Nature metabolism最新文献

Author Correction: Intestinal TM6SF2 protects against metabolic dysfunction-associated steatohepatitis through the gut-liver axis. 作者更正：肠道TM6SF2通过肠-肝轴保护代谢功能障碍相关的脂肪性肝炎。

IF 18.9 1区医学

Nature metabolism Pub Date : 2025-01-21 DOI: 10.1038/s42255-025-01215-y

Xiang Zhang, Harry Cheuk-Hay Lau, Suki Ha, Chuanfa Liu, Cong Liang, Hye Won Lee, Queena Wing-Yin Ng, Yi Zhao, Fenfen Ji, Yunfei Zhou, Yasi Pan, Yang Song, Yating Zhang, Jennie Ching Yin Lo, Alvin Ho Kwan Cheung, Jianfeng Wu, Xiaoxing Li, Hongzhi Xu, Chi Chun Wong, Vincent Wai-Sun Wong, Jun Yu

引用次数: 0

Aldolase A: the broker of glycolysis 醛缩酶A：糖酵解的中间人

IF 20.8 1区医学

Nature metabolism Pub Date : 2025-01-20 DOI: 10.1038/s42255-024-01202-9

Luiza Martins Nascentes Melo, Feyza Cansiz, Alpaslan Tasdogan

引用次数: 0

Targeting aldolase A in hepatocellular carcinoma leads to imbalanced glycolysis and energy stress due to uncontrolled FBP accumulation 在肝细胞癌中靶向醛缩酶A会导致不平衡的糖酵解和能量应激，因为不受控制的FBP积累

IF 20.8 1区医学

Nature metabolism Pub Date : 2025-01-20 DOI: 10.1038/s42255-024-01201-w

Marteinn T. Snaebjornsson, Philipp Poeller, Daria Komkova, Florian Röhrig, Lisa Schlicker, Alina M. Winkelkotte, Adriano B. Chaves-Filho, Kamal M. Al-Shami, Carolina Dehesa Caballero, Ioanna Koltsaki, Felix C. E. Vogel, Roberto Carlos Frias-Soler, Ramona Rudalska, Jessica D. Schwarz, Elmar Wolf, Daniel Dauch, Ralf Steuer, Almut Schulze

{"title":"Targeting aldolase A in hepatocellular carcinoma leads to imbalanced glycolysis and energy stress due to uncontrolled FBP accumulation","authors":"Marteinn T. Snaebjornsson, Philipp Poeller, Daria Komkova, Florian Röhrig, Lisa Schlicker, Alina M. Winkelkotte, Adriano B. Chaves-Filho, Kamal M. Al-Shami, Carolina Dehesa Caballero, Ioanna Koltsaki, Felix C. E. Vogel, Roberto Carlos Frias-Soler, Ramona Rudalska, Jessica D. Schwarz, Elmar Wolf, Daniel Dauch, Ralf Steuer, Almut Schulze","doi":"10.1038/s42255-024-01201-w","DOIUrl":"https://doi.org/10.1038/s42255-024-01201-w","url":null,"abstract":"Increased glycolytic flux is a hallmark of cancer; however, an increasing body of evidence indicates that glycolytic ATP production may be dispensable in cancer, as metabolic plasticity allows cancer cells to readily adapt to disruption of glycolysis by increasing ATP production via oxidative phosphorylation. Using functional genomic screening, we show here that liver cancer cells show a unique sensitivity toward aldolase A (ALDOA) depletion. Targeting glycolysis by disrupting the catalytic activity of ALDOA led to severe energy stress and cell cycle arrest in murine and human hepatocellular carcinoma cell lines. With a combination of metabolic flux analysis, metabolomics, stable-isotope tracing and mathematical modelling, we demonstrate that inhibiting ALDOA induced a state of imbalanced glycolysis in which the investment phase outpaced the payoff phase. Targeting ALDOA effectively converted glycolysis from an energy producing into an energy-consuming process. Moreover, we found that depletion of ALDOA extended survival and reduced cancer cell proliferation in an animal model of hepatocellular carcinoma. Thus, our findings indicate that induction of imbalanced glycolysis by targeting ALDOA presents a unique opportunity to overcome the inherent metabolic plasticity of cancer cells.","PeriodicalId":19038,"journal":{"name":"Nature metabolism","volume":"49 1","pages":""},"PeriodicalIF":20.8,"publicationDate":"2025-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142989920","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

Mechanosensation of the heart and gut elicits hypometabolism and vigilance in mice 心脏和肠道的机械感觉引起小鼠的低代谢和警觉性

IF 20.8 1区医学

Nature metabolism Pub Date : 2025-01-17 DOI: 10.1038/s42255-024-01205-6

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

{"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":"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 (Oxtr), referred to as NGOxtr, send projections to cardiovascular or gastrointestinal tissues and exhibit molecular and structural features indicative of mechanosensation. Chemogenetic excitation of NGOxtr 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 NGOxtr also creates patterns of brain activity associated with augmented hypothalamic–pituitary–adrenal axis activity and behavioural indices of vigilance. Recurrent excitation of NGOxtr 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.","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}

引用次数: 0

Mechanosensitive neurons innervating the gut and heart control metabolic and emotional state 支配肠道和心脏的机械敏感神经元控制着代谢和情绪状态

IF 20.8 1区医学

Nature metabolism Pub Date : 2025-01-17 DOI: 10.1038/s42255-024-01208-3

引用次数: 0

Proline exacerbates hepatic gluconeogenesis via paraspeckle-dependent mRNA retention 脯氨酸通过斑旁依赖性mRNA保留加剧肝脏糖异生

IF 20.8 1区医学

Nature metabolism Pub Date : 2025-01-16 DOI: 10.1038/s42255-024-01206-5

Yurong Zhao, Xinxin Chai, Junxuan Peng, Yi Zhu, Rong Dong, Junwei He, Linghao Xia, Sishuo Liu, Jingzhou Chen, Zhengping Xu, Chi Luo, Jinghao Sheng

{"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":"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 Ppargc1a and Foxo1, 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.","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}

引用次数: 0

Recommendations for mitochondria transfer and transplantation nomenclature and characterization 线粒体转移和移植的命名和表征建议

IF 20.8 1区医学

Nature metabolism Pub Date : 2025-01-16 DOI: 10.1038/s42255-024-01200-x

Jonathan R. Brestoff, Keshav K. Singh, Katia Aquilano, Lance B. Becker, Michael V. Berridge, Eric Boilard, Andrés Caicedo, Clair Crewe, José Antonio Enríquez, Jianqing Gao, Åsa B. Gustafsson, Kazuhide Hayakawa, Maroun Khoury, Yun-Sil Lee, Daniele Lettieri-Barbato, Patricia Luz-Crawford, Heidi M. McBride, James D. McCully, Ritsuko Nakai, Jiri Neuzil, Martin Picard, Alexander G. Rabchevsky, Anne-Marie Rodriguez, Shiladitya Sengupta, Alexander J. Sercel, Toshio Suda, Michael A. Teitell, Alain R. Thierry, Rong Tian, Melanie Walker, Minghao Zheng

{"title":"Recommendations for mitochondria transfer and transplantation nomenclature and characterization","authors":"Jonathan R. Brestoff, Keshav K. Singh, Katia Aquilano, Lance B. Becker, Michael V. Berridge, Eric Boilard, Andrés Caicedo, Clair Crewe, José Antonio Enríquez, Jianqing Gao, Åsa B. Gustafsson, Kazuhide Hayakawa, Maroun Khoury, Yun-Sil Lee, Daniele Lettieri-Barbato, Patricia Luz-Crawford, Heidi M. McBride, James D. McCully, Ritsuko Nakai, Jiri Neuzil, Martin Picard, Alexander G. Rabchevsky, Anne-Marie Rodriguez, Shiladitya Sengupta, Alexander J. Sercel, Toshio Suda, Michael A. Teitell, Alain R. Thierry, Rong Tian, Melanie Walker, Minghao Zheng","doi":"10.1038/s42255-024-01200-x","DOIUrl":"https://doi.org/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.","PeriodicalId":19038,"journal":{"name":"Nature metabolism","volume":"43 1","pages":""},"PeriodicalIF":20.8,"publicationDate":"2025-01-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","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":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Separate orexigenic hippocampal ensembles shape dietary choice by enhancing contextual memory and motivation 单独的含氧海马体通过增强情境记忆和动机来塑造饮食选择

IF 20.8 1区医学

Nature metabolism Pub Date : 2025-01-15 DOI: 10.1038/s42255-024-01194-6

Mingxin Yang, Arashdeep Singh, Alan de Araujo, Molly McDougle, Hillary Ellis, Léa Décarie-Spain, Scott E. Kanoski, Guillaume de Lartigue

{"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":"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.","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}

引用次数: 0

Feeding the hippocampus … with specific nutrients 给海马体提供特定的营养

IF 20.8 1区医学

Nature metabolism Pub Date : 2025-01-15 DOI: 10.1038/s42255-024-01180-y

Pierre Trifilieff, Guillaume Ferreira

引用次数: 0

Autophagy regulator ATG5 preserves cerebellar function by safeguarding its glycolytic activity 自噬调节因子ATG5通过保护其糖酵解活性来保护小脑功能

IF 20.8 1区医学

Nature metabolism Pub Date : 2025-01-15 DOI: 10.1038/s42255-024-01196-4

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

{"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":"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.","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}

引用次数: 0