Sleep benefits the restoration of energy metabolism and thereby suppo rts neuronal plasticity and cognitive behaviors.Sirt6 is a NAD+-dependent protein deacetylase that has been recognized as an essential regulator of...Sleep benefits the restoration of energy metabolism and thereby suppo rts neuronal plasticity and cognitive behaviors.Sirt6 is a NAD+-dependent protein deacetylase that has been recognized as an essential regulator of energy metabolism because it modulates various transcriptional regulators and metabolic enzymes.The aim of this study was to investigate the influence of Sirt6 on cerebral function after chronic sleep deprivation(CSD).We assigned C57BL/6J mice to control or two CSD groups and subjected them to AAV2/9-CMV-EGFP or AAV2/9-CMV-Sirt6-EGFP infection in the prelimbic cortex(PrL).We then assessed cerebral functional connectivity(FC) using resting-state functional MRI,neuron/astrocyte metabolism using a metabolic kinetics analysis;dendritic spine densities using sparse-labeling;and miniature excitato ry postsynaptic currents(mEPSCs) and action potential(AP) firing rates using whole-cell patchclamp recordings.In addition,we evaluated cognition via a comprehensive set of behavioral tests.Compared with controls,Sirt6 was significantly decreased(P<0.05) in the PrL after CSD,accompanied by cognitive deficits and decreased FC between the PrL and accumbens nucleus,piriform cortex,motor co rtex,somatosensory co rtex,olfactory tubercle,insular cortex,and cerebellum.Sirt6 ove rexpression reve rsed CSD-induced cognitive impairment and reduced FC.Our analysis of metabolic kinetics using [1-13C] glucose and [2-13C] acetate showed that CSD reduced neuronal Glu4and GABA2synthesis,which could be fully restored via forced Sirt6 expression.Furthermore,Sirt6 ove rexpression reversed CSD-induced decreases in AP firing rates as well as the frequency and amplitude of mEPSCs in PrL pyramidal neurons.These data indicate that Sirt6 can improve cognitive impairment after CSD by regulating the PrL-associated FC network,neuronal glucose metabolism,and glutamatergic neurotransmission.Thus,Sirt6 activation may have potential as a novel strategy for treating sleep disorder-related diseases.展开更多
To investigate the effects of impaired glucose metabolism (IGM) on cardiovascular autonomic nervous systems in essential hypertensive (EH) patients by comparing heart rate variability (HRV) and blood pressure va...To investigate the effects of impaired glucose metabolism (IGM) on cardiovascular autonomic nervous systems in essential hypertensive (EH) patients by comparing heart rate variability (HRV) and blood pressure variability (BPV) in EH patients with or without type 2 diabetes mellitus (T2DM). Simultaneous 24-h recordings of ambulatory ECG and blood pressure monitoring were performed in 36 male old patients with simple EH and 33 male old patients with EH combined with T2DM. HRV analysis included time domain parameters such as SDNN, SDANN, SDNNi, rMSSD and pNN50, and total spectral power (TP) of HRV, which mainly consists of VLF, LF and HF component along with LF/HF ratio, was also obtained. The value of ambulatory blood pressure was represented as the mean blood pressure (mean systolic/mSBP, diastolic/mDBP and pulse pressure/mPP) during different periods (24 h/24 h, day time/d and night time/n). Standard deviation (SD) as well as coefficient of variance (CV) of blood pressure during each above-mentioned period were obtained to reflect the long-term BPV. Our result showed that SDNN, SDNNi, SDANN, rMSSD, PNN50, TP and HF of HRV in cases of EH with T2DM were all significantly lower than those in simple EH subjects (P〈0.05). No significant differences in VLF or LF was found between the two groups (P〉0.05), while LF/HF ratio was significantly higher in EH with T2DM patients than in simple EH subjects (P〈0.01). Moreover, dmSBP, 24 h-mPP and dmPP were all significantly higher in EH with T2DM patients than in simple EH subjects (P〈0.05), while nmSBP, 24 h-mSBP, 24 h-mDBP, dmDBP, nmDBP or nmPP showed no significant difference between this two groups of patients (P〉0.05). And dSBPSD, dSBPCV and 24 h-SBPSD were all significantly higher in EH with T2DM patients than in simple EH subjects (P〈0.05), while the other BPV indexes showed no significant difference between this two groups (P〉0.05). It is concluded that the cardiovascular autonomic nervous systems in EH patients was further impaired by T2DM, displaying lowering of HRV and enlargement of BPV, which in turn induced abnormal structural and functional changes of cardiovascular systems. Therefore, improving cardiovascular autonomic nervous systems might reduce the occurrence of cardiovascular complications in the EH patients with IGM.展开更多
The intestinal microbiota regulates mammalian lipid absorption,metabolism,and storage.We report that the microbiota reprograms intestinal lipid metabolism in mice by repressing the expression of long noncoding RNA(lnc...The intestinal microbiota regulates mammalian lipid absorption,metabolism,and storage.We report that the microbiota reprograms intestinal lipid metabolism in mice by repressing the expression of long noncoding RNA(lncRNA)Snhg9(small nucleolar RNA host gene 9)in small intestinal epithelial cells.Snhg9suppressed the activity of peroxisome proliferator-activated receptorγ(PPARγ)-a central regulator of lipid metabolism-by dissociating the PPARγinhibitor sirtuin 1 from cell cycle and apoptosis protein 2(CCAR2).Forced expression ofSnhg9in the intestinal epithelium of conventional mice impaired lipid absorption,reduced body fat,and protected against diet-induced obesity.The microbiota repressedSnhg9expression through an immune relay encompassing myeloid cells and group 3 innate lymphoid cells.Our findings thus identify an unanticipated role for a lncRNA in microbial control of host metabolism.展开更多
Background:Nonalcoholic fatty liver disease(NAFLD)is associated with impaired renal function,and both diseases often occur alongside other metabolic disorders.However,the prevalence and risk factors for impaired renal...Background:Nonalcoholic fatty liver disease(NAFLD)is associated with impaired renal function,and both diseases often occur alongside other metabolic disorders.However,the prevalence and risk factors for impaired renal function in patients with NAFLD remain unclear.The objective of this study was to identify the prevalence and risk factors for renal impairment in NAFLD patients.Methods:All adults aged 18-70 years with ultrasound-diagnosed NAFLD and transient elastography examination from eight Asian centers were enrolled in this prospective study.Liver fibrosis and cirrhosis were assessed by FibroScan-aspartate aminotransferase(FAST),Agile 3+and Agile 4 scores.Impaired renal function and chronic kidney disease(CKD)were defined by an estimated glomerular filtration rate(eGFR)with value of<90 mL/min/1.73 m^(2) and<60 mL/min/1.73 m^(2),respectively,as estimated by the CKD-Epidemiology Collaboration(CKD-EPI)equation.Results:Among 529 included NAFLD patients,the prevalence rates of impaired renal function and CKD were 37.4%and 4.9%,respectively.In multivariate analysis,a moderate-high risk of advanced liver fibrosis and cirrhosis according to Agile 3+and Agile 4 scores were independent risk factors for CKD(P<0.05).Furthermore,increased fasting plasma glucose(FPG)and blood pressure were significantly associated with impaired renal function after controlling for the other components of metabolic syndrome(P<0.05).Compared with patients with normoglycemia,those with prediabetes[FPG≥5.6 mmol/L or hemoglobin A1c(HbA1c)≥5.7%]were more likely to have impaired renal function(P<0.05).Conclusions:Agile 3+and Agile 4 are reliable for identifying NAFLD patients with high risk of CKD.Early glycemic control in the prediabetic stage might have a potential renoprotective role in these patients.展开更多
Alcohol, a widely abused drug, has deleterious effects on the immature nervous system. This study investigates the effect of chronic in vitro ethanol exposure on the metabolism of immature rat cerebellar granular cell...Alcohol, a widely abused drug, has deleterious effects on the immature nervous system. This study investigates the effect of chronic in vitro ethanol exposure on the metabolism of immature rat cerebellar granular cells(CGCs) and on their response to oxygen-glucose deprivation(OGD). Primary CGC cultures were exposed to ethanol(100 mM in culture medium) or to control ethanol-free medium starting day one in vitro(DIV1). At DIV8, the expression of ATP synthase gene ATP5 g3 was quantified using real-time PCR, then cultures were exposed to 3 hours of OGD or normoxic conditions. Subsequently, cellular metabolism was assessed by a resazurin assay and by ATP level measurement. ATP5 g3 expression was reduced by 12-fold(P = 0.03) and resazurin metabolism and ATP level were decreased to 74.4 ± 4.6% and 55.5 ± 6.9%, respectively after chronic ethanol treatment compared to control values(P < 0.01). Additionally, after OGD exposure of ethanol-treated cultures, resazurin metabolism and ATP level were decreased to 12.7 ± 1.0% and 9.0 ± 2.0% from control values(P < 0.01). These results suggest that chronic ethanol exposure reduces the cellular ATP level, possibly through a gene expression down-regulation mechanism, and increases the vulnerability to oxygen-glucose deprivation. Thus, interventions which improve metabolic function and sustain ATP-levels could attenuate ethanol-induced neuronal dysfunction and should be addressed in future studies.展开更多
Anorexia and fasting are host adaptations to acute infection, inducing a metabolic switch towards ketogenesis and the production of ketone bodies, including β-hydroxybutyrate (BHB) 1-6. However, whether ketogenesis m...Anorexia and fasting are host adaptations to acute infection, inducing a metabolic switch towards ketogenesis and the production of ketone bodies, including β-hydroxybutyrate (BHB) 1-6. However, whether ketogenesis metabolically influences the immune response in pulmonary infections remains unclear. Here we report impaired production of BHB in humans with SARS-CoV-2-induced but not influenza-induced acute respiratory distress syndrome (ARDS). CD4^(+) T cell function is impaired in COVID-19 and BHB promotes both survival and production of Interferon-γ from CD4^(+) T cells. Using metabolic tracing analysis, we uncovered that BHB provides an alternative carbon source to fuel oxidative phosphorylation (OXPHOS) and the production of bioenergetic amino acids and glutathione, which is important for maintaining the redox balance. T cells from patients with SARS-CoV-2-induced ARDS were exhausted and skewed towards glycolysis, but can be metabolically reprogrammed by BHB to perform OXPHOS, thereby increasing their functionality.展开更多
AIM:To investigate whether impaired fasting glucose(IFG)confers cardiovascular risk.METHODS:A non-diabetic population-based sample representative of middle-aged and elderly Turks was studied at 8.5 years’follow-up fo...AIM:To investigate whether impaired fasting glucose(IFG)confers cardiovascular risk.METHODS:A non-diabetic population-based sample representative of middle-aged and elderly Turks was studied at 8.5 years’follow-up for incident diabetes and coronary heart disease(CHD).Metabolic syndrome(MetS)was defined by ATP-Ⅲcriteria modifiedfor male abdominal obesity,and IFG and type 2 diabetes were identified by criteria of the American Diabetes Association.Stratification by presence of MetS was used.Outcomes were predicted providing estimates for hazard ratio(HR)obtained by use of Cox proportional hazards regression analysis in models that controlled for potential confounders.RESULTS:In 3181 adults(aged 52±11.5 years at baseline),analysis stratified by MetS,gender and IFG status distinguished normoglycemic subjects by a"hypertriglyceridemic waist"phenotype consisting of significantly higher waist circumference,fasting triglyceride and lower high-density lipoprotein-cholesterol,regardless of gender and MetS.Additionally,lipoprotein(Lp)(a)tended to be lower in(especially female)participants with MetS.Multivariable linear regression in a subset of the sample demonstrated decreased Lp(a)levels to be associated with increased fasting glucose and insulin concentrations,again particularly in women.In Cox regression analysis,compared with normoglycemia,baseline IFG adjusted for major confounders significantly predicted incident diabetes at a 3-fold HR in men and only women with MetS.Cox models for developing CHD in 339 individuals,adjusted for conventional risk factors,revealed that IFG status protected against CHD risk[HR=0.37(95%CI:0.14-0.998)]in subjects free of MetS,a protection that attenuated partly in male and fully in female participants with MetS.CONCLUSION:IFG status in non-diabetic people without MetS displays reduced future CHD risk,yet is modulated by MetS,likely due to autoimmune activation linked to serum Lp(a).展开更多
Objective :To investigate glucose metabolism in women with multiple ovarian follicles (MOF) and explore the relationship between glucose metabolism, insulin resistance and body weight. Methods:We evaluated 46 wome...Objective :To investigate glucose metabolism in women with multiple ovarian follicles (MOF) and explore the relationship between glucose metabolism, insulin resistance and body weight. Methods:We evaluated 46 women with MFO and 30 normal women as controls. All the subjects were given 75g of glucose orally in order to perform the oral glucose tolerance test (OGTT) and insulin releasing test (IRT), and they were also evaluated for insulin resistance using the insulin resistance index with homeostatic model assessment (HOMA). Results:The occurrence of impaired glucose tolerance in women with MOF was 10.87%, which was significantly higher than that in the control group (3.33% ,P 〈 0.05). The rate of insulin resistance was 30.43% in the study group as compared to 10.00% in the control group. The results showed that there was significant difference between the two groups(P 〈 0.05). The levels of FSH,LH,PRL,E2,T and P between the two groups had no significant difference (P 〉 0.05). BMI in women with impaired glucose tolerance was correlated positively to insulin resistance (r = 0.567, P 〈 0.05). Conclusion:Abnormal glucose metabolism was observed in women with unitary multiple ovarian follicles, and this could be attributed to obesity and insulin resistance. Women with MOF and associated obesity should be subjected to OGTT so that their glucose levels can be monitored as a preventive measure.展开更多
In a recent study published in Signal Transduction and Targeted Therapy(doi:10.1038/s41392-022-00964-6),LI et al.used artificial intelligence(AI)to uncover the mechanism behind the interaction between epigenetic alter...In a recent study published in Signal Transduction and Targeted Therapy(doi:10.1038/s41392-022-00964-6),LI et al.used artificial intelligence(AI)to uncover the mechanism behind the interaction between epigenetic alterations and metabolic dysfunction in aging.The team found that the epigenetic alterations of gene ELOVL fatty acid elongase 2(Elovl2)play a crucial role in regulating lipid metabolism,and that impaired Elovl2 function leads to increased endoplasmic reticulum stress and mitochondrial dysfunction,resulting in feature aging phenotypes at both the cellular and physiological levels.The researchers also found that restoring mitochondrial activity could rescue age-related macular degeneration(AMD)phenotypes induced by Elovl2 deficiency in human retinal pigmental epithelial(RPE)cells.Overall,this study reveals an epigenetic-metabolism axis contributing to aging and highlights the potential of AIbased approaches in structure-function studies.展开更多
目的选取无心血管疾病史的上海北部社区老年人群为研究对象,探讨无症状心血管损害与4种不同诊断标准判定的代谢综合征(metabolic syndrome,MS)的关系。方法研究选择1958例无心血管疾病史的老年人群,年龄66.5-73.1岁。MS的定义依据以下标...目的选取无心血管疾病史的上海北部社区老年人群为研究对象,探讨无症状心血管损害与4种不同诊断标准判定的代谢综合征(metabolic syndrome,MS)的关系。方法研究选择1958例无心血管疾病史的老年人群,年龄66.5-73.1岁。MS的定义依据以下标准:2005年美国国家胆固醇教育计划成人治疗专家组第三次会议(National Cholesterol Education Program Adult Treatment PanelⅢ,NCEPⅢ)、国际糖尿病联盟(International Diabetes Federation,IDF)、中华医学会糖尿病学分会(Chinese Diabetes Society,CDS)和中国成人血脂异常防治指南制定联合委员会(Chinese Joint Committee for Developing Chinese Guidelines on Prevention and Treatment of Dyslipidemia in Adults,JCDCG)。无症状心血管损害指标包括测定左心室质量指数、二尖瓣峰值血流速度/舒张早期组织多普勒血流速度、颈股脉搏波传导速度、踝臂指数、动脉斑块和尿白蛋白/肌酐比值。二分类Logistic回归模型用于评价无症状心血管损害与4种不同诊断标准判定的MS之间的相关性。结果(1)NCEPⅢ(2005)、IDF、CDS和ICDCG诊断标准判别的MS患病率分别为46.4%,37.1%,21.6%和28.7%。(2)未校正的Logistic回归分析显示,4种不同诊断标准判定的MS均与左心室肥厚、左心室舒张功能不全、动脉硬化和微量白蛋白尿显著相关(均P<0.01)。(3)在校正了年龄、性别、吸烟和早发心血管疾病家族史后,左心室肥厚、左心室舒张功能不全、动脉硬化和微量白蛋白尿与4种不同诊断标准判定的MS的关联仍存在(均P<0.01)。结论在上海北部社区老年人群中,不同诊断标准判定的MS与无症状心血管损害均密切相关。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
基金National Natural Science Foundation of China,Nos.81771160 (to ZZ),81671060 (to CC),31970973 (to JW),21921004 (to FX)Translational Medicine and In terdisciplinary Research Joint Fund of Zhongnan Hospital of Wuhan University,No.ZNJC201934 (to ZZ)。
文摘Sleep benefits the restoration of energy metabolism and thereby suppo rts neuronal plasticity and cognitive behaviors.Sirt6 is a NAD+-dependent protein deacetylase that has been recognized as an essential regulator of energy metabolism because it modulates various transcriptional regulators and metabolic enzymes.The aim of this study was to investigate the influence of Sirt6 on cerebral function after chronic sleep deprivation(CSD).We assigned C57BL/6J mice to control or two CSD groups and subjected them to AAV2/9-CMV-EGFP or AAV2/9-CMV-Sirt6-EGFP infection in the prelimbic cortex(PrL).We then assessed cerebral functional connectivity(FC) using resting-state functional MRI,neuron/astrocyte metabolism using a metabolic kinetics analysis;dendritic spine densities using sparse-labeling;and miniature excitato ry postsynaptic currents(mEPSCs) and action potential(AP) firing rates using whole-cell patchclamp recordings.In addition,we evaluated cognition via a comprehensive set of behavioral tests.Compared with controls,Sirt6 was significantly decreased(P<0.05) in the PrL after CSD,accompanied by cognitive deficits and decreased FC between the PrL and accumbens nucleus,piriform cortex,motor co rtex,somatosensory co rtex,olfactory tubercle,insular cortex,and cerebellum.Sirt6 ove rexpression reve rsed CSD-induced cognitive impairment and reduced FC.Our analysis of metabolic kinetics using [1-13C] glucose and [2-13C] acetate showed that CSD reduced neuronal Glu4and GABA2synthesis,which could be fully restored via forced Sirt6 expression.Furthermore,Sirt6 ove rexpression reversed CSD-induced decreases in AP firing rates as well as the frequency and amplitude of mEPSCs in PrL pyramidal neurons.These data indicate that Sirt6 can improve cognitive impairment after CSD by regulating the PrL-associated FC network,neuronal glucose metabolism,and glutamatergic neurotransmission.Thus,Sirt6 activation may have potential as a novel strategy for treating sleep disorder-related diseases.
文摘To investigate the effects of impaired glucose metabolism (IGM) on cardiovascular autonomic nervous systems in essential hypertensive (EH) patients by comparing heart rate variability (HRV) and blood pressure variability (BPV) in EH patients with or without type 2 diabetes mellitus (T2DM). Simultaneous 24-h recordings of ambulatory ECG and blood pressure monitoring were performed in 36 male old patients with simple EH and 33 male old patients with EH combined with T2DM. HRV analysis included time domain parameters such as SDNN, SDANN, SDNNi, rMSSD and pNN50, and total spectral power (TP) of HRV, which mainly consists of VLF, LF and HF component along with LF/HF ratio, was also obtained. The value of ambulatory blood pressure was represented as the mean blood pressure (mean systolic/mSBP, diastolic/mDBP and pulse pressure/mPP) during different periods (24 h/24 h, day time/d and night time/n). Standard deviation (SD) as well as coefficient of variance (CV) of blood pressure during each above-mentioned period were obtained to reflect the long-term BPV. Our result showed that SDNN, SDNNi, SDANN, rMSSD, PNN50, TP and HF of HRV in cases of EH with T2DM were all significantly lower than those in simple EH subjects (P〈0.05). No significant differences in VLF or LF was found between the two groups (P〉0.05), while LF/HF ratio was significantly higher in EH with T2DM patients than in simple EH subjects (P〈0.01). Moreover, dmSBP, 24 h-mPP and dmPP were all significantly higher in EH with T2DM patients than in simple EH subjects (P〈0.05), while nmSBP, 24 h-mSBP, 24 h-mDBP, dmDBP, nmDBP or nmPP showed no significant difference between this two groups of patients (P〉0.05). And dSBPSD, dSBPCV and 24 h-SBPSD were all significantly higher in EH with T2DM patients than in simple EH subjects (P〈0.05), while the other BPV indexes showed no significant difference between this two groups (P〉0.05). It is concluded that the cardiovascular autonomic nervous systems in EH patients was further impaired by T2DM, displaying lowering of HRV and enlargement of BPV, which in turn induced abnormal structural and functional changes of cardiovascular systems. Therefore, improving cardiovascular autonomic nervous systems might reduce the occurrence of cardiovascular complications in the EH patients with IGM.
文摘The intestinal microbiota regulates mammalian lipid absorption,metabolism,and storage.We report that the microbiota reprograms intestinal lipid metabolism in mice by repressing the expression of long noncoding RNA(lncRNA)Snhg9(small nucleolar RNA host gene 9)in small intestinal epithelial cells.Snhg9suppressed the activity of peroxisome proliferator-activated receptorγ(PPARγ)-a central regulator of lipid metabolism-by dissociating the PPARγinhibitor sirtuin 1 from cell cycle and apoptosis protein 2(CCAR2).Forced expression ofSnhg9in the intestinal epithelium of conventional mice impaired lipid absorption,reduced body fat,and protected against diet-induced obesity.The microbiota repressedSnhg9expression through an immune relay encompassing myeloid cells and group 3 innate lymphoid cells.Our findings thus identify an unanticipated role for a lncRNA in microbial control of host metabolism.
基金This study was partially supported by an unrestricted grant from Gilead Sciences(CAP-Asia Study-IN-US-989-5334).
文摘Background:Nonalcoholic fatty liver disease(NAFLD)is associated with impaired renal function,and both diseases often occur alongside other metabolic disorders.However,the prevalence and risk factors for impaired renal function in patients with NAFLD remain unclear.The objective of this study was to identify the prevalence and risk factors for renal impairment in NAFLD patients.Methods:All adults aged 18-70 years with ultrasound-diagnosed NAFLD and transient elastography examination from eight Asian centers were enrolled in this prospective study.Liver fibrosis and cirrhosis were assessed by FibroScan-aspartate aminotransferase(FAST),Agile 3+and Agile 4 scores.Impaired renal function and chronic kidney disease(CKD)were defined by an estimated glomerular filtration rate(eGFR)with value of<90 mL/min/1.73 m^(2) and<60 mL/min/1.73 m^(2),respectively,as estimated by the CKD-Epidemiology Collaboration(CKD-EPI)equation.Results:Among 529 included NAFLD patients,the prevalence rates of impaired renal function and CKD were 37.4%and 4.9%,respectively.In multivariate analysis,a moderate-high risk of advanced liver fibrosis and cirrhosis according to Agile 3+and Agile 4 scores were independent risk factors for CKD(P<0.05).Furthermore,increased fasting plasma glucose(FPG)and blood pressure were significantly associated with impaired renal function after controlling for the other components of metabolic syndrome(P<0.05).Compared with patients with normoglycemia,those with prediabetes[FPG≥5.6 mmol/L or hemoglobin A1c(HbA1c)≥5.7%]were more likely to have impaired renal function(P<0.05).Conclusions:Agile 3+and Agile 4 are reliable for identifying NAFLD patients with high risk of CKD.Early glycemic control in the prediabetic stage might have a potential renoprotective role in these patients.
基金supported by a grant of the Romanian National Authority for Scientific Research,project PN-II-PT-PCCA-2011-3,No 80/2012
文摘Alcohol, a widely abused drug, has deleterious effects on the immature nervous system. This study investigates the effect of chronic in vitro ethanol exposure on the metabolism of immature rat cerebellar granular cells(CGCs) and on their response to oxygen-glucose deprivation(OGD). Primary CGC cultures were exposed to ethanol(100 mM in culture medium) or to control ethanol-free medium starting day one in vitro(DIV1). At DIV8, the expression of ATP synthase gene ATP5 g3 was quantified using real-time PCR, then cultures were exposed to 3 hours of OGD or normoxic conditions. Subsequently, cellular metabolism was assessed by a resazurin assay and by ATP level measurement. ATP5 g3 expression was reduced by 12-fold(P = 0.03) and resazurin metabolism and ATP level were decreased to 74.4 ± 4.6% and 55.5 ± 6.9%, respectively after chronic ethanol treatment compared to control values(P < 0.01). Additionally, after OGD exposure of ethanol-treated cultures, resazurin metabolism and ATP level were decreased to 12.7 ± 1.0% and 9.0 ± 2.0% from control values(P < 0.01). These results suggest that chronic ethanol exposure reduces the cellular ATP level, possibly through a gene expression down-regulation mechanism, and increases the vulnerability to oxygen-glucose deprivation. Thus, interventions which improve metabolic function and sustain ATP-levels could attenuate ethanol-induced neuronal dysfunction and should be addressed in future studies.
文摘Anorexia and fasting are host adaptations to acute infection, inducing a metabolic switch towards ketogenesis and the production of ketone bodies, including β-hydroxybutyrate (BHB) 1-6. However, whether ketogenesis metabolically influences the immune response in pulmonary infections remains unclear. Here we report impaired production of BHB in humans with SARS-CoV-2-induced but not influenza-induced acute respiratory distress syndrome (ARDS). CD4^(+) T cell function is impaired in COVID-19 and BHB promotes both survival and production of Interferon-γ from CD4^(+) T cells. Using metabolic tracing analysis, we uncovered that BHB provides an alternative carbon source to fuel oxidative phosphorylation (OXPHOS) and the production of bioenergetic amino acids and glutathione, which is important for maintaining the redox balance. T cells from patients with SARS-CoV-2-induced ARDS were exhausted and skewed towards glycolysis, but can be metabolically reprogrammed by BHB to perform OXPHOS, thereby increasing their functionality.
文摘AIM:To investigate whether impaired fasting glucose(IFG)confers cardiovascular risk.METHODS:A non-diabetic population-based sample representative of middle-aged and elderly Turks was studied at 8.5 years’follow-up for incident diabetes and coronary heart disease(CHD).Metabolic syndrome(MetS)was defined by ATP-Ⅲcriteria modifiedfor male abdominal obesity,and IFG and type 2 diabetes were identified by criteria of the American Diabetes Association.Stratification by presence of MetS was used.Outcomes were predicted providing estimates for hazard ratio(HR)obtained by use of Cox proportional hazards regression analysis in models that controlled for potential confounders.RESULTS:In 3181 adults(aged 52±11.5 years at baseline),analysis stratified by MetS,gender and IFG status distinguished normoglycemic subjects by a"hypertriglyceridemic waist"phenotype consisting of significantly higher waist circumference,fasting triglyceride and lower high-density lipoprotein-cholesterol,regardless of gender and MetS.Additionally,lipoprotein(Lp)(a)tended to be lower in(especially female)participants with MetS.Multivariable linear regression in a subset of the sample demonstrated decreased Lp(a)levels to be associated with increased fasting glucose and insulin concentrations,again particularly in women.In Cox regression analysis,compared with normoglycemia,baseline IFG adjusted for major confounders significantly predicted incident diabetes at a 3-fold HR in men and only women with MetS.Cox models for developing CHD in 339 individuals,adjusted for conventional risk factors,revealed that IFG status protected against CHD risk[HR=0.37(95%CI:0.14-0.998)]in subjects free of MetS,a protection that attenuated partly in male and fully in female participants with MetS.CONCLUSION:IFG status in non-diabetic people without MetS displays reduced future CHD risk,yet is modulated by MetS,likely due to autoimmune activation linked to serum Lp(a).
文摘Objective :To investigate glucose metabolism in women with multiple ovarian follicles (MOF) and explore the relationship between glucose metabolism, insulin resistance and body weight. Methods:We evaluated 46 women with MFO and 30 normal women as controls. All the subjects were given 75g of glucose orally in order to perform the oral glucose tolerance test (OGTT) and insulin releasing test (IRT), and they were also evaluated for insulin resistance using the insulin resistance index with homeostatic model assessment (HOMA). Results:The occurrence of impaired glucose tolerance in women with MOF was 10.87%, which was significantly higher than that in the control group (3.33% ,P 〈 0.05). The rate of insulin resistance was 30.43% in the study group as compared to 10.00% in the control group. The results showed that there was significant difference between the two groups(P 〈 0.05). The levels of FSH,LH,PRL,E2,T and P between the two groups had no significant difference (P 〉 0.05). BMI in women with impaired glucose tolerance was correlated positively to insulin resistance (r = 0.567, P 〈 0.05). Conclusion:Abnormal glucose metabolism was observed in women with unitary multiple ovarian follicles, and this could be attributed to obesity and insulin resistance. Women with MOF and associated obesity should be subjected to OGTT so that their glucose levels can be monitored as a preventive measure.
文摘In a recent study published in Signal Transduction and Targeted Therapy(doi:10.1038/s41392-022-00964-6),LI et al.used artificial intelligence(AI)to uncover the mechanism behind the interaction between epigenetic alterations and metabolic dysfunction in aging.The team found that the epigenetic alterations of gene ELOVL fatty acid elongase 2(Elovl2)play a crucial role in regulating lipid metabolism,and that impaired Elovl2 function leads to increased endoplasmic reticulum stress and mitochondrial dysfunction,resulting in feature aging phenotypes at both the cellular and physiological levels.The researchers also found that restoring mitochondrial activity could rescue age-related macular degeneration(AMD)phenotypes induced by Elovl2 deficiency in human retinal pigmental epithelial(RPE)cells.Overall,this study reveals an epigenetic-metabolism axis contributing to aging and highlights the potential of AIbased approaches in structure-function studies.
文摘目的选取无心血管疾病史的上海北部社区老年人群为研究对象,探讨无症状心血管损害与4种不同诊断标准判定的代谢综合征(metabolic syndrome,MS)的关系。方法研究选择1958例无心血管疾病史的老年人群,年龄66.5-73.1岁。MS的定义依据以下标准:2005年美国国家胆固醇教育计划成人治疗专家组第三次会议(National Cholesterol Education Program Adult Treatment PanelⅢ,NCEPⅢ)、国际糖尿病联盟(International Diabetes Federation,IDF)、中华医学会糖尿病学分会(Chinese Diabetes Society,CDS)和中国成人血脂异常防治指南制定联合委员会(Chinese Joint Committee for Developing Chinese Guidelines on Prevention and Treatment of Dyslipidemia in Adults,JCDCG)。无症状心血管损害指标包括测定左心室质量指数、二尖瓣峰值血流速度/舒张早期组织多普勒血流速度、颈股脉搏波传导速度、踝臂指数、动脉斑块和尿白蛋白/肌酐比值。二分类Logistic回归模型用于评价无症状心血管损害与4种不同诊断标准判定的MS之间的相关性。结果(1)NCEPⅢ(2005)、IDF、CDS和ICDCG诊断标准判别的MS患病率分别为46.4%,37.1%,21.6%和28.7%。(2)未校正的Logistic回归分析显示,4种不同诊断标准判定的MS均与左心室肥厚、左心室舒张功能不全、动脉硬化和微量白蛋白尿显著相关(均P<0.01)。(3)在校正了年龄、性别、吸烟和早发心血管疾病家族史后,左心室肥厚、左心室舒张功能不全、动脉硬化和微量白蛋白尿与4种不同诊断标准判定的MS的关联仍存在(均P<0.01)。结论在上海北部社区老年人群中,不同诊断标准判定的MS与无症状心血管损害均密切相关。
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.