npj Metabolic Health and Disease最新文献_第2页

Publisher Correction: Valproic acid targets IDH1 mutants through alteration of lipid metabolism 出版商更正：丙戊酸通过改变脂质代谢靶向IDH1突变体

npj Metabolic Health and Disease Pub Date : 2024-10-18 DOI: 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

引用次数: 0

Ketone body metabolism and cardiometabolic implications for cognitive health 酮体代谢和心脏代谢对认知健康的影响

npj Metabolic Health and Disease Pub Date : 2024-10-11 DOI: 10.1038/s44324-024-00029-y

Kyle Fulghum, Sebastian F. Salathe, Xin Davis, John P. Thyfault, Patrycja Puchalska, Peter A. Crawford

{"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}

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Hypothalamic neuronal-glial crosstalk in metabolic disease 代谢性疾病中的下丘脑神经元-神经胶质串扰

npj Metabolic Health and Disease Pub Date : 2024-10-04 DOI: 10.1038/s44324-024-00026-1

Linda T. Nguyen, Garron T. Dodd

{"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}

引用次数: 0

Putting metabolism centre stage in health and disease 将新陈代谢置于健康和疾病的中心位置

npj Metabolic Health and Disease Pub Date : 2024-10-04 DOI: 10.1038/s44324-024-00032-3

M. K. Montgomery

引用次数: 0

Insulin resistance reduction, intermittent fasting, and human growth hormone: secondary analysis of a randomized trial 减少胰岛素抵抗、间歇性禁食和人体生长激素：随机试验的二次分析

npj Metabolic Health and Disease Pub Date : 2024-10-03 DOI: 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

{"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}

引用次数: 0

Recent advances in cardiovascular disease research driven by metabolomics technologies in the context of systems biology 系统生物学背景下代谢组学技术推动心血管疾病研究的最新进展

npj Metabolic Health and Disease Pub Date : 2024-09-23 DOI: 10.1038/s44324-024-00028-z

Boyao Zhang, Thierry Schmidlin

{"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}

引用次数: 0

Beyond glucose and Warburg: finding the sweet spot in cancer metabolism models 超越葡萄糖和沃伯格：寻找癌症代谢模型的甜蜜点

npj Metabolic Health and Disease Pub Date : 2024-09-02 DOI: 10.1038/s44324-024-00017-2

Nia G. Hammond, Robert B. Cameron, Brandon Faubert

引用次数: 0

Author Correction: Thyroid hormone receptor beta (THRB) dependent regulation of diurnal hepatic lipid metabolism in adult male mice 作者更正：成年雄性小鼠甲状腺激素受体β（THRB）对昼夜肝脂代谢的依赖性调节

npj Metabolic Health and Disease Pub Date : 2024-09-02 DOI: 10.1038/s44324-024-00031-4

Leonardo Vinicius Monteiro de Assis, Lisbeth Harder, Julica Inderhees, Olaf Jöhren, Jens Mittag, Henrik Oster

引用次数: 0

Lipidomics and metabolomics as potential biomarkers for breast cancer progression 脂质组学和代谢组学作为乳腺癌进展的潜在生物标记物

npj Metabolic Health and Disease Pub Date : 2024-09-02 DOI: 10.1038/s44324-024-00027-0

Alanis Carmona, Samir Mitri, Ted A. James, Jessalyn M. Ubellacker

{"title":"Lipidomics and metabolomics as potential biomarkers for breast cancer progression","authors":"Alanis Carmona, Samir Mitri, Ted A. James, Jessalyn M. Ubellacker","doi":"10.1038/s44324-024-00027-0","DOIUrl":"10.1038/s44324-024-00027-0","url":null,"abstract":"Breast cancer is the most prevalent cancer among women in the United States, representing ~30% of all new female cancer cases annually. For the year 2024, it is estimated that 310,720 new instances of invasive breast cancer will be diagnosed, and breast cancer will be responsible for over 42,000 deaths among women. Today, despite the availability of numerous treatments for breast cancer and its symptoms, most cancer-related deaths result from metastasis for which there is no treatment. This emphasizes the importance of early detection and treatment of breast cancer before it spreads. For initial detection and staging of breast cancer, clinicians routinely employ mammography and ultrasonography, which, while effective for broad screening, have limitations in sensitivity and specificity. Advanced biomarkers could significantly enhance the precision of early detection, enable more accurate monitoring of disease evolution, and facilitate the development of personalized treatment plans tailored to the specific molecular profile of each tumor. This would not only improve therapeutic outcomes, but also help in avoiding overtreatment and the associated side effects, thereby improving the quality of life for patients. Thus, the pursuit of novel biomarkers, potentially encompassing metabolomic and lipidomic signatures, is essential for advancing breast cancer diagnosis and treatment. In this brief review, we will provide an overview of the current translational potential of metabolic and lipidomic biomarkers for predicting breast cancer prognosis and response to therapy.","PeriodicalId":501710,"journal":{"name":"npj Metabolic Health and Disease","volume":" ","pages":"1-9"},"PeriodicalIF":0.0,"publicationDate":"2024-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s44324-024-00027-0.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142117963","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}

引用次数: 0

Valproic acid targets IDH1 mutants through alteration of lipid metabolism 丙戊酸通过改变脂质代谢靶向 IDH1 突变体

npj Metabolic Health and Disease Pub Date : 2024-08-13 DOI: 10.1038/s44324-024-00021-6

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":"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/s44324-024-00021-6","DOIUrl":"10.1038/s44324-024-00021-6","url":null,"abstract":"Histone deacetylases (HDACs) have a wide range of targets and can rewire both the chromatin and lipidome of cancer cells. In this study, we show that valproic acid (VPA), a brain penetrant anti-seizure medication and histone deacetylase inhibitor, inhibits the growth of IDH1 mutant tumors in vivo and in vitro, with at least some selectivity over IDH1 wild-type tumors. Surprisingly, genes upregulated by VPA showed no enhanced chromatin accessibility at the promoter, but there was a correlation between VPA-downregulated genes and diminished promoter chromatin accessibility. VPA inhibited the transcription of lipogenic genes and these lipogenic genes showed significant decreases in promoter chromatin accessibility only in the IDH1 MT glioma cell lines tested. VPA inhibited the mTOR pathway and a key lipogenic gene, fatty acid synthase (FASN). Both VPA and a selective FASN inhibitor TVB-2640 rewired the lipidome and promoted apoptosis in an IDH1 MT but not in an IDH1 WT glioma cell line. We further find that HDACs are involved in the regulation of lipogenic genes and HDAC6 is particularly important for the regulation of FASN in IDH1 MT glioma. Finally, we show that FASN knockdown alone and VPA in combination with FASN knockdown significantly improved the survival of mice in an IDH1 MT primary orthotopic xenograft model in vivo. We conclude that targeting fatty acid metabolism through HDAC inhibition and/or FASN inhibition may be a novel therapeutic opportunity in IDH1 mutant gliomas.","PeriodicalId":501710,"journal":{"name":"npj Metabolic Health and Disease","volume":" ","pages":"1-14"},"PeriodicalIF":0.0,"publicationDate":"2024-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s44324-024-00021-6.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141973744","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}

引用次数: 0