Nature metabolism最新文献

{"title":"Mechanosensation of the heart and gut elicits hypometabolism and vigilance in mice","authors":"Karen A. Scott, Yalun Tan, Dominique N. Johnson, Khalid Elsaafien, Caitlin Baumer-Harrison, Rebeca Méndez-Hernández, Matthew K. Kirchner, Sophia A. Eikenberry, Jessica M. Sa, Javier E. Stern, Guillaume de Lartigue, Annette D. de Kloet, Eric G. Krause","doi":"10.1038/s42255-024-01205-6","DOIUrl":"https://doi.org/10.1038/s42255-024-01205-6","url":null,"abstract":"<p>Interoception broadly refers to awareness of one’s internal milieu. Although the importance of the body-to-brain communication that underlies interoception is implicit, the vagal afferent signalling and corresponding brain circuits that shape perception of the viscera are not entirely clear. Here, we use mice to parse neural circuits subserving interoception of the heart and gut. We determine that vagal sensory neurons expressing the oxytocin receptor (<i>Oxtr</i>), referred to as NG^Oxtr, send projections to cardiovascular or gastrointestinal tissues and exhibit molecular and structural features indicative of mechanosensation. Chemogenetic excitation of NG^Oxtr decreases food and water consumption, and remarkably, produces a torpor-like phenotype characterized by reductions in cardiac output, body temperature and energy expenditure. Chemogenetic excitation of NG^Oxtr also creates patterns of brain activity associated with augmented hypothalamic–pituitary–adrenal axis activity and behavioural indices of vigilance. Recurrent excitation of NG^Oxtr suppresses food intake and lowers body mass, indicating that mechanosensation of the heart and gut can exert enduring effects on energy balance. These findings suggest that the sensation of vascular stretch and gastrointestinal distention may have profound effects on whole-body metabolism and, possibly, mental health.</p>","PeriodicalId":19038,"journal":{"name":"Nature metabolism","volume":"83 1","pages":""},"PeriodicalIF":20.8,"publicationDate":"2025-01-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142987295","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}

{"title":"Mechanosensitive neurons innervating the gut and heart control metabolic and emotional state","authors":"","doi":"10.1038/s42255-024-01208-3","DOIUrl":"https://doi.org/10.1038/s42255-024-01208-3","url":null,"abstract":"Body-to-brain communication profoundly affects physiology and behaviour. Sensory neurons that express oxytocin receptors relay mechanical stretch of the gut and heart to the brain. Surprisingly, simultaneous firing of these neurons reliably elicits a hypometabolic state that resembles torpor. These observations could have implications ranging from cardiometabolic therapeutics to space travel.","PeriodicalId":19038,"journal":{"name":"Nature metabolism","volume":"54 1","pages":""},"PeriodicalIF":20.8,"publicationDate":"2025-01-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142987292","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}

{"title":"Proline exacerbates hepatic gluconeogenesis via paraspeckle-dependent mRNA retention","authors":"Yurong Zhao, Xinxin Chai, Junxuan Peng, Yi Zhu, Rong Dong, Junwei He, Linghao Xia, Sishuo Liu, Jingzhou Chen, Zhengping Xu, Chi Luo, Jinghao Sheng","doi":"10.1038/s42255-024-01206-5","DOIUrl":"https://doi.org/10.1038/s42255-024-01206-5","url":null,"abstract":"<p>Type 2 diabetes (T2D) is a global health issue characterized by abnormal blood glucose levels and is often associated with excessive hepatic gluconeogenesis. Increased circulating non-essential amino acids (NEAAs) are consistently observed in individuals with T2D; however, the specific contribution of each amino acid to T2D pathogenesis remains less understood. Here, we report an unexpected role of the NEAA proline in coordinating hepatic glucose metabolism by modulating paraspeckle, a nuclear structure scaffolded by the long non-coding RNA Neat1. Mechanistically, proline diminished paraspeckles in hepatocytes, liberating the retained mRNA species into cytoplasm for translation, including the mRNAs of <i>Ppargc1a</i> and <i>Foxo1</i>, contributing to enhanced gluconeogenesis and hyperglycaemia. We further demonstrated that the proline–paraspeckle–mRNA retention axis existed in diabetic liver samples, and intervening in this axis via paraspeckle restoration substantially alleviated hyperglycaemia in both female and male diabetic mouse models. Collectively, our results not only delineated a previously unappreciated proline-instigated, paraspeckle-dependent mRNA-retention mechanism regulating gluconeogenesis, but also spotlighted proline and paraspeckle as potential targets for managing hyperglycaemia.</p>","PeriodicalId":19038,"journal":{"name":"Nature metabolism","volume":"74 2 Pt 1 1","pages":""},"PeriodicalIF":20.8,"publicationDate":"2025-01-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142986009","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}

{"title":"Recommendations for mitochondria transfer and transplantation nomenclature and characterization","authors":"Jonathan R. Brestoff,&nbsp;Keshav K. Singh,&nbsp;Katia Aquilano,&nbsp;Lance B. Becker,&nbsp;Michael V. Berridge,&nbsp;Eric Boilard,&nbsp;Andrés Caicedo,&nbsp;Clair Crewe,&nbsp;José Antonio Enríquez,&nbsp;Jianqing Gao,&nbsp;Åsa B. Gustafsson,&nbsp;Kazuhide Hayakawa,&nbsp;Maroun Khoury,&nbsp;Yun-Sil Lee,&nbsp;Daniele Lettieri-Barbato,&nbsp;Patricia Luz-Crawford,&nbsp;Heidi M. McBride,&nbsp;James D. McCully,&nbsp;Ritsuko Nakai,&nbsp;Jiri Neuzil,&nbsp;Martin Picard,&nbsp;Alexander G. Rabchevsky,&nbsp;Anne-Marie Rodriguez,&nbsp;Shiladitya Sengupta,&nbsp;Alexander J. Sercel,&nbsp;Toshio Suda,&nbsp;Michael A. Teitell,&nbsp;Alain R. Thierry,&nbsp;Rong Tian,&nbsp;Melanie Walker,&nbsp;Minghao Zheng","doi":"10.1038/s42255-024-01200-x","DOIUrl":"10.1038/s42255-024-01200-x","url":null,"abstract":"Intercellular mitochondria transfer is an evolutionarily conserved process in which one cell delivers some of their mitochondria to another cell in the absence of cell division. This process has diverse functions depending on the cell types involved and physiological or disease context. Although mitochondria transfer was first shown to provide metabolic support to acceptor cells, recent studies have revealed diverse functions of mitochondria transfer, including, but not limited to, the maintenance of mitochondria quality of the donor cell and the regulation of tissue homeostasis and remodelling. Many mitochondria-transfer mechanisms have been described using a variety of names, generating confusion about mitochondria transfer biology. Furthermore, several therapeutic approaches involving mitochondria-transfer biology have emerged, including mitochondria transplantation and cellular engineering using isolated mitochondria. In this Consensus Statement, we define relevant terminology and propose a nomenclature framework to describe mitochondria transfer and transplantation as a foundation for further development by the community as this dynamic field of research continues to evolve. This Consensus Statement provides a nomenclature framework and experimental recommendations for studying mitochondrial transfer and transplantation.","PeriodicalId":19038,"journal":{"name":"Nature metabolism","volume":"7 1","pages":"53-67"},"PeriodicalIF":18.9,"publicationDate":"2025-01-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s42255-024-01200-x.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142986010","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}

{"title":"Separate orexigenic hippocampal ensembles shape dietary choice by enhancing contextual memory and motivation","authors":"Mingxin Yang, Arashdeep Singh, Alan de Araujo, Molly McDougle, Hillary Ellis, Léa Décarie-Spain, Scott E. Kanoski, Guillaume de Lartigue","doi":"10.1038/s42255-024-01194-6","DOIUrl":"https://doi.org/10.1038/s42255-024-01194-6","url":null,"abstract":"<p>The hippocampus (HPC) has emerged as a critical player in the control of food intake, beyond its well-known role in memory. While previous studies have primarily associated the HPC with food intake inhibition, recent research suggests a role in appetitive processes. Here we identified spatially distinct neuronal populations within the dorsal HPC (dHPC) that respond to either fats or sugars, potent natural reinforcers that contribute to obesity development. Using activity-dependent genetic capture of nutrient-responsive dHPC neurons, we demonstrate a causal role of both populations in promoting nutrient-specific intake through different mechanisms. Sugar-responsive neurons encoded spatial memory for sugar location, whereas fat-responsive neurons selectively enhanced the preference and motivation for fat intake. Importantly, stimulation of either nutrient-responsive dHPC neurons increased food intake, while ablation differentially impacted obesogenic diet consumption and prevented diet-induced weight gain. Collectively, these findings uncover previously unknown orexigenic circuits underlying macronutrient-specific consumption and provide a foundation for developing potential obesity treatments.</p>","PeriodicalId":19038,"journal":{"name":"Nature metabolism","volume":"1 1","pages":""},"PeriodicalIF":20.8,"publicationDate":"2025-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142981354","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}

{"title":"Feeding the hippocampus … with specific nutrients","authors":"Pierre Trifilieff, Guillaume Ferreira","doi":"10.1038/s42255-024-01180-y","DOIUrl":"https://doi.org/10.1038/s42255-024-01180-y","url":null,"abstract":"The hippocampus is well known to control cognitive processes, but increasing evidence emphasizes its central role in the regulation of feeding behaviour. Yang et al. unravel segregated hippocampal populations responding to either sugar or fat that participate in memory and motivational control of food intake.","PeriodicalId":19038,"journal":{"name":"Nature metabolism","volume":"17 1","pages":""},"PeriodicalIF":20.8,"publicationDate":"2025-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142981353","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}

{"title":"Autophagy regulator ATG5 preserves cerebellar function by safeguarding its glycolytic activity","authors":"Janine Tutas, Marianna Tolve, Ebru Özer-Yildiz, Lotte Ickert, Ines Klein, Quinn Silverman, Filip Liebsch, Frederik Dethloff, Patrick Giavalisco, Heike Endepols, Theodoros Georgomanolis, Bernd Neumaier, Alexander Drzezga, Guenter Schwarz, Bernard Thorens, Graziana Gatto, Christian Frezza, Natalia L. Kononenko","doi":"10.1038/s42255-024-01196-4","DOIUrl":"https://doi.org/10.1038/s42255-024-01196-4","url":null,"abstract":"<p>Dysfunctions in autophagy, a cellular mechanism for breaking down components within lysosomes, often lead to neurodegeneration. The specific mechanisms underlying neuronal vulnerability due to autophagy dysfunction remain elusive. Here we show that autophagy contributes to cerebellar Purkinje cell (PC) survival by safeguarding their glycolytic activity. Outside the conventional housekeeping role, autophagy is also involved in the ATG5-mediated regulation of glucose transporter 2 (GLUT2) levels during cerebellar maturation. Autophagy-deficient PCs exhibit GLUT2 accumulation on the plasma membrane, along with increased glucose uptake and alterations in glycolysis. We identify lysophosphatidic acid and serine as glycolytic intermediates that trigger PC death and demonstrate that the deletion of GLUT2 in ATG5-deficient mice mitigates PC neurodegeneration and rescues their ataxic gait. Taken together, this work reveals a mechanism for regulating GLUT2 levels in neurons and provides insights into the neuroprotective role of autophagy by controlling glucose homeostasis in the brain.</p>","PeriodicalId":19038,"journal":{"name":"Nature metabolism","volume":"41 1","pages":""},"PeriodicalIF":20.8,"publicationDate":"2025-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142981355","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}

{"title":"Multiplex genome editing eliminates lactate production without impacting growth rate in mammalian cells","authors":"Hooman Hefzi,&nbsp;Iván Martínez-Monge,&nbsp;Igor Marin de Mas,&nbsp;Nicholas Luke Cowie,&nbsp;Alejandro Gomez Toledo,&nbsp;Soo Min Noh,&nbsp;Karen Julie la Cour Karottki,&nbsp;Marianne Decker,&nbsp;Johnny Arnsdorf,&nbsp;Jose Manuel Camacho-Zaragoza,&nbsp;Stefan Kol,&nbsp;Sanne Schoffelen,&nbsp;Nuša Pristovšek,&nbsp;Anders Holmgaard Hansen,&nbsp;Antonio A. Miguez,&nbsp;Sara Petersen Bjørn,&nbsp;Karen Kathrine Brøndum,&nbsp;Elham Maria Javidi,&nbsp;Kristian Lund Jensen,&nbsp;Laura Stangl,&nbsp;Emanuel Kreidl,&nbsp;Thomas Beuchert Kallehauge,&nbsp;Daniel Ley,&nbsp;Patrice Ménard,&nbsp;Helle Munck Petersen,&nbsp;Zulfiya Sukhova,&nbsp;Anton Bauer,&nbsp;Emilio Casanova,&nbsp;Niall Barron,&nbsp;Johan Malmström,&nbsp;Lars K. Nielsen,&nbsp;Gyun Min Lee,&nbsp;Helene Faustrup Kildegaard,&nbsp;Bjørn G. Voldborg,&nbsp;Nathan E. Lewis","doi":"10.1038/s42255-024-01193-7","DOIUrl":"10.1038/s42255-024-01193-7","url":null,"abstract":"The Warburg effect, which describes the fermentation of glucose to lactate even in the presence of oxygen, is ubiquitous in proliferative mammalian cells, including cancer cells, but poses challenges for biopharmaceutical production as lactate accumulation inhibits cell growth and protein production. Previous efforts to eliminate lactate production in cells for bioprocessing have failed as lactate dehydrogenase is essential for cell growth. Here, we effectively eliminate lactate production in Chinese hamster ovary and in the human embryonic kidney cell line HEK293 by simultaneous knockout of lactate dehydrogenases and pyruvate dehydrogenase kinases, thereby removing a negative feedback loop that typically inhibits pyruvate conversion to acetyl-CoA. These cells, which we refer to as Warburg-null cells, maintain wild-type growth rates while producing negligible lactate, show a compensatory increase in oxygen consumption, near total reliance on oxidative metabolism, and higher cell densities in fed-batch cell culture. Warburg-null cells remain amenable for production of diverse biotherapeutic proteins, reaching industrially relevant titres and maintaining product glycosylation. The ability to eliminate lactate production may be useful for biotherapeutic production and provides a tool for investigating a common metabolic phenomenon. Hefzi et al. engineer cells to nearly eliminate lactate production and increase mitochondrial use of pyruvate by deleting both lactate dehydrogenases and pyruvate dehydrogenase kinases with the goal of circumventing pH and osmolarity issues that arise in bioreactor-based production of biopharmaceuticals.","PeriodicalId":19038,"journal":{"name":"Nature metabolism","volume":"7 1","pages":"212-227"},"PeriodicalIF":18.9,"publicationDate":"2025-01-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142975087","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}

{"title":"Diabetes in China: epidemiology, pathophysiology and multi-omics","authors":"Weiping Jia,&nbsp;Juliana CN Chan,&nbsp;Tien Y. Wong,&nbsp;Edwin B. Fisher","doi":"10.1038/s42255-024-01190-w","DOIUrl":"10.1038/s42255-024-01190-w","url":null,"abstract":"Although diabetes is now a global epidemic, China has the highest number of affected people, presenting profound public health and socioeconomic challenges. In China, rapid ecological and lifestyle shifts have dramatically altered diabetes epidemiology and risk factors. In this Review, we summarize the epidemiological trends and the impact of traditional and emerging risk factors on Chinese diabetes prevalence. We also explore recent genetic, metagenomic and metabolomic studies of diabetes in Chinese, highlighting their role in pathogenesis and clinical management. Although heterogeneity across these multidimensional areas poses major analytic challenges in classifying patterns or features, they have also provided an opportunity to increase the accuracy and specificity of diagnosis for personalized treatment and prevention. National strategies and ongoing research are essential for improving diabetes detection, prevention and control, and for personalizing care to alleviate societal impacts and maintain quality of life. In this Review, the authors summarize epidemiological trends of type 2 diabetes in China, discuss unique risk factors contributing to diabetes risk in the Chinese population and highlight how recent advances from multi-omics studies can affect treatment of diabetes in China.","PeriodicalId":19038,"journal":{"name":"Nature metabolism","volume":"7 1","pages":"16-34"},"PeriodicalIF":18.9,"publicationDate":"2025-01-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142974544","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}

{"title":"Early prediction of healthy ageing and age-related diseases using blood protein biomarkers","authors":"","doi":"10.1038/s42255-024-01199-1","DOIUrl":"10.1038/s42255-024-01199-1","url":null,"abstract":"Ageing is associated with proteomic changes in the blood. However, most research on the ageing blood proteome is cross-sectional in nature. Using a longitudinal analysis, we identified 86 ageing-related blood proteins and further revealed a subset of 22 protein biomarkers that, in combination, predict healthy ageing status and age-related cardiometabolic disease risk.","PeriodicalId":19038,"journal":{"name":"Nature metabolism","volume":"7 1","pages":"14-15"},"PeriodicalIF":18.9,"publicationDate":"2025-01-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142968262","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}