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A short-term, high-caloric diet has prolonged effects on brain insulin action in men
IF 20.8 1区 医学
Nature metabolism Pub Date : 2025-02-21 DOI: 10.1038/s42255-025-01226-9
Stephanie Kullmann, Lore Wagner, Robert Hauffe, Anne Kühnel, Leontine Sandforth, Ralf Veit, Corinna Dannecker, Jürgen Machann, Andreas Fritsche, Nobert Stefan, Hubert Preissl, Nils B. Kroemer, Martin Heni, André Kleinridders, Andreas L. Birkenfeld
{"title":"A short-term, high-caloric diet has prolonged effects on brain insulin action in men","authors":"Stephanie Kullmann, Lore Wagner, Robert Hauffe, Anne Kühnel, Leontine Sandforth, Ralf Veit, Corinna Dannecker, Jürgen Machann, Andreas Fritsche, Nobert Stefan, Hubert Preissl, Nils B. Kroemer, Martin Heni, André Kleinridders, Andreas L. Birkenfeld","doi":"10.1038/s42255-025-01226-9","DOIUrl":"https://doi.org/10.1038/s42255-025-01226-9","url":null,"abstract":"<p>Brain insulin responsiveness is linked to long-term weight gain and unhealthy body fat distribution. Here we show that short-term overeating with calorie-rich sweet and fatty foods triggers liver fat accumulation and disrupted brain insulin action that outlasted the time-frame of its consumption in healthy weight men. Hence, brain response to insulin can adapt to short-term changes in diet before weight gain and may facilitate the development of obesity and associated diseases.</p>","PeriodicalId":19038,"journal":{"name":"Nature metabolism","volume":"19 1","pages":""},"PeriodicalIF":20.8,"publicationDate":"2025-02-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143462435","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
Pro-inflammatory macrophages produce mitochondria-derived superoxide by reverse electron transport at complex I that regulates IL-1β release during NLRP3 inflammasome activation
IF 20.8 1区 医学
Nature metabolism Pub Date : 2025-02-19 DOI: 10.1038/s42255-025-01224-x
Alva M. Casey, Dylan G. Ryan, Hiran A. Prag, Suvagata Roy Chowdhury, Eloïse Marques, Keira Turner, Anja V. Gruszczyk, Ming Yang, Dane M. Wolf, Jan Lj. Miljkovic, Joyce Valadares, Patrick F. Chinnery, Richard C. Hartley, Christian Frezza, Julien Prudent, Michael P. Murphy
{"title":"Pro-inflammatory macrophages produce mitochondria-derived superoxide by reverse electron transport at complex I that regulates IL-1β release during NLRP3 inflammasome activation","authors":"Alva M. Casey, Dylan G. Ryan, Hiran A. Prag, Suvagata Roy Chowdhury, Eloïse Marques, Keira Turner, Anja V. Gruszczyk, Ming Yang, Dane M. Wolf, Jan Lj. Miljkovic, Joyce Valadares, Patrick F. Chinnery, Richard C. Hartley, Christian Frezza, Julien Prudent, Michael P. Murphy","doi":"10.1038/s42255-025-01224-x","DOIUrl":"https://doi.org/10.1038/s42255-025-01224-x","url":null,"abstract":"<p>Macrophages stimulated by lipopolysaccharide (LPS) generate mitochondria-derived reactive oxygen species (mtROS) that act as antimicrobial agents and redox signals; however, the mechanism of LPS-induced mitochondrial superoxide generation is unknown. Here we show that LPS-stimulated bone-marrow-derived macrophages produce superoxide by reverse electron transport (RET) at complex I of the electron transport chain. Using chemical biology and genetic approaches, we demonstrate that superoxide production is driven by LPS-induced metabolic reprogramming, which increases the proton motive force (∆p), primarily as elevated mitochondrial membrane potential (Δψ<sub>m</sub>) and maintains a reduced CoQ pool. The key metabolic changes are repurposing of ATP production from oxidative phosphorylation to glycolysis, which reduces reliance on F<sub>1</sub>F<sub>O</sub>-ATP synthase activity resulting in a higher ∆p, while oxidation of succinate sustains a reduced CoQ pool. Furthermore, the production of mtROS by RET regulates IL-1β release during NLRP3 inflammasome activation. Thus, we demonstrate that ROS generated by RET is an important mitochondria-derived signal that regulates macrophage cytokine production.</p>","PeriodicalId":19038,"journal":{"name":"Nature metabolism","volume":"12 1","pages":""},"PeriodicalIF":20.8,"publicationDate":"2025-02-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143443304","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
Querying stool for dietary information
IF 20.8 1区 医学
Nature metabolism Pub Date : 2025-02-18 DOI: 10.1038/s42255-025-01219-8
Lars O. Dragsted, Henrik M. Roager, Catalina Cuparencu
{"title":"Querying stool for dietary information","authors":"Lars O. Dragsted, Henrik M. Roager, Catalina Cuparencu","doi":"10.1038/s42255-025-01219-8","DOIUrl":"https://doi.org/10.1038/s42255-025-01219-8","url":null,"abstract":"Accurately determining food intake remains a substantial challenge in nutrition research. This issue of Nature Metabolism introduces a methodology for assessing dietary intake, using stool metagenomic data to detect food DNA from a broad range of foods.","PeriodicalId":19038,"journal":{"name":"Nature metabolism","volume":"4 1","pages":""},"PeriodicalIF":20.8,"publicationDate":"2025-02-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143435145","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
Metagenomic estimation of dietary intake from human stool
IF 20.8 1区 医学
Nature metabolism Pub Date : 2025-02-18 DOI: 10.1038/s42255-025-01220-1
Christian Diener, Hannah D. Holscher, Klara Filek, Karen D. Corbin, Christine Moissl-Eichinger, Sean M. Gibbons
{"title":"Metagenomic estimation of dietary intake from human stool","authors":"Christian Diener, Hannah D. Holscher, Klara Filek, Karen D. Corbin, Christine Moissl-Eichinger, Sean M. Gibbons","doi":"10.1038/s42255-025-01220-1","DOIUrl":"https://doi.org/10.1038/s42255-025-01220-1","url":null,"abstract":"<p>Dietary intake is tightly coupled to gut microbiota composition, human metabolism and the incidence of virtually all major chronic diseases. Dietary and nutrient intake are usually assessed using self-reporting methods, including dietary questionnaires and food records, which suffer from reporting biases and require strong compliance from study participants. Here, we present Metagenomic Estimation of Dietary Intake (MEDI): a method for quantifying food-derived DNA in human faecal metagenomes. We show that DNA-containing food components can be reliably detected in stool-derived metagenomic data, even when present at low abundances (more than ten reads). We show how MEDI dietary intake profiles can be converted into detailed metabolic representations of nutrient intake. MEDI identifies the onset of solid food consumption in infants, shows significant agreement with food frequency questionnaire responses in an adult population and shows agreement with food and nutrient intake in two controlled-feeding studies. Finally, we identify specific dietary features associated with metabolic syndrome in a large clinical cohort without dietary records, providing a proof-of-concept for detailed tracking of individual-specific, health-relevant dietary patterns without the need for questionnaires.</p>","PeriodicalId":19038,"journal":{"name":"Nature metabolism","volume":"19 1","pages":""},"PeriodicalIF":20.8,"publicationDate":"2025-02-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143435495","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
Author Correction: A feeding-induced myokine modulates glucose homeostasis.
IF 18.9 1区 医学
Nature metabolism Pub Date : 2025-02-11 DOI: 10.1038/s42255-025-01231-y
Xiaoliu Shi, Xiao Hu, Xinlei Fang, Liangjie Jia, Fangchao Wei, Ying Peng, Menghao Liu, Aibo Gao, Ke Zhao, Fengyi Chen, Xiaoli Hu, Jie Hong, Guang Ning, Yongfeng Song, Jiqiu Wang, Yiguo Wang
{"title":"Author Correction: A feeding-induced myokine modulates glucose homeostasis.","authors":"Xiaoliu Shi, Xiao Hu, Xinlei Fang, Liangjie Jia, Fangchao Wei, Ying Peng, Menghao Liu, Aibo Gao, Ke Zhao, Fengyi Chen, Xiaoli Hu, Jie Hong, Guang Ning, Yongfeng Song, Jiqiu Wang, Yiguo Wang","doi":"10.1038/s42255-025-01231-y","DOIUrl":"https://doi.org/10.1038/s42255-025-01231-y","url":null,"abstract":"","PeriodicalId":19038,"journal":{"name":"Nature metabolism","volume":" ","pages":""},"PeriodicalIF":18.9,"publicationDate":"2025-02-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143399710","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
Author Correction: Cellular Feimin enhances exercise performance by suppressing muscle thermogenesis.
IF 18.9 1区 医学
Nature metabolism Pub Date : 2025-02-11 DOI: 10.1038/s42255-025-01232-x
Ying Peng, Liangjie Jia, Xiao Hu, Xiaoliu Shi, Xinlei Fang, Yifu Qiu, Zhenji Gan, Yiguo Wang
{"title":"Author Correction: Cellular Feimin enhances exercise performance by suppressing muscle thermogenesis.","authors":"Ying Peng, Liangjie Jia, Xiao Hu, Xiaoliu Shi, Xinlei Fang, Yifu Qiu, Zhenji Gan, Yiguo Wang","doi":"10.1038/s42255-025-01232-x","DOIUrl":"https://doi.org/10.1038/s42255-025-01232-x","url":null,"abstract":"","PeriodicalId":19038,"journal":{"name":"Nature metabolism","volume":" ","pages":""},"PeriodicalIF":18.9,"publicationDate":"2025-02-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143399674","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
Metabolic Messengers: small extracellular vesicles
IF 20.8 1区 医学
Nature metabolism Pub Date : 2025-02-07 DOI: 10.1038/s42255-024-01214-5
Theresa V. Rohm, Karina Cunha e Rocha, Jerrold M. Olefsky
{"title":"Metabolic Messengers: small extracellular vesicles","authors":"Theresa V. Rohm, Karina Cunha e Rocha, Jerrold M. Olefsky","doi":"10.1038/s42255-024-01214-5","DOIUrl":"https://doi.org/10.1038/s42255-024-01214-5","url":null,"abstract":"<p>Small extracellular vesicles (sEVs) are signalling molecules and biomarkers of cell status that govern a complex intraorgan and interorgan communication system through their cargo. Initially recognized as a waste disposal mechanism, they have emerged as important metabolic regulators. They transfer biological signals to recipient cells through their cargo content, and microRNAs (miRNAs) often mediate their metabolic effects. This review provides a concise overview of sEVs, specifically in the context of obesity-associated chronic inflammation and related metabolic disorders, describing their role as metabolic messengers, identifying their key sites of action and elucidating their mechanisms. We highlight studies that have shaped our understanding of sEV metabolism, address critical questions for future exploration, discuss the use of miRNAs as disease biomarkers and provide insights into the therapeutic potential of sEVs or specific miRNAs for treating metabolic diseases and related disorders in the future.</p>","PeriodicalId":19038,"journal":{"name":"Nature metabolism","volume":"78 1","pages":""},"PeriodicalIF":20.8,"publicationDate":"2025-02-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143258569","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
Translocation renal cell carcinoma says no to the Warburg effect 转移性肾细胞癌拒绝沃伯格效应
IF 20.8 1区 医学
Nature metabolism Pub Date : 2025-02-06 DOI: 10.1038/s42255-025-01216-x
Xingxiu Pan, Valentin Cracan
{"title":"Translocation renal cell carcinoma says no to the Warburg effect","authors":"Xingxiu Pan, Valentin Cracan","doi":"10.1038/s42255-025-01216-x","DOIUrl":"https://doi.org/10.1038/s42255-025-01216-x","url":null,"abstract":"A new study reveals that in drastic contrast to other cancer types, translocation renal cell carcinoma (tRCC) is transcriptionally rewired towards an oxidative phosphorylation (OXPHOS) state, which renders tRCC vulnerable to interventions that promote NADH reductive stress, highlighting how the maintenance of the optimal redox state in cancer can be therapeutically exploited.","PeriodicalId":19038,"journal":{"name":"Nature metabolism","volume":"76 1","pages":""},"PeriodicalIF":20.8,"publicationDate":"2025-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143191858","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
Oncogenic TFE3 fusions drive OXPHOS and confer metabolic vulnerabilities in translocation renal cell carcinoma
IF 20.8 1区 医学
Nature metabolism Pub Date : 2025-02-06 DOI: 10.1038/s42255-025-01218-9
Jiao Li, Kaimeng Huang, Meha Thakur, Fiona McBride, Ananthan Sadagopan, Daniel S. Gallant, Prateek Khanna, Yasmin Nabil Laimon, Bingchen Li, Razan Mohanna, Maolin Ge, Cary N. Weiss, Mingkee Achom, Qingru Xu, Sayed Matar, Gwo-Shu Mary Lee, Kun Huang, Miao Gui, Chin-Lee Wu, Kristine M. Cornejo, Toni K. Choueiri, Birgitta A. Ryback, Sabina Signoretti, Liron Bar-Peled, Srinivas R. Viswanathan
{"title":"Oncogenic TFE3 fusions drive OXPHOS and confer metabolic vulnerabilities in translocation renal cell carcinoma","authors":"Jiao Li, Kaimeng Huang, Meha Thakur, Fiona McBride, Ananthan Sadagopan, Daniel S. Gallant, Prateek Khanna, Yasmin Nabil Laimon, Bingchen Li, Razan Mohanna, Maolin Ge, Cary N. Weiss, Mingkee Achom, Qingru Xu, Sayed Matar, Gwo-Shu Mary Lee, Kun Huang, Miao Gui, Chin-Lee Wu, Kristine M. Cornejo, Toni K. Choueiri, Birgitta A. Ryback, Sabina Signoretti, Liron Bar-Peled, Srinivas R. Viswanathan","doi":"10.1038/s42255-025-01218-9","DOIUrl":"https://doi.org/10.1038/s42255-025-01218-9","url":null,"abstract":"<p>Translocation renal cell carcinoma (tRCC) is an aggressive subtype of kidney cancer driven by <i>TFE3</i> gene fusions, which act via poorly characterized downstream mechanisms. Here we report that TFE3 fusions transcriptionally rewire tRCCs toward oxidative phosphorylation (OXPHOS), contrasting with the highly glycolytic nature of most other renal cancers. Reliance on this TFE3 fusion-driven OXPHOS programme renders tRCCs vulnerable to NADH reductive stress, a metabolic stress induced by an imbalance of reducing equivalents. Genome-scale CRISPR screening identifies tRCC-selective vulnerabilities linked to this metabolic state, including <i>EGLN1</i>, which hydroxylates HIF-1α and targets it for proteolysis. Inhibition of EGLN1 compromises tRCC cell growth by stabilizing HIF-1α and promoting metabolic reprogramming away from OXPHOS, thus representing a vulnerability for OXPHOS-dependent tRCC cells. Our study defines tRCC as being dependent on a mitochondria-centred metabolic programme driven by TFE3 fusions and nominates EGLN1 inhibition as a therapeutic strategy in this cancer.</p>","PeriodicalId":19038,"journal":{"name":"Nature metabolism","volume":"40 1","pages":""},"PeriodicalIF":20.8,"publicationDate":"2025-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143191859","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
A future without needles: non-invasive glucose measurements in patients with diabetes
IF 20.8 1区 医学
Nature metabolism Pub Date : 2025-02-05 DOI: 10.1038/s42255-025-01221-0
Andreas L. Birkenfeld, Vasilis Ntziachristos
{"title":"A future without needles: non-invasive glucose measurements in patients with diabetes","authors":"Andreas L. Birkenfeld, Vasilis Ntziachristos","doi":"10.1038/s42255-025-01221-0","DOIUrl":"https://doi.org/10.1038/s42255-025-01221-0","url":null,"abstract":"Optical measurements through the skin are challenging because they usually represent averages across the various layers of skin that are illuminated. A study in Nature Metabolism uses a depth-selective variant of Raman spectroscopy to probe glucose levels specifically in the skin vasculature, and thereby achieves improved glucose sensing in humans.","PeriodicalId":19038,"journal":{"name":"Nature metabolism","volume":"61 1","pages":""},"PeriodicalIF":20.8,"publicationDate":"2025-02-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143125162","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
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