Pub Date : 2024-11-08DOI: 10.1038/s44324-024-00037-y
Sophiya L. Sims, Hilaree N. Frazier, Sami L. Case, Ruei-Lung Lin, James N. Trosper, Hemendra J. Vekaria, Patrick G. Sullivan, Olivier Thibault
Energy flow within cellular elements of the brain is a well-orchestrated, tightly regulated process, however, details underlying these functions at the single-cell level are still poorly understood. Studying hypometabolism in aging and neurodegenerative diseases may benefit from experimentation on unicellular bioenergetics. Here, we examined energy status in neurons and astrocytes using mixed hippocampal cultures and PercevalHR, an ATP:ADP nanosensor. We assessed exposures of several compounds including KCl, glutamate, FCCP, insulin, and glucose. A mitochondrial stress test was performed, and PercevalHR’s fluorescence was corrected for pH using pHrodo. Results demonstrate that PercevalHR can reliably report on the energetic status of two cell types that communicate in a mixed-culture setting. While KCl, glutamate, and FCCP showed clear changes in PercevalHR fluorescence, insulin and glucose responses were found to be more subtle and sensitive to extracellular glucose. These results may highlight mechanisms that mediate insulin sensitivity in the brain.
{"title":"Variable bioenergetic sensitivity of neurons and astrocytes to insulin and extracellular glucose","authors":"Sophiya L. Sims, Hilaree N. Frazier, Sami L. Case, Ruei-Lung Lin, James N. Trosper, Hemendra J. Vekaria, Patrick G. Sullivan, Olivier Thibault","doi":"10.1038/s44324-024-00037-y","DOIUrl":"10.1038/s44324-024-00037-y","url":null,"abstract":"Energy flow within cellular elements of the brain is a well-orchestrated, tightly regulated process, however, details underlying these functions at the single-cell level are still poorly understood. Studying hypometabolism in aging and neurodegenerative diseases may benefit from experimentation on unicellular bioenergetics. Here, we examined energy status in neurons and astrocytes using mixed hippocampal cultures and PercevalHR, an ATP:ADP nanosensor. We assessed exposures of several compounds including KCl, glutamate, FCCP, insulin, and glucose. A mitochondrial stress test was performed, and PercevalHR’s fluorescence was corrected for pH using pHrodo. Results demonstrate that PercevalHR can reliably report on the energetic status of two cell types that communicate in a mixed-culture setting. While KCl, glutamate, and FCCP showed clear changes in PercevalHR fluorescence, insulin and glucose responses were found to be more subtle and sensitive to extracellular glucose. These results may highlight mechanisms that mediate insulin sensitivity in the brain.","PeriodicalId":501710,"journal":{"name":"npj Metabolic Health and Disease","volume":" ","pages":"1-13"},"PeriodicalIF":0.0,"publicationDate":"2024-11-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s44324-024-00037-y.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142595705","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-11-06DOI: 10.1038/s44324-024-00033-2
Nicola M. Sergienko, Adam J. Trewin, Helen Kiriazis, Antonia J. A. Raaijmakers, Daniel G. Donner, Victoria C. Garside, Kelly A. Smith, James R. Bell, Kimberley M. Mellor, Lea M. D. Delbridge, Julie R. McMullen, Kate L. Weeks
Protein phosphatase 2A (PP2A) regulatory subunit B55α has been implicated in the transcriptional regulation of cardiac growth and fibrosis by suppressing HDAC5/MEF2 signalling in cardiomyocytes. We created and characterised two mouse models with global or cardiomyocyte-specific disruption of the gene encoding B55α (Ppp2r2a) to conduct the first detailed exploration of B55α in the heart. Global homozygous B55α knockout mice died in utero, while heterozygous mice had thinner left ventricular walls at 12 months, an effect more pronounced in males. At 10–12 weeks of age, cardiomyocyte-specific B55α knockout mice displayed normal cardiac morphology with increased left ventricular collagen deposition, identifying B55α as a negative regulator of cardiac fibrosis. Gene expression analyses demonstrated extensive remodelling of the cardiac transcriptome in male but not female mice, revealing a sexually dimorphic role for B55α in cardiac transcriptional regulation. These findings provide a basis for future work investigating B55α in cardiac stress settings.
{"title":"Sex-specific regulation of the cardiac transcriptome by the protein phosphatase 2A regulatory subunit B55α","authors":"Nicola M. Sergienko, Adam J. Trewin, Helen Kiriazis, Antonia J. A. Raaijmakers, Daniel G. Donner, Victoria C. Garside, Kelly A. Smith, James R. Bell, Kimberley M. Mellor, Lea M. D. Delbridge, Julie R. McMullen, Kate L. Weeks","doi":"10.1038/s44324-024-00033-2","DOIUrl":"10.1038/s44324-024-00033-2","url":null,"abstract":"Protein phosphatase 2A (PP2A) regulatory subunit B55α has been implicated in the transcriptional regulation of cardiac growth and fibrosis by suppressing HDAC5/MEF2 signalling in cardiomyocytes. We created and characterised two mouse models with global or cardiomyocyte-specific disruption of the gene encoding B55α (Ppp2r2a) to conduct the first detailed exploration of B55α in the heart. Global homozygous B55α knockout mice died in utero, while heterozygous mice had thinner left ventricular walls at 12 months, an effect more pronounced in males. At 10–12 weeks of age, cardiomyocyte-specific B55α knockout mice displayed normal cardiac morphology with increased left ventricular collagen deposition, identifying B55α as a negative regulator of cardiac fibrosis. Gene expression analyses demonstrated extensive remodelling of the cardiac transcriptome in male but not female mice, revealing a sexually dimorphic role for B55α in cardiac transcriptional regulation. These findings provide a basis for future work investigating B55α in cardiac stress settings.","PeriodicalId":501710,"journal":{"name":"npj Metabolic Health and Disease","volume":" ","pages":"1-13"},"PeriodicalIF":0.0,"publicationDate":"2024-11-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s44324-024-00033-2.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142595719","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-11-06DOI: 10.1038/s44324-024-00030-5
Irene Caruso, Angelo Cignarelli, Gian Pio Sorice, Sebastio Perrini, Francesco Giorgino
Obesity-related disability-adjusted life years (DALYs) are expected to increase by approximately 40% from 2020 to 2030. DALYs and mortality related to obesity are the consequence of multiple comorbidities such as cardiovascular (i.e., heart failure) and metabolic diseases (i.e. type 2 diabetes [T2D], metabolic dysfunction-associated steatotic liver disease [MASLD]). Lifestyle interventions represent the foundation of obesity treatment, yet an escalation to pharmacological and/or surgical interventions is often needed. Liraglutide, semaglutide and tirzepatide are incretin-based therapies currently approved by FDA for the management of obesity, while triple GIPR/GCGR/GLP-1R agonist retatrutide (LY3437943), the cagrilintide/semaglutide (CagriSema) 2.4 mg combination, high-dose oral semaglutide, and oral orforglipron are in advanced stages of development. Incretin-based therapies have been associated with a body weight (BW) reduction of ≥5% in at least half of patients in most randomized controlled trials (RCT) and real-world studies (RWS). Semaglutide and tirzepatide have also displayed a mean 60–69% 10-years relative risk reduction of T2D development. In line with evidence accrued in patients with T2D, incretin-based therapies produced a favorable effect on traditional cardiovascular risk factors, such as lipids and blood pressure, and even reduced the risk of major cardiovascular events and heart failure-related events in individuals with obesity, as recently demonstrated for the first time in the SELECT trial with semaglutide 2.4 mg once-weekly. Moreover, incretin-based therapies have also been proven beneficial on obesity-related comorbidities, such as knee osteoarthritis (KOA), obstructive sleep apnea (OSA) syndrome, and MASLD. Further research is needed to improve our understanding of their effects on obesity-related comorbidities and the underlying mechanism, whether involving direct effects on target tissues or mediated by improvement in BW, glucose levels and other CV risk factors.
{"title":"Incretin-based therapies for the treatment of obesity-related diseases","authors":"Irene Caruso, Angelo Cignarelli, Gian Pio Sorice, Sebastio Perrini, Francesco Giorgino","doi":"10.1038/s44324-024-00030-5","DOIUrl":"10.1038/s44324-024-00030-5","url":null,"abstract":"Obesity-related disability-adjusted life years (DALYs) are expected to increase by approximately 40% from 2020 to 2030. DALYs and mortality related to obesity are the consequence of multiple comorbidities such as cardiovascular (i.e., heart failure) and metabolic diseases (i.e. type 2 diabetes [T2D], metabolic dysfunction-associated steatotic liver disease [MASLD]). Lifestyle interventions represent the foundation of obesity treatment, yet an escalation to pharmacological and/or surgical interventions is often needed. Liraglutide, semaglutide and tirzepatide are incretin-based therapies currently approved by FDA for the management of obesity, while triple GIPR/GCGR/GLP-1R agonist retatrutide (LY3437943), the cagrilintide/semaglutide (CagriSema) 2.4 mg combination, high-dose oral semaglutide, and oral orforglipron are in advanced stages of development. Incretin-based therapies have been associated with a body weight (BW) reduction of ≥5% in at least half of patients in most randomized controlled trials (RCT) and real-world studies (RWS). Semaglutide and tirzepatide have also displayed a mean 60–69% 10-years relative risk reduction of T2D development. In line with evidence accrued in patients with T2D, incretin-based therapies produced a favorable effect on traditional cardiovascular risk factors, such as lipids and blood pressure, and even reduced the risk of major cardiovascular events and heart failure-related events in individuals with obesity, as recently demonstrated for the first time in the SELECT trial with semaglutide 2.4 mg once-weekly. Moreover, incretin-based therapies have also been proven beneficial on obesity-related comorbidities, such as knee osteoarthritis (KOA), obstructive sleep apnea (OSA) syndrome, and MASLD. Further research is needed to improve our understanding of their effects on obesity-related comorbidities and the underlying mechanism, whether involving direct effects on target tissues or mediated by improvement in BW, glucose levels and other CV risk factors.","PeriodicalId":501710,"journal":{"name":"npj Metabolic Health and Disease","volume":" ","pages":"1-14"},"PeriodicalIF":0.0,"publicationDate":"2024-11-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s44324-024-00030-5.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142595724","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-10-18DOI: 10.1038/s44324-024-00035-0
Lubayna S. Elahi, Michael C. Condro, Riki Kawaguchi, Yue Qin, Alvaro G. Alvarado, Brandon Gruender, Haocheng Qi, Tie Li, Albert Lai, Maria G. Castro, Pedro R. Lowenstein, Matthew C. Garrett, Harley I. Kornblum
{"title":"Publisher Correction: Valproic acid targets IDH1 mutants through alteration of lipid metabolism","authors":"Lubayna S. Elahi, Michael C. Condro, Riki Kawaguchi, Yue Qin, Alvaro G. Alvarado, Brandon Gruender, Haocheng Qi, Tie Li, Albert Lai, Maria G. Castro, Pedro R. Lowenstein, Matthew C. Garrett, Harley I. Kornblum","doi":"10.1038/s44324-024-00035-0","DOIUrl":"10.1038/s44324-024-00035-0","url":null,"abstract":"","PeriodicalId":501710,"journal":{"name":"npj Metabolic Health and Disease","volume":" ","pages":"1-1"},"PeriodicalIF":0.0,"publicationDate":"2024-10-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s44324-024-00035-0.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142447895","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-10-11DOI: 10.1038/s44324-024-00029-y
Kyle Fulghum, Sebastian F. Salathe, Xin Davis, John P. Thyfault, Patrycja Puchalska, Peter A. Crawford
Cardiometabolic complications of obesity present a growing public health concern and are associated with poor outcomes, mediated in part by an increased risk for cardiovascular disease, metabolic dysfunction-associated fatty liver disease, and systemic insulin resistance. Recent studies support that both insulin resistance and obesity are also associated with aberrant brain metabolism and cognitive impairment similar to what is observed in neurodegenerative diseases. Central to these pathological outcomes are adverse changes in tissue glucose and ketone body metabolism, suggesting that regulation of substrate utilization could be a mechanistic link between the cardiometabolic outcomes of obesity and the progression of cognitive decline. Here, we review ketone body metabolism in physiological and pathological conditions with an emphasis on the therapeutic potential of ketone bodies in treating cardiometabolic diseases and neurodegenerative diseases that lead to cognitive decline. We highlight recent findings in the associations among cardiometabolic disease, ketone body metabolism, and cognitive health while providing a theoretical framework by which ketone bodies may promote positive health outcomes and preserve cognitive function.
{"title":"Ketone body metabolism and cardiometabolic implications for cognitive health","authors":"Kyle Fulghum, Sebastian F. Salathe, Xin Davis, John P. Thyfault, Patrycja Puchalska, Peter A. Crawford","doi":"10.1038/s44324-024-00029-y","DOIUrl":"10.1038/s44324-024-00029-y","url":null,"abstract":"Cardiometabolic complications of obesity present a growing public health concern and are associated with poor outcomes, mediated in part by an increased risk for cardiovascular disease, metabolic dysfunction-associated fatty liver disease, and systemic insulin resistance. Recent studies support that both insulin resistance and obesity are also associated with aberrant brain metabolism and cognitive impairment similar to what is observed in neurodegenerative diseases. Central to these pathological outcomes are adverse changes in tissue glucose and ketone body metabolism, suggesting that regulation of substrate utilization could be a mechanistic link between the cardiometabolic outcomes of obesity and the progression of cognitive decline. Here, we review ketone body metabolism in physiological and pathological conditions with an emphasis on the therapeutic potential of ketone bodies in treating cardiometabolic diseases and neurodegenerative diseases that lead to cognitive decline. We highlight recent findings in the associations among cardiometabolic disease, ketone body metabolism, and cognitive health while providing a theoretical framework by which ketone bodies may promote positive health outcomes and preserve cognitive function.","PeriodicalId":501710,"journal":{"name":"npj Metabolic Health and Disease","volume":" ","pages":"1-13"},"PeriodicalIF":0.0,"publicationDate":"2024-10-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s44324-024-00029-y.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142435925","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-10-04DOI: 10.1038/s44324-024-00026-1
Linda T. Nguyen, Garron T. Dodd
Metabolic diseases such as obesity and type 2 diabetes affect >2 billion people worldwide, yet there are currently no effective treatments to promote remission of disease. It is therefore critical to understand the physiological and pathophysiological mechanisms underlying metabolic disease, to drive the development of effective therapeutics. Whilst the majority of research over the past few decades has focused on neurons in the hypothalamus, there is growing evidence that non-neuronal glial cells in this region play a substantial role in regulating metabolism. Here, we provide an overview of the current dogmatic view of the neuroendocrine axis governing metabolism and update this neuron-centric view to include emerging evidence implicating glial cells including tanycytes, astrocytes, microglia, and oligodendrocyte lineage cells. We discuss the latest research implicating glia in hormone transport and hypothalamic inflammation, highlighting these cells as key contributors to metabolic control and dysfunction. Glial cells therefore offer new cellular and molecular targets for future therapeutic design, to tackle metabolic disease treatment from a new perspective.
{"title":"Hypothalamic neuronal-glial crosstalk in metabolic disease","authors":"Linda T. Nguyen, Garron T. Dodd","doi":"10.1038/s44324-024-00026-1","DOIUrl":"10.1038/s44324-024-00026-1","url":null,"abstract":"Metabolic diseases such as obesity and type 2 diabetes affect >2 billion people worldwide, yet there are currently no effective treatments to promote remission of disease. It is therefore critical to understand the physiological and pathophysiological mechanisms underlying metabolic disease, to drive the development of effective therapeutics. Whilst the majority of research over the past few decades has focused on neurons in the hypothalamus, there is growing evidence that non-neuronal glial cells in this region play a substantial role in regulating metabolism. Here, we provide an overview of the current dogmatic view of the neuroendocrine axis governing metabolism and update this neuron-centric view to include emerging evidence implicating glial cells including tanycytes, astrocytes, microglia, and oligodendrocyte lineage cells. We discuss the latest research implicating glia in hormone transport and hypothalamic inflammation, highlighting these cells as key contributors to metabolic control and dysfunction. Glial cells therefore offer new cellular and molecular targets for future therapeutic design, to tackle metabolic disease treatment from a new perspective.","PeriodicalId":501710,"journal":{"name":"npj Metabolic Health and Disease","volume":" ","pages":"1-14"},"PeriodicalIF":0.0,"publicationDate":"2024-10-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s44324-024-00026-1.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142397585","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-10-04DOI: 10.1038/s44324-024-00032-3
M. K. Montgomery
{"title":"Putting metabolism centre stage in health and disease","authors":"M. K. Montgomery","doi":"10.1038/s44324-024-00032-3","DOIUrl":"10.1038/s44324-024-00032-3","url":null,"abstract":"","PeriodicalId":501710,"journal":{"name":"npj Metabolic Health and Disease","volume":" ","pages":"1-2"},"PeriodicalIF":0.0,"publicationDate":"2024-10-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s44324-024-00032-3.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142397606","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-10-03DOI: 10.1038/s44324-024-00025-2
Benjamin D. Horne, Jeffrey L. Anderson, Heidi T. May, Tami L. Bair, Viet T. Le, Leslie Iverson, Kirk U. Knowlton, Joseph B. Muhlestein
Intense intermittent fasting regimens safely reduce weight to a similar extent as caloric restriction. A previous trial reported low-frequency 26-week intermittent fasting reduced homeostatic model assessment of insulin resistance (HOMA-IR) without significant weight loss. During fasting, human growth hormone (HGH) increases substantially, but whether basal HGH modifies the effect of fasting on outcomes of repeated fasting is unknown. In a post hoc analysis of a randomized controlled trial (registration: clinicaltrials.gov, NCT02770313, May 12, 2016), subjects (N = 68) were adults ages 21–70 years with modest cholesterol elevation, ≥1 metabolic syndrome component, available HGH measurements, no chronic disease, and no statin or anti-diabetes medication. Randomization was 1:1 to intermittent fasting (24-hour, water-only, twice-per-week for 4 weeks, then once-per-week for 22 weeks) or 26-week ad libitum control. General linear modeling evaluated the interaction of trial arm with baseline HGH for HOMA-IR changes. Subjects with lower baseline HGH had 26-week HOMA-IR changes (p = 0.003) of −1.04 ± 0.99 for fasting versus 0.60 ± 1.04 for controls. Subjects with higher baseline HGH had HOMA-IR changes (p = 0.26) of −0.69 ± 0.75 (fasting) and −0.42 ± 0.92 (controls). The interaction of fasting with lower baseline HGH was significant (p-interaction=0.004). Results were similar for insulin and glucose. Weight loss at 26 weeks was not significantly different between fasting and controls (−1.74 ± 4.81 kg vs. 0.21 ± 3.50 kg, p = 0.08) and was not correlated with changes in HOMA-IR, insulin, glucose, and HGH. In conclusion, lower baseline HGH modified the effect of low-frequency water-only 24-hour fasting in profoundly reducing HOMA-IR over 26 weeks compared both to controls and to fasting subjects with higher baseline HGH.
{"title":"Insulin resistance reduction, intermittent fasting, and human growth hormone: secondary analysis of a randomized trial","authors":"Benjamin D. Horne, Jeffrey L. Anderson, Heidi T. May, Tami L. Bair, Viet T. Le, Leslie Iverson, Kirk U. Knowlton, Joseph B. Muhlestein","doi":"10.1038/s44324-024-00025-2","DOIUrl":"10.1038/s44324-024-00025-2","url":null,"abstract":"Intense intermittent fasting regimens safely reduce weight to a similar extent as caloric restriction. A previous trial reported low-frequency 26-week intermittent fasting reduced homeostatic model assessment of insulin resistance (HOMA-IR) without significant weight loss. During fasting, human growth hormone (HGH) increases substantially, but whether basal HGH modifies the effect of fasting on outcomes of repeated fasting is unknown. In a post hoc analysis of a randomized controlled trial (registration: clinicaltrials.gov, NCT02770313, May 12, 2016), subjects (N = 68) were adults ages 21–70 years with modest cholesterol elevation, ≥1 metabolic syndrome component, available HGH measurements, no chronic disease, and no statin or anti-diabetes medication. Randomization was 1:1 to intermittent fasting (24-hour, water-only, twice-per-week for 4 weeks, then once-per-week for 22 weeks) or 26-week ad libitum control. General linear modeling evaluated the interaction of trial arm with baseline HGH for HOMA-IR changes. Subjects with lower baseline HGH had 26-week HOMA-IR changes (p = 0.003) of −1.04 ± 0.99 for fasting versus 0.60 ± 1.04 for controls. Subjects with higher baseline HGH had HOMA-IR changes (p = 0.26) of −0.69 ± 0.75 (fasting) and −0.42 ± 0.92 (controls). The interaction of fasting with lower baseline HGH was significant (p-interaction=0.004). Results were similar for insulin and glucose. Weight loss at 26 weeks was not significantly different between fasting and controls (−1.74 ± 4.81 kg vs. 0.21 ± 3.50 kg, p = 0.08) and was not correlated with changes in HOMA-IR, insulin, glucose, and HGH. In conclusion, lower baseline HGH modified the effect of low-frequency water-only 24-hour fasting in profoundly reducing HOMA-IR over 26 weeks compared both to controls and to fasting subjects with higher baseline HGH.","PeriodicalId":501710,"journal":{"name":"npj Metabolic Health and Disease","volume":" ","pages":"1-9"},"PeriodicalIF":0.0,"publicationDate":"2024-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s44324-024-00025-2.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142368741","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-23DOI: 10.1038/s44324-024-00028-z
Boyao Zhang, Thierry Schmidlin
Traditional risk factors and biomarkers of cardiovascular diseases (CVD) have been mainly discovered through clinical observations. Nevertheless, there is still a gap in knowledge in more sophisticated CVD risk factor stratification and more reliable treatment outcome prediction, highlighting the need for a more comprehensive understanding of disease mechanisms at the molecular level. This need has been addressed by integrating information derived from multiomics studies, which provides systematic insights into the different layers of the central dogma in molecular biology. With the advancement of technologies such as NMR and UPLC-MS, metabolomics have become a powerhouse in pharmaceutical and clinical research for high-throughput, robust, quantitative characterisation of metabolic profiles in various types of biospecimens. In this review, we highlight the versatile value of metabolomics spanning from targeted and untargeted identification of novel biomarkers and biochemical pathways, to tracing drug pharmacokinetics and drug-drug interactions for more personalised medication in CVD research (Fig. 1).
{"title":"Recent advances in cardiovascular disease research driven by metabolomics technologies in the context of systems biology","authors":"Boyao Zhang, Thierry Schmidlin","doi":"10.1038/s44324-024-00028-z","DOIUrl":"10.1038/s44324-024-00028-z","url":null,"abstract":"Traditional risk factors and biomarkers of cardiovascular diseases (CVD) have been mainly discovered through clinical observations. Nevertheless, there is still a gap in knowledge in more sophisticated CVD risk factor stratification and more reliable treatment outcome prediction, highlighting the need for a more comprehensive understanding of disease mechanisms at the molecular level. This need has been addressed by integrating information derived from multiomics studies, which provides systematic insights into the different layers of the central dogma in molecular biology. With the advancement of technologies such as NMR and UPLC-MS, metabolomics have become a powerhouse in pharmaceutical and clinical research for high-throughput, robust, quantitative characterisation of metabolic profiles in various types of biospecimens. In this review, we highlight the versatile value of metabolomics spanning from targeted and untargeted identification of novel biomarkers and biochemical pathways, to tracing drug pharmacokinetics and drug-drug interactions for more personalised medication in CVD research (Fig. 1).","PeriodicalId":501710,"journal":{"name":"npj Metabolic Health and Disease","volume":" ","pages":"1-12"},"PeriodicalIF":0.0,"publicationDate":"2024-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s44324-024-00028-z.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142276665","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-02DOI: 10.1038/s44324-024-00017-2
Nia G. Hammond, Robert B. Cameron, Brandon Faubert
Advances in cancer biology have highlighted metabolic reprogramming as an essential aspect of tumorigenesis and progression. However, recent efforts to study tumor metabolism in vivo have identified some disconnects between in vitro and in vivo biology. This is due, at least in part, to the simplified nature of cell culture models and highlights a growing need to utilize more physiologically relevant approaches to more accurately assess tumor metabolism. In this review, we outline the evolution of our understanding of cancer metabolism and discuss some discrepancies between in vitro and in vivo conditions. We describe how the development of physiological media, in combination with advanced culturing methods, can bridge the gap between in vitro and in vivo metabolism.
{"title":"Beyond glucose and Warburg: finding the sweet spot in cancer metabolism models","authors":"Nia G. Hammond, Robert B. Cameron, Brandon Faubert","doi":"10.1038/s44324-024-00017-2","DOIUrl":"10.1038/s44324-024-00017-2","url":null,"abstract":"Advances in cancer biology have highlighted metabolic reprogramming as an essential aspect of tumorigenesis and progression. However, recent efforts to study tumor metabolism in vivo have identified some disconnects between in vitro and in vivo biology. This is due, at least in part, to the simplified nature of cell culture models and highlights a growing need to utilize more physiologically relevant approaches to more accurately assess tumor metabolism. In this review, we outline the evolution of our understanding of cancer metabolism and discuss some discrepancies between in vitro and in vivo conditions. We describe how the development of physiological media, in combination with advanced culturing methods, can bridge the gap between in vitro and in vivo metabolism.","PeriodicalId":501710,"journal":{"name":"npj Metabolic Health and Disease","volume":" ","pages":"1-7"},"PeriodicalIF":0.0,"publicationDate":"2024-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s44324-024-00017-2.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142117964","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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