Cell metabolism最新文献

Oxidative stress-induced astrocytic collagen biosynthesis drives glial barrier formation and neuronal death in ischemic stroke 氧化应激诱导的星形胶质细胞胶原生物合成驱动缺血性卒中的胶质屏障形成和神经元死亡

IF 29 1区生物学

Cell metabolism Pub Date : 2026-04-27 DOI: 10.1016/j.cmet.2026.04.001

Jae-Hun Lee, In-Young Hwang, Hyun Jun Jang, Hyeon-Gu Yeo, Jiwoon Lim, Jinyoung Won, Benedict Reve Delmo, Myungju Kim, Eunji Lee, Woojin Won, Elijah Hwejin Lee, Ki Jung Kim, Tai Young Kim, Jiwoong Jung, Kyung Seob Lim, Chang-Yeop Jeon, Junghyung Park, Minji Kim, Jisun Min, Hyerin Jang, C. Justin Lee

{"title":"Oxidative stress-induced astrocytic collagen biosynthesis drives glial barrier formation and neuronal death in ischemic stroke","authors":"Jae-Hun Lee, In-Young Hwang, Hyun Jun Jang, Hyeon-Gu Yeo, Jiwoon Lim, Jinyoung Won, Benedict Reve Delmo, Myungju Kim, Eunji Lee, Woojin Won, Elijah Hwejin Lee, Ki Jung Kim, Tai Young Kim, Jiwoong Jung, Kyung Seob Lim, Chang-Yeop Jeon, Junghyung Park, Minji Kim, Jisun Min, Hyerin Jang, C. Justin Lee","doi":"10.1016/j.cmet.2026.04.001","DOIUrl":"https://doi.org/10.1016/j.cmet.2026.04.001","url":null,"abstract":"Astrocytes regulate brain metabolism and homeostasis, but how oxidative stress reshapes astrocytic metabolism to drive neuronal damage remains unclear. Here, we demonstrate that oxidative stress turns on astrocytic type I collagen (COL1) production via a redox-glycosylation coupling mechanism. Hydrogen peroxide (H2O2) suppresses miR-29 and enhances fucosyltransferase 8 (FUT8)-mediated core fucosylation, integrating post-transcriptional and glycosylation-dependent regulation of COL1. Astrocyte-derived COL1 activates integrin signaling and promotes neuronal death. In a photothrombotic stroke model, an H2O2 surge induces astrogliosis, glycosylation remodeling, and COL1 expression, leading to glial barrier formation, neuronal loss, and neurological deficits. These pathological cascades are mitigated by astrocyte-specific silencing of COL1 or FUT8 or by KDS12025, a peroxidase enhancer that reduces H2O2 burden. Notably, KDS12025 exerts potent neuroprotection in a non-human primate stroke model. Together, our findings identify an unprecedented astrocytic metabolic pathway linking oxidative stress to glycosylation-driven COL1 production, highlighting the H2O2 surge, astrocytic COL1, and FUT8 as promising therapeutic targets for recovery after stroke.","PeriodicalId":9840,"journal":{"name":"Cell metabolism","volume":"35 1","pages":""},"PeriodicalIF":29.0,"publicationDate":"2026-04-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147751599","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

DGAT-driven futile lipid cycling has a pronounced, yet concealed, thermogenic function dgat驱动的无用脂质循环具有明显但隐蔽的产热功能

IF 29 1区生物学

Cell metabolism Pub Date : 2026-04-22 DOI: 10.1016/j.cmet.2026.04.007

Anand Kumar Sharma, Radhika Khandelwal, Jelena Zurkovic, Fen Long, Tongtong Wang, Revati S. Dewal, Chunyan Wu, Adhideb Ghosh, Klug Manuel, Alaa Othman, Chandramohan Chitraju, Robert V. Farese Jr., Tobias C. Walther, Miroslav Balaz, Christoph Thiele, Christian Wolfrum

引用次数: 0

Mitochondrial metabolism regulates the immunogenic responsiveness of dendritic cells 线粒体代谢调节树突状细胞的免疫原性反应

IF 29 1区生物学

Cell metabolism Pub Date : 2026-04-22 DOI: 10.1016/j.cmet.2026.04.010

Ignacio Heras-Murillo, Diego Mañanes, Josep Calafell-Segura, Adrián Belinchón García, Clara Borràs-Eroles, Pablo Munné, Annalaura Mastrangelo, Sarai Martínez-Cano, Pablo Hernansanz-Agustín, María A. Zuriaga, José J. Fuster, Marten Szibor, Ignacio Melero, José Antonio Enríquez, Navdeep S. Chandel, Esteban Ballestar, Stefanie K. Wculek, David Sancho

引用次数: 0

Cav3.1 is a neuronal leucine sensor that mediates satiety and weight loss in response to dietary protein Cav3.1是一种神经元亮氨酸传感器，介导对膳食蛋白质的饱腹感和体重减轻

IF 29 1区生物学

Cell metabolism Pub Date : 2026-04-22 DOI: 10.1016/j.cmet.2026.03.017

Anthony H. Tsang, Nicholas Heeley, Constanza Alcaino, Eunsang Hwang, Brian Y. Lam, Taufiq Rahman, Tamana Darwish, Danae Nuzzaci, Richard G. Kay, Amar Sarkar, Ruiyan Wang, Nihal Basha, Austin Punnoose, Peter Kirwan, Marcella Ma, Giles S. Yeo, Florian T. Merkle, Fiona M. Gribble, Frank Reinmann, Kevin W. Williams, Clémence Blouet

{"title":"Cav3.1 is a neuronal leucine sensor that mediates satiety and weight loss in response to dietary protein","authors":"Anthony H. Tsang, Nicholas Heeley, Constanza Alcaino, Eunsang Hwang, Brian Y. Lam, Taufiq Rahman, Tamana Darwish, Danae Nuzzaci, Richard G. Kay, Amar Sarkar, Ruiyan Wang, Nihal Basha, Austin Punnoose, Peter Kirwan, Marcella Ma, Giles S. Yeo, Florian T. Merkle, Fiona M. Gribble, Frank Reinmann, Kevin W. Williams, Clémence Blouet","doi":"10.1016/j.cmet.2026.03.017","DOIUrl":"https://doi.org/10.1016/j.cmet.2026.03.017","url":null,"abstract":"Dietary protein promotes satiety and weight loss, yet how appetite-regulating neurons sense dietary protein remains poorly understood. Here, we show that Cacna1g, which encodes the T-type voltage-gated calcium channel Cav3.1, is enriched in hypothalamic leucine-sensing neurons and mediates neuronal leucine sensing. Pharmacological inhibition of Cav3.1 blunts leucine-induced activation of pro-opiomelanocortin (POMC) neurons in cultured neurons and brain slices, thereby suppressing the anorectic response to hypothalamic leucine in vivo. Genetic deletion of Cacna1g in POMC neurons abolishes the appetite- and weight-suppressive effects of high-protein feeding. Mechanistically, leucine binds a hydrophobic pocket of Cav3.1 and lowers its threshold for voltage-dependent activation. Finally, pharmacological activation of mediobasal hypothalamic Cav3.1 promotes weight loss in diet-induced obese mice and potentiates responses to anorectic agents, including liraglutide. Together, these findings establish hypothalamic Cav3.1 as a neuronal leucine sensor and nominate it as a tractable target for anti-obesity therapy.","PeriodicalId":9840,"journal":{"name":"Cell metabolism","volume":"53 1","pages":""},"PeriodicalIF":29.0,"publicationDate":"2026-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147735932","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

A generative AI framework unifies human multi-omics to model aging, metabolic health, and intervention response 生成式人工智能框架将人类多组学结合起来，模拟衰老、代谢健康和干预反应

IF 29 1区生物学

Cell metabolism Pub Date : 2026-04-21 DOI: 10.1016/j.cmet.2026.03.014

Jiawei Chen, Ya Ren, Yong Zhou, Ziyang Wang, Kehang Mao, Zhengqing Yu, Jiyang Li, Xiaoxiao Guo, Hao Xu, Yiyang Wang, Yi Wang, Bo Pang, Hongxiao Liu, Huiru Tang, Jing-Dong J. Han

{"title":"A generative AI framework unifies human multi-omics to model aging, metabolic health, and intervention response","authors":"Jiawei Chen, Ya Ren, Yong Zhou, Ziyang Wang, Kehang Mao, Zhengqing Yu, Jiyang Li, Xiaoxiao Guo, Hao Xu, Yiyang Wang, Yi Wang, Bo Pang, Hongxiao Liu, Huiru Tang, Jing-Dong J. Han","doi":"10.1016/j.cmet.2026.03.014","DOIUrl":"https://doi.org/10.1016/j.cmet.2026.03.014","url":null,"abstract":"Understanding aging and complex diseases requires diverse data, ranging from molecular profiles to imaging and routine clinical tests. However, most multi-omic datasets measure only a subset of modalities and are confounded by batch effects. Here, we present AURORA (AI unification and reconstruction of omics reassembly atlas), a generative deep-learning platform that integrates seven modalities (including transcriptomics, metabolomics, microbiome, 3D and thermal facial imaging, and clinical laboratory tests) across 581,763 samples from 425,258 individuals. AURORA harmonizes batch effects and reconstructs missing data across modalities, enabling highly accurate multimodal aging clocks and disease risk predictors. It also supports personalized <ce:italic>in silico</ce:italic> perturbation analyses to predict intervention and drug responses, validated using longitudinal cohorts. As a proof of concept, we provide a prototype AI agent that converts single-input modalities into a multimodal report for users and researchers. Together, AURORA links non-invasive inputs to comprehensive aging biomarkers and therapeutic discovery.","PeriodicalId":9840,"journal":{"name":"Cell metabolism","volume":"74 1","pages":""},"PeriodicalIF":29.0,"publicationDate":"2026-04-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147752615","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Sensing steroid hormone 17α-hydroxypregnenolone by GPR56 enables protection from ferroptosis-induced liver injury GPR56感知类固醇激素17α-羟基孕烯醇酮对铁中毒引起的肝损伤具有保护作用

IF 29 1区生物学

Cell metabolism Pub Date : 2026-04-20 DOI: 10.1016/j.cmet.2026.04.008

Hui Lin, Chuanshun Ma, Xiao Zhuang, Shuo Liu, Dong Liu, Mingxiang Zhang, Yan Lu, Guangjian Zhou, Chao Zhang, Tengwei Wang, Zihao Zhang, Lin Lv, Daolai Zhang, Xiong-Zhong Ruan, Yunfei Xu, Renjie Chai, Xiao Yu, Jin-Peng Sun, Bo Chu

引用次数: 0

Oxytocin signaling in adipocytes is required for normal milk fat production 脂肪细胞中的催产素信号是正常乳脂生成所必需的

IF 29 1区生物学

Cell metabolism Pub Date : 2026-04-16 DOI: 10.1016/j.cmet.2026.03.013

Erwei Li, Yangmian Yuan, Haijing Sun, Khushi Patel, Nan Zhang, Soumya Nagesh, Juan J. Aristizabal-Henao, Michael Kiebish, Christopher Jacobs, Dave Bridges, Brigid Gregg, Evan D. Rosen

{"title":"Oxytocin signaling in adipocytes is required for normal milk fat production","authors":"Erwei Li, Yangmian Yuan, Haijing Sun, Khushi Patel, Nan Zhang, Soumya Nagesh, Juan J. Aristizabal-Henao, Michael Kiebish, Christopher Jacobs, Dave Bridges, Brigid Gregg, Evan D. Rosen","doi":"10.1016/j.cmet.2026.03.013","DOIUrl":"https://doi.org/10.1016/j.cmet.2026.03.013","url":null,"abstract":"Milk triglycerides, a crucial nutrient source for newborn mammals, can be derived from adipose lipolysis, dietary sources, or de novo synthesis in mammary epithelial cells (MECs). Here, we identify a critical role for the neuropeptide oxytocin (OXT) in providing milk triglyceride needed to sustain neonatal growth, mediated by its actions on adipose lipolysis. Dams lacking OXT receptors (OXTRs) specifically in adipocytes (OxtrΔAd) give birth to pups with reduced weight gain. Oxytocinergic sympathetic neurons are the relevant source of OXT mediating this effect. Milk from OxtrΔAd dams was deficient in triglycerides, which could be rescued by liberalizing dietary fat intake. Finally, single-cell analysis of lactating mammary glands from OxtrΔAd dams revealed a profound shift in the metabolic programming of MECs, indicative of reduced mTOR signaling, increased autophagy, and reduced lipid synthesis. These findings highlight the critical role of OXT-mediated adipose lipolysis in mammalian lactation, demonstrating that lipolysis-derived free fatty acids (FFAs) are essential for normal milk fat and neonatal health.","PeriodicalId":9840,"journal":{"name":"Cell metabolism","volume":"408 1","pages":""},"PeriodicalIF":29.0,"publicationDate":"2026-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147696133","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Mitochondrial metabolism regulates the immunogenic responsiveness of dendritic cells 线粒体代谢调节树突状细胞的免疫原性反应

IF 29 1区生物学

Cell metabolism Pub Date : 2026-04-15 DOI: 10.1016/j.cmet.2026.03.012

Ignacio Heras-Murillo, Diego Mañanes, Josep Calafell-Segura, Adrián Belinchón García, Clara Borràs-Eroles, Pablo Munné, Annalaura Mastrangelo, Sarai Martínez-Cano, Pablo Hernansanz-Agustín, María A. Zuriaga, José J. Fuster, Marten Szibor, Ignacio Melero, José Antonio Enríquez, Navdeep S. Chandel, Esteban Ballestar, Stefanie K. Wculek, David Sancho

{"title":"Mitochondrial metabolism regulates the immunogenic responsiveness of dendritic cells","authors":"Ignacio Heras-Murillo, Diego Mañanes, Josep Calafell-Segura, Adrián Belinchón García, Clara Borràs-Eroles, Pablo Munné, Annalaura Mastrangelo, Sarai Martínez-Cano, Pablo Hernansanz-Agustín, María A. Zuriaga, José J. Fuster, Marten Szibor, Ignacio Melero, José Antonio Enríquez, Navdeep S. Chandel, Esteban Ballestar, Stefanie K. Wculek, David Sancho","doi":"10.1016/j.cmet.2026.03.012","DOIUrl":"https://doi.org/10.1016/j.cmet.2026.03.012","url":null,"abstract":"Activation of conventional dendritic cells (cDCs) favors increased glycolysis-driven lactic fermentation, while oxidative phosphorylation (OXPHOS) links to tolerance. Here, selective targeting of the mitochondrial electron transport chain (ETC) in cDCs uncovers a critical role for OXPHOS in regulating their immunogenicity. Disruption of ETC complex III dampens adjuvant-triggered primary human and mouse cDC1 activation and their capability to prime T cells for anti-cancer immunity, while it has a milder effect on cDC2s. Mechanistically, complex III impairment in cDC1s leads to a dysregulated redox and metabolite balance, altering DNA methylation of PU.1 and activator-protein-1 (AP-1) binding regions. These epigenetic changes hinder the rapid induction of immediate-early stimulus-induced genes in cDC1s upon stimulation. The reduced immunogenic responsiveness of ETC-impaired cDC1s can be rescued by ectopic expression of alternative oxidase and phenocopied by Tet2 deficiency. Our findings reveal that electron flow through the ETC maintains a poised activation state in cDC1s, essential for effective anti-tumor immunity.","PeriodicalId":9840,"journal":{"name":"Cell metabolism","volume":"1 1","pages":""},"PeriodicalIF":29.0,"publicationDate":"2026-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147695502","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

How to train your rodent: Recommendations for the preclinical study of exercise-induced benefits in metabolic research 如何训练你的啮齿动物：代谢研究中运动诱导益处的临床前研究建议

IF 29 1区生物学

Cell metabolism Pub Date : 2026-04-06 DOI: 10.1016/j.cmet.2026.03.005

Steffen H. Raun, Tang Cam Phung Pham, Mark R. Viggars, Satoru Ato, Yuta Takagaki, Zhen Yan, Katrien De Bock, Troy A. Hornberger, Erik A. Richter, Johan Auwerx, Laurie J. Goodyear, Mark A. Febbraio, Karyn A. Esser, Lykke Sylow

{"title":"How to train your rodent: Recommendations for the preclinical study of exercise-induced benefits in metabolic research","authors":"Steffen H. Raun, Tang Cam Phung Pham, Mark R. Viggars, Satoru Ato, Yuta Takagaki, Zhen Yan, Katrien De Bock, Troy A. Hornberger, Erik A. Richter, Johan Auwerx, Laurie J. Goodyear, Mark A. Febbraio, Karyn A. Esser, Lykke Sylow","doi":"10.1016/j.cmet.2026.03.005","DOIUrl":"https://doi.org/10.1016/j.cmet.2026.03.005","url":null,"abstract":"Regular physical activity is fundamental in promoting health and longevity. Numerous studies highlight the beneficial effects of exercise on metabolic parameters, but uncovering the mechanisms underlying the complex cellular responses and adaptations remains challenging in humans. Thus, animal models, in particular rodent models, have been indispensable for unveiling the underlying biological responses to exercise. Studies with precise exercise designs and diverse genetic models are vital for uncovering mechanistic pathways and informing pharmacological and behavioral strategies to combat non-communicable chronic diseases. Despite decades of research, recommendations to design preclinical exercise interventions and to measure key metabolic exercise adaptations in rodents have yet to be established. To enhance animal-to-human translation and ensure reproducibility, exercise studies must be rigorously controlled. Here, we outline key experimental considerations in rodents, including protocol design, exercise modality, sex, age, housing temperature, and circadian rhythm, to guide best practices and promote standardization and translation in future preclinical exercise studies.","PeriodicalId":9840,"journal":{"name":"Cell metabolism","volume":"425 1","pages":""},"PeriodicalIF":29.0,"publicationDate":"2026-04-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147630088","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Body-wide multi-omic counteraction of aging with GLP-1R agonism 衰老与GLP-1R激动作用的全身多基因组对抗

IF 29 1区生物学

Cell metabolism Pub Date : 2026-04-03 DOI: 10.1016/j.cmet.2026.03.016

Junzhe Huang, Andrew J. Kwok, Jason Chak Yan Li, Clement Lek Hin Chiu, Bonaventure Y. Ip, Lok Yi Tung, Roy C.H. Chan, Danny C.W. Chan, Ziyu Wang, Xianyi Zheng, Hoi Tung Chow, Michelle P.S. Lo, Zhongqi Li, Nenghan Lin, Manyu Wang, Leo Y.C. Yan, William K.K. Wu, Kim Hei-Man Chow, Wei-Jye Lin, Yamei Tang, Yun Zhang, Weihong Song, Billy Wai-Lung Ng, Sunny H. Wong, Thomas W. Leung, Vincent C.T. Mok, Ho Ko

引用次数: 0