Nature metabolism最新文献

{"title":"GLP-1-mediated synaptic plasticity in feeding regulation is modulated by energy state","authors":"","doi":"10.1038/s42255-025-01304-y","DOIUrl":"10.1038/s42255-025-01304-y","url":null,"abstract":"Glucagon-like peptide 1 (GLP-1) receptor-expressing neurons in the paraventricular nucleus of the hypothalamus send descending excitatory projections to the dorsal vagal complex of the brainstem. GLP-1 signalling regulates synaptic transmission in this circuit in an energy state-dependent manner to control feeding and energy homeostasis.","PeriodicalId":19038,"journal":{"name":"Nature metabolism","volume":"7 7","pages":"1318-1319"},"PeriodicalIF":20.8,"publicationDate":"2025-06-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144252762","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":"State-dependent central synaptic regulation by GLP-1 is essential for energy homeostasis","authors":"Le Wang, Rohan H. Savani, Yi Lu, Matteo Bernabucci, Jorge Luis-Islas, Erin Park, Ishnoor Singh, Wei Xu, Abdelfattah El Ouaamari, Michael B. Wheeler, Harvey J. Grill, Mark A. Rossi, Zhiping P. Pang","doi":"10.1038/s42255-025-01305-x","DOIUrl":"10.1038/s42255-025-01305-x","url":null,"abstract":"Central glucagon-like peptide-1 (GLP-1), secreted by a distinct population of nucleus tractus solitarius neurons, suppresses feeding but the exact mechanisms of action in the brain remain unclear. Here, we investigate a descending circuit formed by GLP-1 receptor (GLP-1R) neurons in the paraventricular hypothalamic nucleus (PVNGLP-1R) projecting to the dorsal vagal complex (DVC) of the brain stem in mice. PVNGLP-1R→DVC synapses release glutamate and are augmented by GLP-1. Chemogenetic activation of PVNGLP-1R→DVC suppresses feeding. Under an energy deficit (that is, hunger) state, synaptic strength is weaker but is more profoundly augmented by GLP-1R activation than under energy-replete state. In an obese condition, the dynamic synaptic changes in this circuit are disrupted. Optogenetic activation of PVNGLP-1R→DVC projections suppresses food intake energy state dependently, and blocking its synaptic release or ablating GLP-1Rs in the presynaptic neurons impairs metabolic health. These findings indicate that the state-dependent synaptic regulation by GLP-1 in PVNGLP-1R→DVC descending circuit is important for energy homeostasis. In this paper, the authors describe the energy state-dependent regulation of the PVNGLP-1R to DVC circuit, resulting in altered food intake and metabolic health, mediated by GLP-1 receptor signalling.","PeriodicalId":19038,"journal":{"name":"Nature metabolism","volume":"7 7","pages":"1443-1458"},"PeriodicalIF":20.8,"publicationDate":"2025-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144211207","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":"Cysteine depletion triggers adipose tissue thermogenesis and weight loss","authors":"Aileen H. Lee, Lucie Orliaguet, Yun-Hee Youm, Rae Maeda, Tamara Dlugos, Yuanjiu Lei, Daniel Coman, Irina Shchukina, Prabhakar Sairam Andhey, Steven R. Smith, Eric Ravussin, Krisztian Stadler, Bandy Chen, Maxim N. Artyomov, Fahmeed Hyder, Tamas L. Horvath, Marc Schneeberger, Yuki Sugiura, Vishwa Deep Dixit","doi":"10.1038/s42255-025-01297-8","DOIUrl":"10.1038/s42255-025-01297-8","url":null,"abstract":"Caloric restriction and methionine restriction-driven enhanced lifespan and healthspan induces ‘browning’ of white adipose tissue, a metabolic response that increases heat production to defend core body temperature. However, how specific dietary amino acids control adipose thermogenesis is unknown. Here, we identified that weight loss induced by caloric restriction in humans reduces thiol-containing sulfur amino acid cysteine in white adipose tissue. Systemic cysteine depletion in mice causes lethal weight loss with increased fat utilization and browning of adipocytes that is rescued upon restoration of cysteine in diet. Mechanistically, cysteine-restriction-induced adipose browning and weight loss requires sympathetic nervous system-derived noradrenaline signalling via β3-adrenergic-receptors that is independent of FGF21 and UCP1. In obese mice, cysteine deprivation induced rapid adipose browning, increased energy expenditure leading to 30% weight loss and reversed metabolic inflammation. These findings establish that cysteine is essential for organismal metabolism as removal of cysteine in the host triggers adipose browning and rapid weight loss. The authors describe how reduced dietary availability and systemic loss of cysteine leads to adipose tissue browning and rapid weight loss in mice and humans.","PeriodicalId":19038,"journal":{"name":"Nature metabolism","volume":"7 6","pages":"1204-1222"},"PeriodicalIF":20.8,"publicationDate":"2025-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.comhttps://www.nature.com/articles/s42255-025-01297-8.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144201900","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":"β-hydroxybutyrate inhibits Plasmodium falciparum development and confers protection against malaria in mice","authors":"Zhiming Wei, Ning Jiang, Yiwei Zhang, Qilong Li, Ziwei Su, Yanxin Zhang, Kunying Lv, Yixin Yang, Tong Liu, Lu Sun, Kexin Zheng, Ang Li, Anni Feng, Xiaoyu Sang, Ying Feng, Ran Chen, Qijun Chen","doi":"10.1038/s42255-025-01302-0","DOIUrl":"10.1038/s42255-025-01302-0","url":null,"abstract":"Environmental factors restrict malaria parasite development, but the influence of host metabolic variations on the infectivity of the blood stage parasite is not fully understood. Here we show that mice on a ketogenic diet are completely protected from infection with the malaria parasite Plasmodium berghei. We further show that administration of the ketone body β-hydroxybutyrate (βOHB), but not of acetoacetate, increases survival of infected mice and inhibits proliferation of both P. berghei and Plasmodium falciparum in vitro. Administration of either a ketogenic diet or βOHB induces metabolic reprogramming in parasites, including reduced levels of nicotinamide adenine dinucleotide, which is associated with the downregulation of genes controlling parasite development, erythrocyte invasion and pathogenicity. Our data indicate that a ketogenic diet and the ketone body βOHB confer resistance to malaria in mice by causing developmental arrest of Plasmodium parasites, highlighting the potential of dietary and metabolic strategies to fight malarial infection. A ketogenic diet and the ketone body β-hydroxybutyrate are shown to confer resistance to malaria in mice by inducing metabolic reprogramming in Plasmodium parasites, suggesting a dietary strategy for malaria prevention.","PeriodicalId":19038,"journal":{"name":"Nature metabolism","volume":"7 7","pages":"1330-1343"},"PeriodicalIF":20.8,"publicationDate":"2025-05-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.comhttps://www.nature.com/articles/s42255-025-01302-0.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144122945","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":"A ketogenic diet halts malaria parasite growth","authors":"Temitope W. Ademolue, Lena Pernas","doi":"10.1038/s42255-025-01310-0","DOIUrl":"10.1038/s42255-025-01310-0","url":null,"abstract":"A new study reveals that the host-derived ketone body, β-hydroxybutyrate, protects against malaria in mice by inhibiting Plasmodium development. These findings highlight the anti-microbial potential of metabolic interventions.","PeriodicalId":19038,"journal":{"name":"Nature metabolism","volume":"7 7","pages":"1305-1306"},"PeriodicalIF":20.8,"publicationDate":"2025-05-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144122944","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":"Nuclear SREBP2 condensates regulate the transcriptional activation of lipogenic genes and cholesterol homeostasis","authors":"Mengqiang Xu, Shi-You Jiang, Shuocheng Tang, Meimei Zhu, Yueer Hu, Juewan Li, Jizhi Yan, Chenyang Qin, Dongxia Tan, Yang An, Yuxiu Qu, Bao-Liang Song, Hanhui Ma, Wei Qi","doi":"10.1038/s42255-025-01291-0","DOIUrl":"10.1038/s42255-025-01291-0","url":null,"abstract":"The precursor of sterol regulatory element-binding protein-2 (SREBP2) is a membrane-bound transcription factor regulating cholesterol biosynthesis. Under cholesterol-deficient conditions, mature SREBP2 is released from membrane-bound precursors through proteolytic cleavage and enters the nucleus. However, regulation of the transcriptional activity of nuclear SREBP2 (nSREBP2) is poorly understood. In the present study, we reported that nSREBP2 forms nuclear condensates through its amino-terminal, intrinsically disordered region (IDR) and works together with transcription coactivators, partly on superenhancers, for the transcriptional activation of SREBP2 target genes. Substitution of a conserved phenylalanine by alanine within the IDR abolishes the formation of nSREBP2 condensates and reduces its transcriptional activity. This can be effectively rescued by fusion with a phase separation driving FUS-IDR. Knock-in of the phenylalanine-to-alanine substitution in male mice compromises feeding-induced nSREBP2 activity and lowers hepatic and circulating cholesterol levels, underscoring the functional significance of nSREBP2 condensates. Together, the present study reveals that nuclear condensates driven by nSREBP2 N-terminal IDR facilitate the efficient activation of lipogenic genes and play an important role in cholesterol homeostasis. Nuclear SREBP2 forms nuclear condensates through its N-terminal intrinsically disordered region, which is essential for the transcriptional activation of lipogenic genes.","PeriodicalId":19038,"journal":{"name":"Nature metabolism","volume":"7 5","pages":"1034-1051"},"PeriodicalIF":20.8,"publicationDate":"2025-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144097673","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":"Cell-intrinsic metabolic phenotypes identified in patients with glioblastoma, using mass spectrometry imaging of 13C-labelled glucose metabolism","authors":"Anastasia Tsyben, Andreas Dannhorn, Gregory Hamm, Manthos Pitoulias, Dominique-Laurent Couturier, Ashley Sawle, Mayen Briggs, Alan J. Wright, Cara Brodie, Lee Mendil, Jodi L. Miller, Eleanor C. Williams, Lovisa Franzén, Grand De Jong, Tannia Gracia, Fani Memi, Omer Ali Bayraktar, Ram Adapa, Jyotsna Rao, Ariadna González-Fernández, CRUK Rosetta Grand Challenge Consortium, Josephine Bunch, Zoltan Takats, Simon T. Barry, Richard J. A. Goodwin, Richard Mair, Kevin M. Brindle","doi":"10.1038/s42255-025-01293-y","DOIUrl":"10.1038/s42255-025-01293-y","url":null,"abstract":"Transcriptomic studies have attempted to classify glioblastoma (GB) into subtypes that predict survival and have different therapeutic vulnerabilities1–3. Here we identified three metabolic subtypes: glycolytic, oxidative and a mix of glycolytic and oxidative, using mass spectrometry imaging of rapidly excised tumour sections from two patients with GB who were infused with [U-13C]glucose and from spatial transcriptomic analysis of contiguous sections. The phenotypes are not correlated with microenvironmental features, including proliferation rate, immune cell infiltration and vascularization, are retained when patient-derived cells are grown in vitro or as orthotopically implanted xenografts and are robust to changes in oxygen concentration, demonstrating their cell-intrinsic nature. The spatial extent of the regions occupied by cells displaying these distinct metabolic phenotypes is large enough to be detected using clinically applicable metabolic imaging techniques. A limitation of the study is that it is based on only two patient tumours, albeit on multiple sections, and therefore represents a proof-of-concept study. Tsyben et al. study the spatial distribution of labelled metabolites in glioblastoma samples from patients infused with 13C-glucose, using mass spectrometry imaging.","PeriodicalId":19038,"journal":{"name":"Nature metabolism","volume":"7 5","pages":"928-939"},"PeriodicalIF":20.8,"publicationDate":"2025-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.comhttps://www.nature.com/articles/s42255-025-01293-y.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144087872","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":"Mechanically sensitive MAPK signalling mediates resistance exercise-induced muscle growth","authors":"Sue C. Bodine, Craig A. Goodman","doi":"10.1038/s42255-025-01303-z","DOIUrl":"10.1038/s42255-025-01303-z","url":null,"abstract":"Understanding the molecular regulators of skeletal muscle mass is essential for the future development of therapies that promote muscle growth and/or inhibit muscle wasting. A new study shows that muscle-building resistance exercise in humans and mice activates a MAPK signalling pathway to increase protein synthesis and stimulate muscle hypertrophy.","PeriodicalId":19038,"journal":{"name":"Nature metabolism","volume":"7 7","pages":"1312-1314"},"PeriodicalIF":20.8,"publicationDate":"2025-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143979340","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":"Identification of a resistance-exercise-specific signalling pathway that drives skeletal muscle growth","authors":"Wenyuan G. Zhu, Aaron C. Q. Thomas, Gary M. Wilson, Chris McGlory, Jamie E. Hibbert, Corey GK. Flynn, Ramy K. A. Sayed, Hector G. Paez, Marius Meinhold, Kent W. Jorgenson, Jae-Sung You, Nathaniel D. Steinert, Kuan-Hung Lin, Martin J. MacInnis, Joshua J. Coon, Stuart M. Phillips, Troy A. Hornberger","doi":"10.1038/s42255-025-01298-7","DOIUrl":"10.1038/s42255-025-01298-7","url":null,"abstract":"Endurance and resistance exercise lead to distinct functional adaptations: the former increases aerobic capacity and the latter increases muscle mass. However, the signalling pathways that drive these adaptations are not well understood. Here we identify phosphorylation events that are differentially regulated by endurance and resistance exercise. Using a model of unilateral exercise in male participants and deep phosphoproteomic analyses, we find that a prolonged activation of a signalling pathway involving MKK3b/6, p38, MK2 and mTORC1 occurs specifically in response to resistance exercise. Follow-up studies in both male and female participants reveal that the resistance-exercise-induced activation of MKK3b is highly correlated with the induction of protein synthesis (R = 0.87). Additionally, we show that in mice, genetic activation of MKK3b is sufficient to induce signalling through p38, MK2 and mTORC1, along with an increase in protein synthesis and muscle fibre size. Overall, we identify core components of a signalling pathway that drives the growth-promoting effects of resistance exercise. This study demonstrates that the MKK3b/6 signalling pathway drives the skeletal muscle growth-promoting effects of resistance exercise.","PeriodicalId":19038,"journal":{"name":"Nature metabolism","volume":"7 7","pages":"1404-1423"},"PeriodicalIF":20.8,"publicationDate":"2025-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143979466","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":"Towards a consensus atlas of human and mouse adipose tissue at single-cell resolution","authors":"Anne Loft, Margo P. Emont, Ada Weinstock, Adeline Divoux, Adhideb Ghosh, Allon Wagner, Ann V. Hertzel, Babukrishna Maniyadath, Bart Deplancke, Boxiang Liu, Camilla Scheele, Carey Lumeng, Changhai Ding, Chenkai Ma, Christian Wolfrum, Clarissa Strieder-Barboza, Congru Li, Danh D. Truong, David A. Bernlohr, Elisabet Stener-Victorin, Erin E. Kershaw, Esti Yeger-Lotem, Farnaz Shamsi, Hannah X. Hui, Henrique Camara, Jiawei Zhong, Joanna Kalucka, Joseph A. Ludwig, Julie A. Semon, Jutta Jalkanen, Katie L. Whytock, Kyle D. Dumont, Lauren M. Sparks, Lindsey A. Muir, Lingzhao Fang, Lucas Massier, Luis R. Saraiva, Marc D. Beyer, Marc G. Jeschke, Marcelo A. Mori, Mariana Boroni, Martin J. Walsh, Mary-Elizabeth Patti, Matthew D. Lynes, Matthias Blüher, Mikael Rydén, Natnael Hamda, Nicole L. Solimini, Niklas Mejhert, Peng Gao, Rana K. Gupta, Rinki Murphy, Saeed Pirouzpanah, Silvia Corvera, Su’an Tang, Swapan K. Das, Søren F. Schmidt, Tao Zhang, Theodore M. Nelson, Timothy E. O’Sullivan, Vissarion Efthymiou, Wenjing Wang, Yihan Tong, Yu-Hua Tseng, Susanne Mandrup, Evan D. Rosen","doi":"10.1038/s42255-025-01296-9","DOIUrl":"10.1038/s42255-025-01296-9","url":null,"abstract":"Adipose tissue (AT) is a complex connective tissue with a high relative proportion of adipocytes, which are specialized cells with the ability to store lipids in large droplets. AT is found in multiple discrete depots throughout the body, where it serves as the primary repository for excess calories. In addition, AT has an important role in functions as diverse as insulation, immunity and regulation of metabolic homeostasis. The Human Cell Atlas Adipose Bionetwork was established to support the generation of single-cell atlases of human AT as well as the development of unified approaches and consensus for cell annotation. Here, we provide a first roadmap from this bionetwork, including our suggested cell annotations for humans and mice, with the aim of describing the state of the field and providing guidelines for the production, analysis, interpretation and presentation of AT single-cell data. In this Review, the authors present a roadmap towards achieving consensus on development, analysis and interpretation of single-cell transcriptomics data in adipose tissue, including discussion of roadblocks, best practices and ideal cell-type markers for annotation of adipose tissue cell types in mice and humans.","PeriodicalId":19038,"journal":{"name":"Nature metabolism","volume":"7 5","pages":"875-894"},"PeriodicalIF":20.8,"publicationDate":"2025-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.comhttps://www.nature.com/articles/s42255-025-01296-9.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143940087","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}