exophthalmos degree,whereas HDL levels were inversely correlated with exophthalmos degree.No significant associations were found between serum lipid levels and clinical activity score(P>0.1).MR analysis confirmed that hyperthyroidism exerted a causal effect in reducing serum triglycerides[inverse-variance weighting odds ratio(OR)=0.035,95%confidence interval(CI):0.01-0.12]and total cholesterol(OR=0.085,95%CI:0.02-0.34),with no evidence of horizontal pleiotropy(MR-PRESSO P>0.05).CONCLUSION:Elevated serum triglyceride levels are an independent risk factor for TAO severity,especially exophthalmos,and triglyceride metabolism is inversely regulated by thyroid function.
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funded by the National Natural Science Foundation of China,China(grant no.32472543).
文摘Reproductive diapause is an insect survival strategy in which reproduction temporarily halts in response to adverse environmental changes.This process is characterized by arrested ovarian development and lipid accumulation in females.A reduction in juvenile hormone(JH)biosynthesis is known to initiate reproductive diapause,but its regulatory mechanism remains unclear.Seven up(Svp),a transcription factor from the nuclear receptor family,plays a crucial role in various developmental processes in insects.In this study,using the cabbage beetle Colaphellus bowringi as a model,we observed higher expression of Svp in the heads of female adults under reproductive photoperiodic conditions(short-day[SD])compared to diapause conditions(long-day[LD]).RNA interference-mediated knockdown of Svp in SD females induced typical diapause phenotypes,including ovarian arrest and lipid accumulation.The application of methoprene(ME),a JH receptor agonist,reversed these diapause phenotypes and restored reproduction,indicating that Svp’s regulation of reproductive diapause is dependent on JH signaling.Additionally,Svp knockdown led to the downregulation of JH pathway genes and a reduction in JH titers.Further evidence suggested that Svp regulates the expression of JHAMT1,a critical gene in JH biosynthesis,which determines diapause entry in C.bowringi.These findings suggest that diapause-inducing photoperiods suppress Svp expression,blocking JH production and triggering diapause.This work reveals a critical transcription factor that regulates reproductive diapause initiation through modulating JH production,providing a potential target for controlling pests capable of entering reproductive diapause.
基金the National Natural Science Foundation of China Youth Fund(NO:322019447)Yulin city 2nd Science and Technology Light“Scientist+Engineer”Team Project(2024-KJZG-K+G-017)Shaanxi Science and Technology Innovation Team Project(2024RS-CXTD-70)for the financial support.
文摘Carnauba wax-structured soybean oil oleogels were developed as alternative frying media for proso millet rice cake processing.Optimal practical properties were identified in the 8%wax concentration through evaluations conducted via polarized light microscopy,oil holding capacity,freeze-thaw stability,and rheological analysis.Oleogel-fried cakes were found to exhibit 6.69%–19.98%lower oil absorption compared to soybean oil-fried samples during 0–18 h frying.The corresponding low-field NMR results demonstrated that the percentage of the relaxation peak area attributed to oil content in oleogel-fried proso millet rice cakes was also reduced.The lipid oxidation rates were significantly reduced in oleogels(P<0.05),with total polar compounds(9.89%–22.81%)and acid values(4.21%–24.37%)decreased while thermal stability was maintained.Saturated fatty acid levels in oleogel were reduced by 3.18%–7.26%after frying for 12–18 h.Texture properties were slightly affected whereas color attributes were significantly improved.Enhanced texture,flavor,hardness,and mouthfeel in oleogel-fried products were confirmed through sensory evaluation.Volatile components,particularly ketones and esters were significantly increased in rice cakes fried with oleogel.These results might offer novel insights for advancement of future low-oil frying technologies and expand the application of oleogels.
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 by Faculty of Agro-Industry and National Science,Research and Innovation Fund(NSRF)and Prince of Songkla University(Ref.No.AGR6701270b)National Research Council of Thailand(NRCT):Contract number N42A680491.
文摘Oleaginous yeasts hold significant potential as biodiesel feedstocks as they accumulate high content of lipids with similar fatty acid profiles to those of plant oils.However,the commercialization of yeast lipids is limited by the high cost of nutrients for yeast cultivation.This study aimed to explore the use of agro-industrial carbon wastes as low-cost nutrients and cultivation strategies for promising oleaginous yeasts.Four oleaginous yeasts were screened for their ability to grow on molasses,crude glycerol,and whey lactose.Among the yeast strains and agro-industrial wastes tested,Candida tropicalis X37 and Rhodotorula mucilaginosa G43 grew best on molasses and produced higher lipids than other strains.Both strains grew better when adding ammonium sulfate as a low-cost nitrogen source,but C.tropicalis X37 produced higher lipids when using only molasses.Through the fed-batch cultivation,C.tropicalis X37 could thrive in high molasses concentration and gave higher biomass and lipids than R.mucilaginosa G43.Scaling up in a bioreactor using an aeration rate of 1.0 air volume per liquid volume per minute further increased the production of biomass and lipids by C.tropicalis X37 up to 15.75±0.42 g/L and 6.55±0.35 g/L,respectively.The analysis of prospective fuel properties confirmed that the yeast lipids are suitable as biodiesel feedstocks.These strategies would contribute greatly to supporting green energy supply,sustainable management of wastes,and environmental protection.
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.
