Nature metabolism最新文献_第6页

IF 20.8 1区医学

Nature metabolism Pub Date : 2025-07-23 DOI: 10.1038/s42255-025-01327-5

Jan-Bernd Funcke, Philipp E. Scherer

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N-acetylaspartate from fat cells regulates postprandial body temperature 来自脂肪细胞的n -乙酰天冬氨酸调节餐后体温

IF 20.8 1区医学

Nature metabolism Pub Date : 2025-07-23 DOI: 10.1038/s42255-025-01334-6

Jessica B. Felix, Pradip K. Saha, Evelyn L. de Groot, Lin Tan, Robert Sharp, Elizabeth S. Anaya, Yafang Li, Holly Quang, Nooshin Saidi, Layla Abushamat, Christie M. Ballantyne, Christopher I. Amos, Philip L. Lorenzi, Samuel Klein, Xia Gao, Sean M. Hartig

{"title":"N-acetylaspartate from fat cells regulates postprandial body temperature","authors":"Jessica B. Felix, Pradip K. Saha, Evelyn L. de Groot, Lin Tan, Robert Sharp, Elizabeth S. Anaya, Yafang Li, Holly Quang, Nooshin Saidi, Layla Abushamat, Christie M. Ballantyne, Christopher I. Amos, Philip L. Lorenzi, Samuel Klein, Xia Gao, Sean M. Hartig","doi":"10.1038/s42255-025-01334-6","DOIUrl":"10.1038/s42255-025-01334-6","url":null,"abstract":"N-acetylaspartate (NAA), the brain’s second most abundant metabolite, provides essential substrates for myelination through its hydrolysis1. However, the physiological roles of NAA in other tissues remain unknown. Here, we show that aspartoacylase (ASPA) expression in white adipose tissue (WAT) governs blood NAA levels for postprandial body temperature regulation. Genetic ablation of Aspa in mice resulted in systemically elevated NAA levels, and the ensuing accumulation in WAT stimulated pyrimidine production. Stable isotope tracing confirmed higher incorporation of glucose-derived carbon into pyrimidine metabolites in Aspa knockout cells. Additionally, serum NAA levels positively correlated with the abundance of the pyrimidine intermediate orotidine 5′-monophosphate, and this relationship predicted lower body mass index in humans. Using whole-body and tissue-specific knockout mouse models, we observed that fat cells provided plasma NAA and suppressed postprandial body temperature elevation. Moreover, unopposed NAA from adipocytes greatly enhanced whole-body glucose disposal exclusively in WAT. Exogenous NAA also increased plasma pyrimidines and lowered body temperature. These data place WAT-derived NAA as an endocrine regulator of postprandial body temperature and define broader roles for metabolic homeostasis. Aspartoacylase expression in white adipose tissue regulates circulating levels of N-acetylaspartate, which in turn modulates plasma pyrimidine levels and regulates postprandial body temperature.","PeriodicalId":19038,"journal":{"name":"Nature metabolism","volume":"7 8","pages":"1524-1535"},"PeriodicalIF":20.8,"publicationDate":"2025-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.comhttps://www.nature.com/articles/s42255-025-01334-6.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144684800","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

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LONP1 loss causes mitochondrial mayhem in β-cells LONP1缺失导致β细胞线粒体混乱

IF 20.8 1区医学

Nature metabolism Pub Date : 2025-07-21 DOI: 10.1038/s42255-025-01328-4

Kok Lim Kua, Carmella Evans-Molina

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LONP1 regulation of mitochondrial protein folding provides insight into beta cell failure in type 2 diabetes LONP1对线粒体蛋白折叠的调控为2型糖尿病的β细胞衰竭提供了新的视角

IF 20.8 1区医学

Nature metabolism Pub Date : 2025-07-21 DOI: 10.1038/s42255-025-01333-7

Jin Li, Yamei Deng, Marie Gasser, Jie Zhu, Emily M. Walker, Vaibhav Sidarala, Emma C. Reck, Dre L. Hubers, Mabelle B. Pasmooij, Chun-Shik Shin, Khushdeep Bandesh, Eftyhmios Motakis, Siddhi Nargund, Romy Kursawe, Venkatesha Basrur, Alexey I. Nesvizhskii, Michael L. Stitzel, David C. Chan, Guy A. Rutter, Scott A. Soleimanpour

{"title":"LONP1 regulation of mitochondrial protein folding provides insight into beta cell failure in type 2 diabetes","authors":"Jin Li, Yamei Deng, Marie Gasser, Jie Zhu, Emily M. Walker, Vaibhav Sidarala, Emma C. Reck, Dre L. Hubers, Mabelle B. Pasmooij, Chun-Shik Shin, Khushdeep Bandesh, Eftyhmios Motakis, Siddhi Nargund, Romy Kursawe, Venkatesha Basrur, Alexey I. Nesvizhskii, Michael L. Stitzel, David C. Chan, Guy A. Rutter, Scott A. Soleimanpour","doi":"10.1038/s42255-025-01333-7","DOIUrl":"10.1038/s42255-025-01333-7","url":null,"abstract":"Protein misfolding is a contributor to the development of type 2 diabetes (T2D), but the specific role of impaired proteostasis is unclear. Here we show a robust accumulation of misfolded proteins in the mitochondria of human pancreatic islets from patients with T2D and elucidate its impact on β cell viability through the mitochondrial matrix protease LONP1. Quantitative proteomics studies of protein aggregates reveal that islets from donors with T2D have a signature resembling mitochondrial rather than endoplasmic reticulum protein misfolding. Loss of LONP1, a vital component of the mitochondrial proteostatic machinery, with reduced expression in the β cells of donors with T2D, yields mitochondrial protein misfolding and reduced respiratory function, leading to β cell apoptosis and hyperglycaemia. LONP1 gain of function ameliorates mitochondrial protein misfolding and restores human β cell survival after glucolipotoxicity via a protease-independent effect requiring LONP1-mitochondrial HSP70 chaperone activity. Thus, LONP1 promotes β cell survival and prevents hyperglycaemia by facilitating mitochondrial protein folding. These observations provide insights into the nature of proteotoxicity that promotes β cell loss during the pathogenesis of T2D, which could be considered as future therapeutic targets. LONP1, whose expression is downregulated in islets from donors with type 2 diabetes, is vital to mediate efficient mitochondrial protein folding, thus preventing proteotoxicity and promoting islet β cell survival and function.","PeriodicalId":19038,"journal":{"name":"Nature metabolism","volume":"7 8","pages":"1570-1592"},"PeriodicalIF":20.8,"publicationDate":"2025-07-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.comhttps://www.nature.com/articles/s42255-025-01333-7.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144669741","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

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Mitochondrial age-classes expand the heterogeneity of tissue-resident stem cells 线粒体年龄等级扩大了组织驻留干细胞的异质性

IF 20.8 1区医学

Nature metabolism Pub Date : 2025-07-14 DOI: 10.1038/s42255-025-01326-6

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Old mitochondria regulate niche renewal via α-ketoglutarate metabolism in stem cells 干细胞中衰老线粒体通过α-酮戊二酸代谢调节生态位更新

IF 20.8 1区医学

Nature metabolism Pub Date : 2025-07-14 DOI: 10.1038/s42255-025-01325-7

Simon Andersson, Hien Bui, Arto Viitanen, Daniel Borshagovski, Ella Salminen, Sami Kilpinen, Angelika Gebhart, Emilia Kuuluvainen, Swetha Gopalakrishnan, Nina Peltokangas, Martyn James, Kaia Achim, Eija Jokitalo, Petri Auvinen, Ville Hietakangas, Pekka Katajisto

{"title":"Old mitochondria regulate niche renewal via α-ketoglutarate metabolism in stem cells","authors":"Simon Andersson, Hien Bui, Arto Viitanen, Daniel Borshagovski, Ella Salminen, Sami Kilpinen, Angelika Gebhart, Emilia Kuuluvainen, Swetha Gopalakrishnan, Nina Peltokangas, Martyn James, Kaia Achim, Eija Jokitalo, Petri Auvinen, Ville Hietakangas, Pekka Katajisto","doi":"10.1038/s42255-025-01325-7","DOIUrl":"10.1038/s42255-025-01325-7","url":null,"abstract":"Cellular metabolism is a key regulator of cell fate1, raising the possibility that the recently discovered metabolic heterogeneity between newly synthesized and chronologically old organelles may affect stem cell fate in tissues2,3. In the small intestine, intestinal stem cells (ISCs)4 produce metabolically distinct progeny5, including their Paneth cell (PC) niche6. Here we show that asymmetric cell division of mouse ISCs generates a subset enriched for old mitochondria (ISCmito-O), which are metabolically distinct, and form organoids independently of niche because of their ability to recreate the PC niche. ISCmito-O mitochondria produce more α-ketoglutarate, driving ten-eleven translocation-mediated epigenetic changes that promote PC formation. In vivo α-ketoglutarate supplementation enhanced PC turnover and niche renewal, aiding recovery from chemotherapy-induced damage in aged mice. Our results reveal a subpopulation of ISCs whose old mitochondria metabolically regulate cell fate, and provide proof of principle for metabolically promoted replacement of specific aged cell types in vivo. Andersson et al. show that intestinal stem cells enriched for old mitochondria are metabolically distinct and have enhanced ability to regenerate the epithelial niche.","PeriodicalId":19038,"journal":{"name":"Nature metabolism","volume":"7 7","pages":"1344-1357"},"PeriodicalIF":20.8,"publicationDate":"2025-07-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.comhttps://www.nature.com/articles/s42255-025-01325-7.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144622476","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

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Shaping the future of cardiometabolic innovation: advances and opportunities 塑造心脏代谢创新的未来：进步与机遇

IF 20.8 1区医学

Nature metabolism Pub Date : 2025-07-11 DOI: 10.1038/s42255-025-01343-5

Christoffer Clemmensen, Zachary Gerhart-Hines, Thue W. Schwartz, Juleen R. Zierath, Kei Sakamoto

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CagriSema drives weight loss in rats by reducing energy intake and preserving energy expenditure CagriSema通过减少能量摄入和保持能量消耗来促进大鼠体重减轻

IF 20.8 1区医学

Nature metabolism Pub Date : 2025-07-08 DOI: 10.1038/s42255-025-01324-8

Julie Mie Jacobsen, Jens Frey Halling, Ida Blom, Jaime Moreno Martinez, Bjørn Hald, Kent Pedersen, Johannes Josef Fels, Søren Snitker, Anna Secher, Sofia Lundh, Carel W. le Roux, Kirsten Raun, Marc L. Reitman, Rune Ehrenreich Kuhre

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Multi-omic analysis reveals transkingdom gut dysbiosis in metabolic dysfunction-associated steatotic liver disease 多组学分析揭示代谢功能障碍相关脂肪变性肝病的跨王国肠道生态失调

IF 20.8 1区医学

Nature metabolism Pub Date : 2025-07-02 DOI: 10.1038/s42255-025-01318-6

Hanseul Kim, Paul Nelson, Etienne Nzabarushimana, Jiaxian Shen, Jordan Jensen, Amrisha Bhosle, Chengchen Li, Nawon Lee, Christine Everett, Brittany Berdy, Giana Frongillo, Jonathan Livny, Frank B. Hu, Tracey G. Simon, Lauren McIver, Eric A. Franzosa, Andrew T. Chan, Boris Hayete, Kelsey N. Thompson, Curtis Huttenhower, Long H. Nguyen

{"title":"Multi-omic analysis reveals transkingdom gut dysbiosis in metabolic dysfunction-associated steatotic liver disease","authors":"Hanseul Kim, Paul Nelson, Etienne Nzabarushimana, Jiaxian Shen, Jordan Jensen, Amrisha Bhosle, Chengchen Li, Nawon Lee, Christine Everett, Brittany Berdy, Giana Frongillo, Jonathan Livny, Frank B. Hu, Tracey G. Simon, Lauren McIver, Eric A. Franzosa, Andrew T. Chan, Boris Hayete, Kelsey N. Thompson, Curtis Huttenhower, Long H. Nguyen","doi":"10.1038/s42255-025-01318-6","DOIUrl":"10.1038/s42255-025-01318-6","url":null,"abstract":"Metabolic dysfunction-associated steatotic liver disease (MASLD) is a common condition linked to obesity and the metabolic syndrome, yet its transkingdom connections have been under-investigated. We performed high-resolution multi-omic profiling—including stool metagenomes, metatranscriptomes and metabolomes—in 211 MASLD cases and 502 controls from a cohort of female nurses. Here we show that MASLD is associated with shifts in 66 gut bacterial species, including widespread enrichment of oral-typical microbes, and transkingdom dysbiosis involving not only bacterial but also viral taxa. Streptococcus spp. are more abundant in non-lean versus lean MASLD, the latter being a paradoxical subtype of a disease typically associated with increased adiposity. These microbial changes correspond with shifts in transcripts and metabolites, including increases in polyamines and acylcarnitines and reductions in secondary bile acids. We highlight gut viral perturbations in MASLD, showing that expansions of bacteriophage targeting oral-typical bacteria correspond to expansions of their bacterial hosts in the gut. We provide a comprehensive resource for understanding MASLD and highlight transkingdom multi-omic microbial shifts as potential contributors to its aetiopathogenesis. High-resolution multi-omic profiling indicates widespread gut dysbiosis in individuals with MASLD, also affecting the virome, and reveals microbial signatures that can classify MASLD and its subtypes.","PeriodicalId":19038,"journal":{"name":"Nature metabolism","volume":"7 7","pages":"1476-1492"},"PeriodicalIF":20.8,"publicationDate":"2025-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144534051","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}

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Retraction Note: Brown adipose tissue-derived Nrg4 alleviates endothelial inflammation and atherosclerosis in male mice 注：棕色脂肪组织来源的Nrg4可减轻雄性小鼠内皮炎症和动脉粥样硬化。

IF 20.8 1区医学

Nature metabolism Pub Date : 2025-07-02 DOI: 10.1038/s42255-025-01344-4

Lingfeng Shi, Yixiang Li, Xiaoli Xu, Yangyang Cheng, Biying Meng, Jinling Xu, Lin Xiang, Jiajia Zhang, Kaiyue He, Jiayue Tong, Junxia Zhang, Lingwei Xiang, Guangda Xiang

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