Although the structural and functional effects of exercise on the heart are well established,the metabolic changes that occur in the heart during and after exercise remain unclear.In this study,we used metabolomics to...Although the structural and functional effects of exercise on the heart are well established,the metabolic changes that occur in the heart during and after exercise remain unclear.In this study,we used metabolomics to assess time-dependent changes in the murine cardiac metabolome following 1 session of treadmill exercise.After the exercise bout,we also recorded blood lactate,glucose,and ketone body levels and measured cardiac mitochondrial respiration.In both male and female mice,moderate-and high-intensity exercise acutely increased blood lactate levels.In both sexes,low-and moderate-intensity exercise augmented circulating 3-hydroxybutryrate levels immediately after the exercise bout;however,only in female mice did high-intensity exercise increase 3-hydroxybutyrate levels,with significant increases occurring 1 h after the exercise session.Untargeted metabolomics analyses of sedentary female and male hearts suggest considerable sex-dependent differences in basal cardiac metabolite levels,with female hearts characterized by higher levels of pantothenate,pyridoxamine,homoarginine,tryptophan,and several glycerophospholipid and sphingomyelin species and lower levels of numerous metabolites,including acetyl coenzyme A,glucuronate,gulonate,hydroxyproline,prolyl-hydroxyproline,carnosine,anserine,and carnitinylated and glycinated species,as compared with male hearts.Immediately after a bout of treadmill exercise,both male and female hearts had higher levels of corticosterone;however,female mice showed more extensive exercise-induced changes in the cardiac metabolome,characterized by significant,time-dependent changes in amino acids(e.g.,serine,alanine,tyrosine,tryptophan,branched-chain amino acids)and the ketone body 3-hydroxybutyrate.Results from experiments using isolated cardiac mitochondria suggest that high-intensity treadmill exercise does not acutely affect respiration or mitochondrial coupling;however,female cardiac mitochondria demonstrate generally higher adenosine diphosphate sensitivity compared with male cardiac mitochondria.Collectively,these findings in mice reveal key sex-dependent differences in cardiac metabolism and suggest that the metabolic network in the female heart is more responsive to physiological stress caused by exercise.展开更多
Polycyclic aromatic hydrocarbons (PAHs) are formed due to natural and anthropogenic activities and known for their potential impact and persistence in the environment. PAHs exposure has been linked to cause adverse he...Polycyclic aromatic hydrocarbons (PAHs) are formed due to natural and anthropogenic activities and known for their potential impact and persistence in the environment. PAHs exposure has been linked to cause adverse health effect including lung cancer, heart conditions and genetic mutations. The understanding of metabolic effects of PAHs exposure is less clear especially in the presence of pro-inflammatory stress like alcoholism or diabetes. The aim of this article is to understand the metabolic effects of PAHs exposure on Type 2 Diabetes Mellitus (T2DM) by analyzing the clinical biomarkers data retrieved from the National Health and Nutrition Examination Survey, Center for Disease Control (CDC NHANES) (2015-16). This study has also accessed the interactive impact of PAHs and other proinflammatory factors, like alcohol intake on the metabolic syndrome on T2DM. We investigated urinary levels of hydroxylated PAHs metabolites (OH-PAHs) along with demographic, clinical and laboratory data. Generalize linear model Univariate factorial ANOVA was used to evaluate the group differences in the demographics, PAH exposure, drinking patterns, clinical data, and biomarker levels. Linear regression model was used to analyze the association of biomarkers, PAH exposure and drinking data. Multivariable regression model was used for multi-independent model to assess comorbidity association and their effect sizes on the clinical outcomes. The results indicated that BMI (p = 0.002), and age (≤0.001) are independent demographic risk factors for T2DM in high PAHs exposure. Acute proinflammatory activity characterized by CRP, is augmented by elevated monocyte levels (p ≤ 0.001) and stepwise addition of 1-Hydroxynapthelene (p = 0.005), and 2-Hydroxynapthelene (p = 0.001) independently. Prevalence of highest average drinks over time is observed in the high PAHs exposure;with males drinking almost twice compared to females in highly exposed population. Pathway response of T2DM shows sexual dimorphism;with males showing association with triglycerides (p ≤ 0.001), and females with CRP (p = 0.015) independently with HbA1C. The arrangement of CRP, absolute monocyte levels, serum triglycerides and average drinks over time predict the HbA1C levels (adjusted R2 = 0.226, p ≤ 0.001) in individuals with high PAHs exposure. Findings from this investigation support the pathological role of high exposure of PAHs in the exacerbation of metabolic disorder syndrome involving T2DM. Sexual dimorphism is reflected in alcohol drinking, with males drinking more in the high PAHs exposure group. Alcohol drinking as an independent factor was associated with the T2DM indicator, HbA1C in individuals with high PAHs exposure.展开更多
Although testing wastewater for public health surveillance has recently received significant attention in the United States,researchers and public health professionals have long realized the tremendous promise of envi...Although testing wastewater for public health surveillance has recently received significant attention in the United States,researchers and public health professionals have long realized the tremendous promise of environmental surveillance(ES),defined as tracking pathogens of interest in fecally contaminated surface waters,soil,or fomites,in low-resource settings for public health action.1,2 The power of ES in lowresource settings is most clearly illustrated with the over 30 years of well-established and standardized polio surveillance.As part of the Global Polio Eradication Initiative,the World Health Organization(WHO)has accredited 146 laboratories within the Global Polio Lab Network(GPLN).These facilities across 92 countries process over 8,000 wastewater or fecally contaminated surface water samples per year,in addition to over 220,000 stool samples annually.3 The data generated from the GPLN are closely linked to clear public health action related to targeted vaccination campaigns.The investment and adoption of ES for polio eradication efforts serves as a use-case for other targets of interest.To explore the current state of the field,the National Science Foundation-funded Research Coordination Network(RCN)on Wastewater Based Epidemiology for SARS-CoV-2 and Emerging Public Health Threats held a workshop in December 2023 to discuss the opportunities and challenges for ES in low-resource settings(Figure 1).Discussions during the workshop highlighted knowledge gaps,best-practices,target selection,academic/government/private partnerships and overall public health action and sustainability of these programs.展开更多
基金Supported in part by grants from the NIH (HL154663, HL147844,HL130174,HL078825,GM127607)supported by the Jewish Heritage Fund for Excellence.
文摘Although the structural and functional effects of exercise on the heart are well established,the metabolic changes that occur in the heart during and after exercise remain unclear.In this study,we used metabolomics to assess time-dependent changes in the murine cardiac metabolome following 1 session of treadmill exercise.After the exercise bout,we also recorded blood lactate,glucose,and ketone body levels and measured cardiac mitochondrial respiration.In both male and female mice,moderate-and high-intensity exercise acutely increased blood lactate levels.In both sexes,low-and moderate-intensity exercise augmented circulating 3-hydroxybutryrate levels immediately after the exercise bout;however,only in female mice did high-intensity exercise increase 3-hydroxybutyrate levels,with significant increases occurring 1 h after the exercise session.Untargeted metabolomics analyses of sedentary female and male hearts suggest considerable sex-dependent differences in basal cardiac metabolite levels,with female hearts characterized by higher levels of pantothenate,pyridoxamine,homoarginine,tryptophan,and several glycerophospholipid and sphingomyelin species and lower levels of numerous metabolites,including acetyl coenzyme A,glucuronate,gulonate,hydroxyproline,prolyl-hydroxyproline,carnosine,anserine,and carnitinylated and glycinated species,as compared with male hearts.Immediately after a bout of treadmill exercise,both male and female hearts had higher levels of corticosterone;however,female mice showed more extensive exercise-induced changes in the cardiac metabolome,characterized by significant,time-dependent changes in amino acids(e.g.,serine,alanine,tyrosine,tryptophan,branched-chain amino acids)and the ketone body 3-hydroxybutyrate.Results from experiments using isolated cardiac mitochondria suggest that high-intensity treadmill exercise does not acutely affect respiration or mitochondrial coupling;however,female cardiac mitochondria demonstrate generally higher adenosine diphosphate sensitivity compared with male cardiac mitochondria.Collectively,these findings in mice reveal key sex-dependent differences in cardiac metabolism and suggest that the metabolic network in the female heart is more responsive to physiological stress caused by exercise.
文摘Polycyclic aromatic hydrocarbons (PAHs) are formed due to natural and anthropogenic activities and known for their potential impact and persistence in the environment. PAHs exposure has been linked to cause adverse health effect including lung cancer, heart conditions and genetic mutations. The understanding of metabolic effects of PAHs exposure is less clear especially in the presence of pro-inflammatory stress like alcoholism or diabetes. The aim of this article is to understand the metabolic effects of PAHs exposure on Type 2 Diabetes Mellitus (T2DM) by analyzing the clinical biomarkers data retrieved from the National Health and Nutrition Examination Survey, Center for Disease Control (CDC NHANES) (2015-16). This study has also accessed the interactive impact of PAHs and other proinflammatory factors, like alcohol intake on the metabolic syndrome on T2DM. We investigated urinary levels of hydroxylated PAHs metabolites (OH-PAHs) along with demographic, clinical and laboratory data. Generalize linear model Univariate factorial ANOVA was used to evaluate the group differences in the demographics, PAH exposure, drinking patterns, clinical data, and biomarker levels. Linear regression model was used to analyze the association of biomarkers, PAH exposure and drinking data. Multivariable regression model was used for multi-independent model to assess comorbidity association and their effect sizes on the clinical outcomes. The results indicated that BMI (p = 0.002), and age (≤0.001) are independent demographic risk factors for T2DM in high PAHs exposure. Acute proinflammatory activity characterized by CRP, is augmented by elevated monocyte levels (p ≤ 0.001) and stepwise addition of 1-Hydroxynapthelene (p = 0.005), and 2-Hydroxynapthelene (p = 0.001) independently. Prevalence of highest average drinks over time is observed in the high PAHs exposure;with males drinking almost twice compared to females in highly exposed population. Pathway response of T2DM shows sexual dimorphism;with males showing association with triglycerides (p ≤ 0.001), and females with CRP (p = 0.015) independently with HbA1C. The arrangement of CRP, absolute monocyte levels, serum triglycerides and average drinks over time predict the HbA1C levels (adjusted R2 = 0.226, p ≤ 0.001) in individuals with high PAHs exposure. Findings from this investigation support the pathological role of high exposure of PAHs in the exacerbation of metabolic disorder syndrome involving T2DM. Sexual dimorphism is reflected in alcohol drinking, with males drinking more in the high PAHs exposure group. Alcohol drinking as an independent factor was associated with the T2DM indicator, HbA1C in individuals with high PAHs exposure.
基金supported by the National Science Foundation,grant 2202361.
文摘Although testing wastewater for public health surveillance has recently received significant attention in the United States,researchers and public health professionals have long realized the tremendous promise of environmental surveillance(ES),defined as tracking pathogens of interest in fecally contaminated surface waters,soil,or fomites,in low-resource settings for public health action.1,2 The power of ES in lowresource settings is most clearly illustrated with the over 30 years of well-established and standardized polio surveillance.As part of the Global Polio Eradication Initiative,the World Health Organization(WHO)has accredited 146 laboratories within the Global Polio Lab Network(GPLN).These facilities across 92 countries process over 8,000 wastewater or fecally contaminated surface water samples per year,in addition to over 220,000 stool samples annually.3 The data generated from the GPLN are closely linked to clear public health action related to targeted vaccination campaigns.The investment and adoption of ES for polio eradication efforts serves as a use-case for other targets of interest.To explore the current state of the field,the National Science Foundation-funded Research Coordination Network(RCN)on Wastewater Based Epidemiology for SARS-CoV-2 and Emerging Public Health Threats held a workshop in December 2023 to discuss the opportunities and challenges for ES in low-resource settings(Figure 1).Discussions during the workshop highlighted knowledge gaps,best-practices,target selection,academic/government/private partnerships and overall public health action and sustainability of these programs.
