Low-density lipoprotein receptor-related protein 2(LRP2)is a multifunctional endocytic receptor expressed in epithelial cells.In mammals,it acts as an endocytic receptor that mediates the cellular uptake of cholestero...Low-density lipoprotein receptor-related protein 2(LRP2)is a multifunctional endocytic receptor expressed in epithelial cells.In mammals,it acts as an endocytic receptor that mediates the cellular uptake of cholesterol-containing apolipoproteins to maintain lipid homeostasis.However,little is known about the role of LRP2 in lipid homeostasis in insects.In the present study,we investigated the function of LRP2 in the migratory locust Locusta migratoria(LmLRP2).The mRNA of LmLRP2 is widely distributed in various tissues,including integument,wing pads,foregut,midgut,hindgut,Malpighian tubules and fat body,and the amounts of LmLRP2 transcripts decreased gradually in the early stages and then increased in the late stages before ecdysis during the nymphal developmental stage.Fluorescence immunohistochemistry revealed that the LmLRP2 protein is mainly located in cellular membranes of the midgut and hindgut.Using RNAi to silence LmLRP2 caused molting defects in nymphs(more than 60%),and the neutral lipid was found to accumulate in the midgut and surface of the integument,but not in the fat body,of dsLmLRP2-treated nymphs.The results of a lipidomics analysis showed that the main components of lipids(diglyceride and triglyceride)were significantly increased in the midgut,but decreased in the fat body and hemolymph.Furthermore,the content of total triglyceride was significantly increased in the midgut,but markedly decreased in the fat body and hemolymph in dsLmLRP2-injected nymphs.Our results indicate that LmLRP2 is located in the cellular membranes of midgut cells,and is required for lipid export from the midgut to the hemolymphand fat body in locusts.展开更多
Apolipoprotein E is the major lipid transporter in the brain and an important player in neuron-astrocyte metabolic coupling.It ensures the survival of neurons under stressful conditions and hyperactivity by nourishing...Apolipoprotein E is the major lipid transporter in the brain and an important player in neuron-astrocyte metabolic coupling.It ensures the survival of neurons under stressful conditions and hyperactivity by nourishing and detoxifying them.Apolipoprotein E polymorphism,combined with environmental stresses and/or age-related alterations,influences the risk of developing late-onset Alzheimer’s disease.In this review,we discuss our current knowledge of how apolipoprotein E homeostasis,i.e.its synthesis,secretion,degradation,and lipidation,is affected in Alzheimer’s disease.展开更多
The impact of apolipoprotein E(ApoE)isoforms on sporadic Alzheimer's disease has long been studied;however,the influences of apolipoprotein E gene(APOE)on healthy and pathological human brains are not fully unders...The impact of apolipoprotein E(ApoE)isoforms on sporadic Alzheimer's disease has long been studied;however,the influences of apolipoprotein E gene(APOE)on healthy and pathological human brains are not fully understood.ApoE exists as three common isoforms(ApoE2,ApoE3,and ApoE4),which differ in two amino acid residues.Traditionally,ApoE binds cholesterol and phospholipids and ApoE isoforms display diffe rent affinities for their receptors,lipids transport and distribution in the brain and periphery.The role of ApoE in the human depends on ApoE isoforms,brain regions,aging,and neural injury.APOE E4 is the strongest genetic risk factor for sporadic Alzheimer's disease,considering its role in influencing amyloid-beta metabolism.The exact mechanisms by which APOE gene variants may increase or decrease Alzheimer's disease risk are not fully understood,but APOE was also known to affect directly and indirectly tau-mediated neurodegeneration,lipids metabolism,neurovascular unit,and microglial function.Consistent with the biological function of ApoE,ApoE4 isoform significantly alte red signaling pathways associated with cholesterol homeostasis,transport,and myelination.Also,the rare protective APOE variants confirm that ApoE plays an important role in Alzheimer's disease pathogenesis.The objectives of the present mini-review were to describe classical and new roles of various ApoE isoforms in Alzheimer's disease pathophysiology beyond the deposition of amyloid-beta and to establish a functional link between APOE,brain function,and memory,from a molecular to a clinical level.APOE genotype also exerted a heterogeneous effect on clinical Alzheimer's disease phenotype and its outcomes.Not only in learning and memory but also in neuro psychiatric symptoms that occur in a premorbid condition.Cla rifying the relationships between Alzheimer's disease-related pathology with neuropsychiatric symptoms,particularly suicidal ideation in Alzheimer's disease patients,may be useful for elucidating also the underlying pathophysiological process and its prognosis.Also,the effects of anti-amyloid-beta drugs,recently approved for the treatment of Alzheimer's disease,could be influenced by the APOE genotype.展开更多
Liver cirrhosis is the common endpoint of many hepatic diseases and represents a relevant risk for liver failure and hepatocellular carcinoma.The progress of liver fibrosis and cirrhosis is accompanied by deterioratin...Liver cirrhosis is the common endpoint of many hepatic diseases and represents a relevant risk for liver failure and hepatocellular carcinoma.The progress of liver fibrosis and cirrhosis is accompanied by deteriorating liver function.This review summarizes the regulatory and functional changes in phase Ⅰ and phaseⅡmetabolic enzymes as well as transport proteins and provides an overview regarding lipid and glucose metabolism in cirrhotic patients.Interestingly,phase Ⅰ enzymes are generally down regulated transcriptionally,while phaseⅡenzymes are mostly preserved transcriptionally but are reduced in their function.Transport proteins are regulated in a specific way that resembles the molecular changes observed in obstructive cholestasis.Lipid and glucose metabolism are characterized by insulin resistance and catabolism,leading to the disturbance of energy expenditure and wasting.Possible non-invasive tests,especially breath tests,for components of liver metabolism are discussed.The heterogeneity and complexity of changes in hepatic metabolism complicate the assessment of liver function in individual patients.Additionally,studies in humans are rare,and species differences preclude the transferability of data from rodents to humans.In clinical practice,some established global scores or criteria form the basis for the functional evaluation of patients with liver cirrhosis,but difficult treatment decisions such as selection for transplantation or resection require further research regarding the application of existing non-invasive tests and the development of more specific tests.展开更多
Lipid dysmetabolism is one of the main features of diabetes mellitus and manifests by dyslipidemia as well as the ectopic accumulation of lipids in various tissues and organs,including the kidney.Research suggests tha...Lipid dysmetabolism is one of the main features of diabetes mellitus and manifests by dyslipidemia as well as the ectopic accumulation of lipids in various tissues and organs,including the kidney.Research suggests that impaired cholesterol metabolism,increased lipid uptake or synthesis,increased fatty acid oxidation,lipid droplet accumulation and an imbalance in biologically active sphingolipids(such as ceramide,ceramide-1-phosphate and sphingosine-1-phosphate)contribute to the development of diabetic kidney disease(DKD).Currently,the literature suggests that both quality and quantity of lipids are associated with DKD and contribute to increased reactive oxygen species production,oxidative stress,inflammation,or cell death.Therefore,control of renal lipid dysmetabolism is a very important therapeutic goal,which needs to be archived.This article will review some of the recent advances leading to a better understanding of the mechanisms of dyslipidemia and the role of particular lipids and sphingolipids in DKD.展开更多
Tumours are known to be a heterogeneous group of cells,which is why they are difficult to eradicate.One possible cause for this is the existence of slow-cycling cancer stem cells(CSCs)endowed with stem cell-like prope...Tumours are known to be a heterogeneous group of cells,which is why they are difficult to eradicate.One possible cause for this is the existence of slow-cycling cancer stem cells(CSCs)endowed with stem cell-like properties of self-renewal,which are responsible for resistance to chemotherapy and radiotherapy.In recent years,the role of lipid metabolism has garnered increasing attention in cancer.Specifically,the key roles of enzymes such as stearoyl-CoA desaturase-1 and 3-hydroxy-3-methyl-glutaryl-coenzyme A reductase in CSCs,have gained particular interest.However,despite accumulating evidence on the role of proteins in controlling lipid metabolism,very little is known about the specific role played by lipid products in CSCs.This review highlights recent findings on the role of lipid metabolism in CSCs,focusing on the specific mechanism by which bioactive lipids regulate the fate of CSCs and their involvement in signal transduction pathways.展开更多
Objective: Single nucleotide polymorphisms (SNP) of ATP-binding cassette transporter A1 (ABCA1) gene are related to plasma lipid and susceptibility to coronary artery disease (CAD). Our first goal was to screen all 50...Objective: Single nucleotide polymorphisms (SNP) of ATP-binding cassette transporter A1 (ABCA1) gene are related to plasma lipid and susceptibility to coronary artery disease (CAD). Our first goal was to screen all 50 coding regions of ABCA1 to find new SNPs. Our second goal was to investigate the frequency distribution of R1587K and M883I polymorphisms of ABCA1 gene, which are the variant occurred most frequently, in Chinese people and to evaluate their association with the CAD phenotype and plasma lipids. Methods: Single-strand conformation polymorphism (SSCP) and DNA sequence were used for confirming new SNP of ABCA1, and restriction fragment length polymorphism (RFLP) were applied for confirming genotypes of R1587K and M883I in 112 CAD cases and 108 healthy people. Results: We discovered a new ABCA1 SNP in Chinese population, which converse 233 amino acids from Methionine to Valine (M233V). This new ABCA1 SNP located in exon7, and might potentially modulate the biological function of lipid metabolism. For R1587K and M883I SNPs, the K allele and I allele frequency was 28.9%and 31.1%, respectively. The K allele at R1587K conferred lower mean values of HDL-C in a dose-dependent manner in both CAD patients and healthy people. However, 883I allele was not associated with plasma lipid level. Neither 1587KK nor 883II associated with increased risk of CAD. Conclusion: Our study finds a potential functional ABCA1 SNPs and revealed K allele of R1587K associated decreased HDL-C level in Chinese population.展开更多
基金supported by the National Key R&D Program of China (2022YFE0196200)the National Natural Science Foundation of China–Deutsche Forschungsgemeinschaft of Germany (31761133021)+3 种基金the National Natural Science Foundation of China (31970469 and 31701794)the earmarked fund for Modern Agro-industry Technology Research System, China (2023CYJSTX01-20)the Scientific and Technological Innovation Programs of Higher Education Institutions in Shanxi, China (2017104)the Fund for Shanxi “1331 Project”, China
文摘Low-density lipoprotein receptor-related protein 2(LRP2)is a multifunctional endocytic receptor expressed in epithelial cells.In mammals,it acts as an endocytic receptor that mediates the cellular uptake of cholesterol-containing apolipoproteins to maintain lipid homeostasis.However,little is known about the role of LRP2 in lipid homeostasis in insects.In the present study,we investigated the function of LRP2 in the migratory locust Locusta migratoria(LmLRP2).The mRNA of LmLRP2 is widely distributed in various tissues,including integument,wing pads,foregut,midgut,hindgut,Malpighian tubules and fat body,and the amounts of LmLRP2 transcripts decreased gradually in the early stages and then increased in the late stages before ecdysis during the nymphal developmental stage.Fluorescence immunohistochemistry revealed that the LmLRP2 protein is mainly located in cellular membranes of the midgut and hindgut.Using RNAi to silence LmLRP2 caused molting defects in nymphs(more than 60%),and the neutral lipid was found to accumulate in the midgut and surface of the integument,but not in the fat body,of dsLmLRP2-treated nymphs.The results of a lipidomics analysis showed that the main components of lipids(diglyceride and triglyceride)were significantly increased in the midgut,but decreased in the fat body and hemolymph.Furthermore,the content of total triglyceride was significantly increased in the midgut,but markedly decreased in the fat body and hemolymph in dsLmLRP2-injected nymphs.Our results indicate that LmLRP2 is located in the cellular membranes of midgut cells,and is required for lipid export from the midgut to the hemolymphand fat body in locusts.
基金supported by the financial support of the Louis-Jeantet Foundation(to ACG).
文摘Apolipoprotein E is the major lipid transporter in the brain and an important player in neuron-astrocyte metabolic coupling.It ensures the survival of neurons under stressful conditions and hyperactivity by nourishing and detoxifying them.Apolipoprotein E polymorphism,combined with environmental stresses and/or age-related alterations,influences the risk of developing late-onset Alzheimer’s disease.In this review,we discuss our current knowledge of how apolipoprotein E homeostasis,i.e.its synthesis,secretion,degradation,and lipidation,is affected in Alzheimer’s disease.
文摘The impact of apolipoprotein E(ApoE)isoforms on sporadic Alzheimer's disease has long been studied;however,the influences of apolipoprotein E gene(APOE)on healthy and pathological human brains are not fully understood.ApoE exists as three common isoforms(ApoE2,ApoE3,and ApoE4),which differ in two amino acid residues.Traditionally,ApoE binds cholesterol and phospholipids and ApoE isoforms display diffe rent affinities for their receptors,lipids transport and distribution in the brain and periphery.The role of ApoE in the human depends on ApoE isoforms,brain regions,aging,and neural injury.APOE E4 is the strongest genetic risk factor for sporadic Alzheimer's disease,considering its role in influencing amyloid-beta metabolism.The exact mechanisms by which APOE gene variants may increase or decrease Alzheimer's disease risk are not fully understood,but APOE was also known to affect directly and indirectly tau-mediated neurodegeneration,lipids metabolism,neurovascular unit,and microglial function.Consistent with the biological function of ApoE,ApoE4 isoform significantly alte red signaling pathways associated with cholesterol homeostasis,transport,and myelination.Also,the rare protective APOE variants confirm that ApoE plays an important role in Alzheimer's disease pathogenesis.The objectives of the present mini-review were to describe classical and new roles of various ApoE isoforms in Alzheimer's disease pathophysiology beyond the deposition of amyloid-beta and to establish a functional link between APOE,brain function,and memory,from a molecular to a clinical level.APOE genotype also exerted a heterogeneous effect on clinical Alzheimer's disease phenotype and its outcomes.Not only in learning and memory but also in neuro psychiatric symptoms that occur in a premorbid condition.Cla rifying the relationships between Alzheimer's disease-related pathology with neuropsychiatric symptoms,particularly suicidal ideation in Alzheimer's disease patients,may be useful for elucidating also the underlying pathophysiological process and its prognosis.Also,the effects of anti-amyloid-beta drugs,recently approved for the treatment of Alzheimer's disease,could be influenced by the APOE genotype.
文摘Liver cirrhosis is the common endpoint of many hepatic diseases and represents a relevant risk for liver failure and hepatocellular carcinoma.The progress of liver fibrosis and cirrhosis is accompanied by deteriorating liver function.This review summarizes the regulatory and functional changes in phase Ⅰ and phaseⅡmetabolic enzymes as well as transport proteins and provides an overview regarding lipid and glucose metabolism in cirrhotic patients.Interestingly,phase Ⅰ enzymes are generally down regulated transcriptionally,while phaseⅡenzymes are mostly preserved transcriptionally but are reduced in their function.Transport proteins are regulated in a specific way that resembles the molecular changes observed in obstructive cholestasis.Lipid and glucose metabolism are characterized by insulin resistance and catabolism,leading to the disturbance of energy expenditure and wasting.Possible non-invasive tests,especially breath tests,for components of liver metabolism are discussed.The heterogeneity and complexity of changes in hepatic metabolism complicate the assessment of liver function in individual patients.Additionally,studies in humans are rare,and species differences preclude the transferability of data from rodents to humans.In clinical practice,some established global scores or criteria form the basis for the functional evaluation of patients with liver cirrhosis,but difficult treatment decisions such as selection for transplantation or resection require further research regarding the application of existing non-invasive tests and the development of more specific tests.
基金the National Institute of Health(Research in Dr.Alessia Fornoni’s laboratory),No.R01DK117599,No.R01DK104753,No.R01CA227493,No.U54DK083912,No.UM1DK100846,and No.U01DK116101the Miami Clinical Translational Science Institute,No.UL1TR000460and the Chernowitz Medical Research Foundation(Mitrofanova A and Burke G),No.GR016291.
文摘Lipid dysmetabolism is one of the main features of diabetes mellitus and manifests by dyslipidemia as well as the ectopic accumulation of lipids in various tissues and organs,including the kidney.Research suggests that impaired cholesterol metabolism,increased lipid uptake or synthesis,increased fatty acid oxidation,lipid droplet accumulation and an imbalance in biologically active sphingolipids(such as ceramide,ceramide-1-phosphate and sphingosine-1-phosphate)contribute to the development of diabetic kidney disease(DKD).Currently,the literature suggests that both quality and quantity of lipids are associated with DKD and contribute to increased reactive oxygen species production,oxidative stress,inflammation,or cell death.Therefore,control of renal lipid dysmetabolism is a very important therapeutic goal,which needs to be archived.This article will review some of the recent advances leading to a better understanding of the mechanisms of dyslipidemia and the role of particular lipids and sphingolipids in DKD.
文摘Tumours are known to be a heterogeneous group of cells,which is why they are difficult to eradicate.One possible cause for this is the existence of slow-cycling cancer stem cells(CSCs)endowed with stem cell-like properties of self-renewal,which are responsible for resistance to chemotherapy and radiotherapy.In recent years,the role of lipid metabolism has garnered increasing attention in cancer.Specifically,the key roles of enzymes such as stearoyl-CoA desaturase-1 and 3-hydroxy-3-methyl-glutaryl-coenzyme A reductase in CSCs,have gained particular interest.However,despite accumulating evidence on the role of proteins in controlling lipid metabolism,very little is known about the specific role played by lipid products in CSCs.This review highlights recent findings on the role of lipid metabolism in CSCs,focusing on the specific mechanism by which bioactive lipids regulate the fate of CSCs and their involvement in signal transduction pathways.
基金Supported by the Natural Scientific Foundation of China (30471929)
文摘Objective: Single nucleotide polymorphisms (SNP) of ATP-binding cassette transporter A1 (ABCA1) gene are related to plasma lipid and susceptibility to coronary artery disease (CAD). Our first goal was to screen all 50 coding regions of ABCA1 to find new SNPs. Our second goal was to investigate the frequency distribution of R1587K and M883I polymorphisms of ABCA1 gene, which are the variant occurred most frequently, in Chinese people and to evaluate their association with the CAD phenotype and plasma lipids. Methods: Single-strand conformation polymorphism (SSCP) and DNA sequence were used for confirming new SNP of ABCA1, and restriction fragment length polymorphism (RFLP) were applied for confirming genotypes of R1587K and M883I in 112 CAD cases and 108 healthy people. Results: We discovered a new ABCA1 SNP in Chinese population, which converse 233 amino acids from Methionine to Valine (M233V). This new ABCA1 SNP located in exon7, and might potentially modulate the biological function of lipid metabolism. For R1587K and M883I SNPs, the K allele and I allele frequency was 28.9%and 31.1%, respectively. The K allele at R1587K conferred lower mean values of HDL-C in a dose-dependent manner in both CAD patients and healthy people. However, 883I allele was not associated with plasma lipid level. Neither 1587KK nor 883II associated with increased risk of CAD. Conclusion: Our study finds a potential functional ABCA1 SNPs and revealed K allele of R1587K associated decreased HDL-C level in Chinese population.
