Cell metabolismPub Date : 2026-04-22DOI: 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
{"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.2026.04.010","DOIUrl":"https://doi.org/10.1016/j.cmet.2026.04.010","url":null,"abstract":"(Cell Metabolism <em>38</em>, ◼◼◼–◼◼◼; May 5, 2026)","PeriodicalId":9840,"journal":{"name":"Cell metabolism","volume":"21 1","pages":""},"PeriodicalIF":29.0,"publicationDate":"2026-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147744081","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}
Cell metabolismPub Date : 2026-04-22DOI: 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 <em>Cacna1g</em>, 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 <em>in vivo</em>. Genetic deletion of <em>Cacna1g</em> 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}
Cell metabolismPub Date : 2026-04-21DOI: 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}
Cell metabolismPub Date : 2026-04-16DOI: 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 <em>de novo</em> 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 (<em>Oxtr</em><sup>ΔAd</sup>) give birth to pups with reduced weight gain. Oxytocinergic sympathetic neurons are the relevant source of OXT mediating this effect. Milk from <em>Oxtr</em><sup>ΔAd</sup> dams was deficient in triglycerides, which could be rescued by liberalizing dietary fat intake. Finally, single-cell analysis of lactating mammary glands from <em>Oxtr</em><sup>ΔAd</sup> 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}
Cell metabolismPub Date : 2026-04-15DOI: 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 <em>Tet2</em> 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}
Cell metabolismPub Date : 2026-04-06DOI: 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}
Cell metabolismPub Date : 2026-04-03DOI: 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
{"title":"Body-wide multi-omic counteraction of aging with GLP-1R agonism","authors":"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","doi":"10.1016/j.cmet.2026.03.016","DOIUrl":"https://doi.org/10.1016/j.cmet.2026.03.016","url":null,"abstract":"","PeriodicalId":9840,"journal":{"name":"Cell metabolism","volume":"3 1","pages":""},"PeriodicalIF":29.0,"publicationDate":"2026-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147598166","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}
Cell metabolismPub Date : 2026-04-01DOI: 10.1016/j.cmet.2026.03.018
Thomas Marjot, Kieran Smith, Felix Westcott, Sarah White, Elspeth Johnson, Nikola Srnic, Amy Barrett, Ellis Hall, Kate Gralton, Kaitlyn Dennis, Hamish Miller, Riccardo Pofi, Jeremy F.L. Cobbold, Rebecca Richmond, Fredrik Karpe, Ronnie Blazev, Matthew J. Watt, Benjamin L. Parker, Leanne Hodson, David W. Ray, Jeremy W. Tomlinson
{"title":"Human MASLD is a diurnal disease driven by multisystem insulin resistance and reduced insulin availability at night","authors":"Thomas Marjot, Kieran Smith, Felix Westcott, Sarah White, Elspeth Johnson, Nikola Srnic, Amy Barrett, Ellis Hall, Kate Gralton, Kaitlyn Dennis, Hamish Miller, Riccardo Pofi, Jeremy F.L. Cobbold, Rebecca Richmond, Fredrik Karpe, Ronnie Blazev, Matthew J. Watt, Benjamin L. Parker, Leanne Hodson, David W. Ray, Jeremy W. Tomlinson","doi":"10.1016/j.cmet.2026.03.018","DOIUrl":"https://doi.org/10.1016/j.cmet.2026.03.018","url":null,"abstract":"(Cell Metabolism <em>38</em>, 474–492.e1–e6; March 3, 2026)","PeriodicalId":9840,"journal":{"name":"Cell metabolism","volume":"61 1","pages":""},"PeriodicalIF":29.0,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147586416","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}
Cell metabolismPub Date : 2026-04-01DOI: 10.1016/j.cmet.2026.03.003
Ting-Ting Wang, Yan-Jia Luo, Wen Feng, Lian-Xiang Jiang, Qing-Song Yu, Yu-Ting He, Lizhi Guan, Bing-Qian Zhu, Hong Jiang, Min Li, Ruixin Liu, Jing Wang, Ya-Dong Li
{"title":"Gut microbial metabolism via hippocampal indole-AhR signaling regulates emotional symptoms","authors":"Ting-Ting Wang, Yan-Jia Luo, Wen Feng, Lian-Xiang Jiang, Qing-Song Yu, Yu-Ting He, Lizhi Guan, Bing-Qian Zhu, Hong Jiang, Min Li, Ruixin Liu, Jing Wang, Ya-Dong Li","doi":"10.1016/j.cmet.2026.03.003","DOIUrl":"https://doi.org/10.1016/j.cmet.2026.03.003","url":null,"abstract":"Gut microbiota modulate emotion, yet mechanistic insight and therapeutic targets remain limited. Here, we identify reduced gut microbiota-derived indole causally modulating emotion through hippocampal aryl hydrocarbon receptor (AhR). We found that decreased abundance of <em>Alistipes shahii</em> reduced intestinal indole levels via loss of tryptophanase, the rate-limiting step for indole production in microbial tryptophan metabolism, in irritable bowel syndrome (IBS) patients and model mice. In the brain, indole acts via AhR, which is enriched in the ventral dentate gyrus (vDG), a hub in regulating emotion. Reduced indole diminished nuclear AhR expression and vDG granule cell activity, leading to affective symptoms. Tryptophanase-producing microbiota transplantation, indole/tryptophanase supplementation, chemogenetic activation of vDG neurons, or diosmin, a clinically approved AhR agonist, rescued emotional symptoms in IBS mice. Together, these findings define an <em>Alistipes shahii</em>-tryptophanase-indole-AhR-vDG pathway as a mechanistic and translationally tractable gut-brain axis underlying affective disturbances.","PeriodicalId":9840,"journal":{"name":"Cell metabolism","volume":"12 1","pages":""},"PeriodicalIF":29.0,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147586726","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}
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