Nature metabolism最新文献

Cryptic phosphoribosylase activity of NAMPT restricts the virion incorporation of viral proteins NAMPT 的隐性磷酸核糖酶活性限制了病毒蛋白在病毒中的结合

IF 20.8 1区医学

Nature metabolism Pub Date : 2024-11-21 DOI: 10.1038/s42255-024-01162-0

Shu Feng, Na Xie, Yongzhen Liu, Chao Qin, Ali Can Savas, Ting-Yu Wang, Shutong Li, Youliang Rao, Alexandra Shambayate, Tsui-Fen Chou, Charles Brenner, Canhua Huang, Pinghui Feng

{"title":"Cryptic phosphoribosylase activity of NAMPT restricts the virion incorporation of viral proteins","authors":"Shu Feng, Na Xie, Yongzhen Liu, Chao Qin, Ali Can Savas, Ting-Yu Wang, Shutong Li, Youliang Rao, Alexandra Shambayate, Tsui-Fen Chou, Charles Brenner, Canhua Huang, Pinghui Feng","doi":"10.1038/s42255-024-01162-0","DOIUrl":"https://doi.org/10.1038/s42255-024-01162-0","url":null,"abstract":"As obligate intracellular pathogens, viruses activate host metabolic enzymes to supply intermediates that support progeny production. Nicotinamide phosphoribosyltransferase (NAMPT), the rate-limiting enzyme of salvage nicotinamide adenine dinucleotide (NAD+) synthesis, is an interferon-inducible protein that inhibits the replication of several RNA and DNA viruses through unknown mechanisms. Here, we show that NAMPT restricts herpes simplex virus type 1 (HSV-1) replication by impeding the virion incorporation of viral proteins owing to its phosphoribosyl-hydrolase (phosphoribosylase) activity, which is independent of the role of NAMPT in NAD+ synthesis. Proteomics analysis of HSV-1-infected cells identifies phosphoribosylated viral structural proteins, particularly glycoproteins and tegument proteins, which are de-phosphoribosylated by NAMPT in vitro and in cells. Chimeric and recombinant HSV-1 carrying phosphoribosylation-resistant mutations show that phosphoribosylation promotes the incorporation of structural proteins into HSV-1 virions and subsequent virus entry. Loss of NAMPT renders mice highly susceptible to HSV-1 infection. Our work describes an additional enzymatic activity of a metabolic enzyme in viral infection and host defence, offering a system to interrogate the roles of protein phosphoribosylation in metazoans.","PeriodicalId":19038,"journal":{"name":"Nature metabolism","volume":"191 1","pages":""},"PeriodicalIF":20.8,"publicationDate":"2024-11-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142678635","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Microviridae bacteriophages in the gut microbiome and food addiction in humans 人类肠道微生物群中的微病毒科噬菌体与食物成瘾

IF 20.8 1区医学

Nature metabolism Pub Date : 2024-11-20 DOI: 10.1038/s42255-024-01158-w

引用次数: 0

Human PERIOD3 variants lead to winter depression-like behaviours via glucocorticoid signalling 人类 PERIOD3 变体通过糖皮质激素信号导致类似冬季抑郁症的行为

IF 20.8 1区医学

Nature metabolism Pub Date : 2024-11-11 DOI: 10.1038/s42255-024-01163-z

Qian Gao, Zhiwei Tang, Haili Wang, Maya Yamazaki, Jia Jiang, Ying-Hui Fu, Louis J. Ptacek, Luoying Zhang

{"title":"Human PERIOD3 variants lead to winter depression-like behaviours via glucocorticoid signalling","authors":"Qian Gao, Zhiwei Tang, Haili Wang, Maya Yamazaki, Jia Jiang, Ying-Hui Fu, Louis J. Ptacek, Luoying Zhang","doi":"10.1038/s42255-024-01163-z","DOIUrl":"https://doi.org/10.1038/s42255-024-01163-z","url":null,"abstract":"Our brain adapts to seasonal changes. Mis-adaptations may lead to seasonal patterns in several psychiatric disorders, but we know little regarding the underlying mechanisms. Our previous work identified two variants in the human circadian clock gene PERIOD3 (PER3), that is, P415A and H417R, which are associated with winter depression, but whether and how these variants lead to the disorder remain to be characterized. Here we find that male mice carrying human P415A and H417R display winter depression-like behaviours that are caused by the actions of P415A and H417R in the adrenal gland. Systemic corticosterone level is downregulated in adaptation to shortening of day length, while P415A and H417R eliminate this downregulation by increasing corticosterone synthesis. Enhanced glucocorticoid signalling represses the transcription of Tph2, which encodes the rate-limiting enzyme of serotonin synthesis, leading to increased depression-like behaviours. Taken together, our findings unveil a mechanism according to which human variants contribute to seasonal mood traits.","PeriodicalId":19038,"journal":{"name":"Nature metabolism","volume":"33 1","pages":""},"PeriodicalIF":20.8,"publicationDate":"2024-11-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142597982","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

AI-READI: rethinking AI data collection, preparation and sharing in diabetes research and beyond AI-READI：重新思考糖尿病研究及其他领域的人工智能数据收集、准备和共享问题

IF 20.8 1区医学

Nature metabolism Pub Date : 2024-11-08 DOI: 10.1038/s42255-024-01165-x

引用次数: 0

Author Correction: Branched-chain α-ketoacids aerobically activate HIF1α signalling in vascular cells. 作者更正：支链α-酮酸有氧激活血管细胞中的 HIF1α 信号。

IF 18.9 1区医学

Nature metabolism Pub Date : 2024-11-05 DOI: 10.1038/s42255-024-01171-z

Wusheng Xiao, Nishith Shrimali, Niv Vigder, William M Oldham, Clary B Clish, Huamei He, Samantha J Wong, Bradley M Wertheim, Elena Arons, Marcia C Haigis, Jane A Leopold, Joseph Loscalzo

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A pathogenic role for IL-10 signalling in capillary stalling and cognitive impairment in type 1 diabetes IL-10 信号在 1 型糖尿病毛细血管阻滞和认知障碍中的致病作用

IF 20.8 1区医学

Nature metabolism Pub Date : 2024-11-04 DOI: 10.1038/s42255-024-01159-9

Sorabh Sharma, Manjinder Cheema, Patrick L. Reeson, Kamal Narayana, Roobina Boghozian, Ana Paula Cota, Tara P. Brosschot, Rachael D. FitzPatrick, Jakob Körbelin, Lisa A. Reynolds, Craig E. Brown

{"title":"A pathogenic role for IL-10 signalling in capillary stalling and cognitive impairment in type 1 diabetes","authors":"Sorabh Sharma, Manjinder Cheema, Patrick L. Reeson, Kamal Narayana, Roobina Boghozian, Ana Paula Cota, Tara P. Brosschot, Rachael D. FitzPatrick, Jakob Körbelin, Lisa A. Reynolds, Craig E. Brown","doi":"10.1038/s42255-024-01159-9","DOIUrl":"https://doi.org/10.1038/s42255-024-01159-9","url":null,"abstract":"Vascular pathology is associated with cognitive impairment in diseases such as type 1 diabetes; however, how capillary flow is affected and the underlying mechanisms remain elusive. Here we show that capillaries in the diabetic mouse brain in both sexes are prone to stalling, with blocks consisting primarily of erythrocytes in branches off ascending venules. Screening for circulating inflammatory cytokines revealed persistently high levels of interleukin-10 (IL-10) in diabetic mice. Contrary to expectation, stimulating IL-10 signalling increased capillary obstruction, whereas inhibiting IL-10 receptors with neutralizing antibodies or endothelial specific knockdown in diabetic mice reversed these impairments. Chronic treatment of diabetic mice with IL-10 receptor neutralizing antibodies improved cerebral blood flow, increased capillary flux and diameter, downregulated haemostasis and cell adhesion-related gene expression, and reversed cognitive deficits. These data suggest that IL-10 signalling has an unexpected pathogenic role in cerebral microcirculatory defects and cognitive impairment associated with type 1 diabetes.","PeriodicalId":19038,"journal":{"name":"Nature metabolism","volume":"4 1","pages":""},"PeriodicalIF":20.8,"publicationDate":"2024-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142574461","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Diabetes, IL-10 and the brain’s microvascular crisis 糖尿病、IL-10 和大脑微血管危机

IF 20.8 1区医学

Nature metabolism Pub Date : 2024-11-04 DOI: 10.1038/s42255-024-01161-1

Celine E. Riera

引用次数: 0

Effect of acute exercise in carriers of TBC1D4 mutation 急性运动对 TBC1D4 基因突变携带者的影响

IF 20.8 1区医学

Nature metabolism Pub Date : 2024-10-31 DOI: 10.1038/s42255-024-01116-6

Leslie J. Baier, Clifton Bogardus

引用次数: 0

Skeletal muscle from TBC1D4 p.Arg684Ter variant carriers is severely insulin resistant but exhibits normal metabolic responses during exercise TBC1D4 p.Arg684Ter 变体携带者的骨骼肌具有严重的胰岛素抵抗，但在运动过程中表现出正常的代谢反应

IF 20.8 1区医学

Nature metabolism Pub Date : 2024-10-31 DOI: 10.1038/s42255-024-01153-1

Jonas M. Kristensen, Rasmus Kjøbsted, Trine J. Larsen, Christian S. Carl, Janne R. Hingst, Johan Onslev, Jesper B. Birk, Anette Thorup, Dorte E. Steenberg, Jonas R. Knudsen, Nicolai S. Henriksen, Elise J. Needham, Jens F. Halling, Anders Gudiksen, Carsten F. Rundsten, Kristian E. Hanghøj, Sara E. Stinson, Birgitte Hoier, Camilla C. Hansen, Thomas E. Jensen, Ylva Hellsten, Henriette Pilegaard, Niels Grarup, Jesper Olesen, Sean J. Humphrey, David E. James, Michael L. Pedersen, Erik A. Richter, Torben Hansen, Marit E. Jørgensen, Jørgen F. P. Wojtaszewski

{"title":"Skeletal muscle from TBC1D4 p.Arg684Ter variant carriers is severely insulin resistant but exhibits normal metabolic responses during exercise","authors":"Jonas M. Kristensen, Rasmus Kjøbsted, Trine J. Larsen, Christian S. Carl, Janne R. Hingst, Johan Onslev, Jesper B. Birk, Anette Thorup, Dorte E. Steenberg, Jonas R. Knudsen, Nicolai S. Henriksen, Elise J. Needham, Jens F. Halling, Anders Gudiksen, Carsten F. Rundsten, Kristian E. Hanghøj, Sara E. Stinson, Birgitte Hoier, Camilla C. Hansen, Thomas E. Jensen, Ylva Hellsten, Henriette Pilegaard, Niels Grarup, Jesper Olesen, Sean J. Humphrey, David E. James, Michael L. Pedersen, Erik A. Richter, Torben Hansen, Marit E. Jørgensen, Jørgen F. P. Wojtaszewski","doi":"10.1038/s42255-024-01153-1","DOIUrl":"https://doi.org/10.1038/s42255-024-01153-1","url":null,"abstract":"In the Greenlandic Inuit population, 4% are homozygous carriers of a genetic nonsense TBC1D4 p.Arg684Ter variant leading to loss of the muscle-specific isoform of TBC1D4 and an approximately tenfold increased risk of type 2 diabetes1. Here we show the metabolic consequences of this variant in four female and four male homozygous carriers and matched controls. An extended glucose tolerance test reveals prolonged hyperglycaemia followed by reactive hypoglycaemia in the carriers. Whole-body glucose disposal is impaired during euglycaemic-hyperinsulinaemic clamp conditions and associates with severe insulin resistance in skeletal muscle only. Notably, a marked reduction in muscle glucose transporter GLUT4 and associated proteins is observed. While metabolic regulation during exercise remains normal, the insulin-sensitizing effect of a single exercise bout is compromised. Thus, loss of the muscle-specific isoform of TBC1D4 causes severe skeletal muscle insulin resistance without baseline hyperinsulinaemia. However, physical activity can ameliorate this condition. These observations offer avenues for personalized interventions and targeted preventive strategies.","PeriodicalId":19038,"journal":{"name":"Nature metabolism","volume":"15 1","pages":""},"PeriodicalIF":20.8,"publicationDate":"2024-10-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142555777","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Branched-chain α-ketoacids aerobically activate HIF1α signalling in vascular cells 支链α-酮酸有氧激活血管细胞中的 HIF1α 信号传导

IF 20.8 1区医学

Nature metabolism Pub Date : 2024-10-29 DOI: 10.1038/s42255-024-01150-4

Wusheng Xiao, Nishith Shrimali, Niv Vigder, William M. Oldham, Clary B. Clish, Huamei He, Samantha J. Wong, Bradley M. Wertheim, Elena Arons, Marcia C. Haigis, Jane A. Leopold, Joseph Loscalzo

{"title":"Branched-chain α-ketoacids aerobically activate HIF1α signalling in vascular cells","authors":"Wusheng Xiao, Nishith Shrimali, Niv Vigder, William M. Oldham, Clary B. Clish, Huamei He, Samantha J. Wong, Bradley M. Wertheim, Elena Arons, Marcia C. Haigis, Jane A. Leopold, Joseph Loscalzo","doi":"10.1038/s42255-024-01150-4","DOIUrl":"https://doi.org/10.1038/s42255-024-01150-4","url":null,"abstract":"Hypoxia-inducible factor 1α (HIF1α) is a master regulator of biological processes in hypoxia. Yet, the mechanisms and biological consequences of aerobic HIF1α activation by intrinsic factors, particularly in normal (primary) cells, remain elusive. Here we show that HIF1α signalling is activated in several human primary vascular cells in normoxia and in vascular smooth muscle cells of normal human lungs. Mechanistically, aerobic HIF1α activation is mediated by paracrine secretion of three branched-chain α-ketoacids (BCKAs), which suppress PHD2 activity via direct inhibition and via LDHA-mediated generation of L-2-hydroxyglutarate. BCKA-mediated HIF1α signalling activation stimulated glycolytic activity and governed a phenotypic switch of pulmonary artery smooth muscle cells, which correlated with BCKA metabolic dysregulation and pathophenotypic changes in pulmonary arterial hypertension patients and male rat models. We thus identify BCKAs as previously unrecognized signalling metabolites that aerobically activate HIF1α and that the BCKA–HIF1α pathway modulates vascular smooth muscle cell function, an effect that may be relevant to pulmonary vascular pathobiology.","PeriodicalId":19038,"journal":{"name":"Nature metabolism","volume":"79 1","pages":""},"PeriodicalIF":20.8,"publicationDate":"2024-10-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142536716","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0