Cell metabolism最新文献_第2页

FGF21 promotes longevity in diet-induced obesity through metabolic benefits independent of growth suppression FGF21通过独立于生长抑制的代谢益处促进饮食引起的肥胖的寿命

IF 29 1区生物学

Cell metabolism Pub Date : 2025-06-16 DOI: 10.1016/j.cmet.2025.05.011

Christy M. Gliniak, Ruth Gordillo, Yun-Hee Youm, Qian Lin, Clair Crewe, Zhuzhen Zhang, Bianca C. Field, Teppei Fujikawa, Megan Virostek, Shangang Zhao, Yi Zhu, Clifford J. Rosen, Tamas L. Horvath, Vishwa Deep Dixit, Philipp E. Scherer

{"title":"FGF21 promotes longevity in diet-induced obesity through metabolic benefits independent of growth suppression","authors":"Christy M. Gliniak, Ruth Gordillo, Yun-Hee Youm, Qian Lin, Clair Crewe, Zhuzhen Zhang, Bianca C. Field, Teppei Fujikawa, Megan Virostek, Shangang Zhao, Yi Zhu, Clifford J. Rosen, Tamas L. Horvath, Vishwa Deep Dixit, Philipp E. Scherer","doi":"10.1016/j.cmet.2025.05.011","DOIUrl":"https://doi.org/10.1016/j.cmet.2025.05.011","url":null,"abstract":"Approximately 35% of US adults over 65 are obese, highlighting the need for therapies targeting age-related metabolic issues. Fibroblast growth factor 21 (FGF21), a hormone mainly produced by the liver, improves metabolism and extends lifespan. To explore its effects without developmental confounders, we generated mice with adipocyte-specific FGF21 overexpression beginning in adulthood. When fed a high-fat diet, these mice lived up to 3.3 years, resisted weight gain, improved insulin sensitivity, and showed reduced liver steatosis. Aged transgenic mice also displayed lower levels of inflammatory immune cells and lipotoxic ceramides in visceral adipose tissue, benefits that occurred even in the absence of adiponectin, a hormone known to regulate ceramide breakdown. These results suggest that fat tissue is a central site for FGF21’s beneficial effects and point to its potential for treating metabolic syndrome and age-related diseases by promoting a healthier metabolic profile under dietary stress and extending healthspan and lifespan.","PeriodicalId":9840,"journal":{"name":"Cell metabolism","volume":"13 1","pages":""},"PeriodicalIF":29.0,"publicationDate":"2025-06-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144296296","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

Itaconate promotes inflammatory responses in tissue-resident alveolar macrophages and exacerbates acute lung injury 衣康酸促进组织内肺泡巨噬细胞的炎症反应，加重急性肺损伤

IF 29 1区生物学

Cell metabolism Pub Date : 2025-06-16 DOI: 10.1016/j.cmet.2025.05.012

Mengtian Shan, Song Zhang, Zhibing Luo, Shengjie Deng, Linyu Ran, Quan Zhou, Huimin Wan, Jihui Ye, Chenchen Qian, Ximin Fan, Yun Feng, David W. Morse, Joerg Herrmann, Qiang Li, Zhongliang Guo, Feilong Wang

{"title":"Itaconate promotes inflammatory responses in tissue-resident alveolar macrophages and exacerbates acute lung injury","authors":"Mengtian Shan, Song Zhang, Zhibing Luo, Shengjie Deng, Linyu Ran, Quan Zhou, Huimin Wan, Jihui Ye, Chenchen Qian, Ximin Fan, Yun Feng, David W. Morse, Joerg Herrmann, Qiang Li, Zhongliang Guo, Feilong Wang","doi":"10.1016/j.cmet.2025.05.012","DOIUrl":"https://doi.org/10.1016/j.cmet.2025.05.012","url":null,"abstract":"Itaconate is an anti-inflammatory metabolite with therapeutic potential in multiple inflammatory diseases. However, its immunomodulatory function has been mainly based on ex vivo-generated macrophages or cell lines, whereas its role in tissue-resident macrophages is still poorly understood. Here, we report that, in contrast to its effects on bone-marrow-derived macrophages (BMDMs), itaconate promotes the production of proinflammatory cytokines and augments the activation of the NACHT-, leucine-rich-repeat- (LRR), and pyrin domain-containing protein 3 (NLRP3) inflammasome in resident alveolar macrophages (AMs). Unlike native itaconate, the itaconate derivatives dimethyl itaconate (DI) and 4-octyl itaconate (4OI) suppress the inflammatory response in AMs. Notably, the intratracheal transfer of BMDMs reversed their responsiveness to itaconate, indicating an essential role of the alveolar microenvironment in shaping macrophage immunometabolism. We also demonstrate that itaconate promotes AM-mediated inflammatory responses in vivo and aggravates lung injury. Taken together, our study unexpectedly demonstrates a proinflammatory role of itaconate in tissue-resident AMs, suggesting that further investigations are needed before its clinical application.","PeriodicalId":9840,"journal":{"name":"Cell metabolism","volume":"10 1","pages":""},"PeriodicalIF":29.0,"publicationDate":"2025-06-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144296297","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

The integrated stress response fine-tunes stem cell fate decisions upon serine deprivation and tissue injury 综合应激反应微调了丝氨酸剥夺和组织损伤后干细胞命运的决定

IF 29 1区生物学

Cell metabolism Pub Date : 2025-06-12 DOI: 10.1016/j.cmet.2025.05.010

Jesse S.S. Novak, Lisa Polak, Sanjeethan C. Baksh, Douglas W. Barrows, Marina Schernthanner, Benjamin T. Jackson, Elizabeth A.N. Thompson, Anita Gola, M. Deniz Abdusselamoglu, Alain R. Bonny, Kevin A.U. Gonzales, Julia S. Brunner, Anna E. Bridgeman, Katie S. Stewart, Lynette Hidalgo, June Dela Cruz-Racelis, Ji-Dung Luo, Shiri Gur-Cohen, H. Amalia Pasolli, Thomas S. Carroll, Elaine Fuchs

{"title":"The integrated stress response fine-tunes stem cell fate decisions upon serine deprivation and tissue injury","authors":"Jesse S.S. Novak, Lisa Polak, Sanjeethan C. Baksh, Douglas W. Barrows, Marina Schernthanner, Benjamin T. Jackson, Elizabeth A.N. Thompson, Anita Gola, M. Deniz Abdusselamoglu, Alain R. Bonny, Kevin A.U. Gonzales, Julia S. Brunner, Anna E. Bridgeman, Katie S. Stewart, Lynette Hidalgo, June Dela Cruz-Racelis, Ji-Dung Luo, Shiri Gur-Cohen, H. Amalia Pasolli, Thomas S. Carroll, Elaine Fuchs","doi":"10.1016/j.cmet.2025.05.010","DOIUrl":"https://doi.org/10.1016/j.cmet.2025.05.010","url":null,"abstract":"Epidermal stem cells produce the skin’s barrier that excludes pathogens and prevents dehydration. Hair follicle stem cells (HFSCs) are dedicated to bursts of hair regeneration, but upon injury, they can also reconstruct, and thereafter maintain, the overlying epidermis. How HFSCs balance these fate choices to restore physiologic function to damaged tissue remains poorly understood. Here, we uncover serine as an unconventional, non-essential amino acid that impacts this process. When dietary serine dips, endogenous biosynthesis in HFSCs fails to meet demands (and vice versa), slowing hair cycle entry. Serine deprivation also alters wound repair, further delaying hair regeneration while accelerating re-epithelialization kinetics. Mechanistically, we show that HFSCs sense each fitness challenge by triggering the integrated stress response, which acts as a rheostat of epidermal-HF identity. As stress levels rise, skin barrier restoration kinetics accelerate while hair growth is delayed. Our findings offer potential for dietary and pharmacological intervention to accelerate wound healing.","PeriodicalId":9840,"journal":{"name":"Cell metabolism","volume":"589 1","pages":""},"PeriodicalIF":29.0,"publicationDate":"2025-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144269254","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

Derepressing nuclear pyruvate dehydrogenase induces therapeutic cancer cell reprogramming 抑制核丙酮酸脱氢酶诱导治疗性癌细胞重编程

IF 29 1区生物学

Cell metabolism Pub Date : 2025-06-11 DOI: 10.1016/j.cmet.2025.05.009

Ting Zhao, Lingli He, Lai Ping Wong, Shenglin Mei, Jun Xia, Yanxin Xu, Jonathan G. Van Vranken, Michael Mazzola, Lei Chen, Catherine Rhee, Tiancheng Fang, Tsuyoshi Fukushima, Leanne C. Sayles, Matthew Diaz, J. Alex B. Gibbons, Raul Mostoslavsky, Steven P. Gygi, Zhixun Dou, David B. Sykes, Ruslan I. Sadreyev, David T. Scadden

{"title":"Derepressing nuclear pyruvate dehydrogenase induces therapeutic cancer cell reprogramming","authors":"Ting Zhao, Lingli He, Lai Ping Wong, Shenglin Mei, Jun Xia, Yanxin Xu, Jonathan G. Van Vranken, Michael Mazzola, Lei Chen, Catherine Rhee, Tiancheng Fang, Tsuyoshi Fukushima, Leanne C. Sayles, Matthew Diaz, J. Alex B. Gibbons, Raul Mostoslavsky, Steven P. Gygi, Zhixun Dou, David B. Sykes, Ruslan I. Sadreyev, David T. Scadden","doi":"10.1016/j.cmet.2025.05.009","DOIUrl":"https://doi.org/10.1016/j.cmet.2025.05.009","url":null,"abstract":"Metabolites are essential substrates for epigenetic modifications. Although nuclear acetyl-coenzyme A (CoA) constitutes a small fraction of the whole-cell pool, it regulates cell fate by locally providing histone acetylation substrate. Here, we report a nucleus-specific acetyl-CoA regulatory mechanism that can be modulated to achieve therapeutic cancer cell reprogramming. Combining phenotypic chemical screen, genome-wide CRISPR screen, and proteomics, we identified that the nucleus-localized pyruvate dehydrogenase complex (nPDC) is constitutively inhibited by the nuclear protein ELMSAN1 through direct interaction. Pharmacologic inhibition of the ELMSAN1-nPDC interaction derepressed nPDC activity, enhancing nuclear acetyl-CoA generation and reprogramming cancer cells to a postmitotic state with diminished cell-of-origin signatures. Reprogramming was synergistically enhanced by histone deacetylase 1/2 inhibition, resulting in inhibited tumor growth, durably suppressed tumor-initiating ability, and improved survival in multiple cancer types in vivo, including therapy-resistant sarcoma patient-derived xenografts and carcinoma cell line xenografts. Our findings highlight the potential of targeting ELMSAN1-nPDC as an epigenetic cancer therapy.","PeriodicalId":9840,"journal":{"name":"Cell metabolism","volume":"21 1","pages":""},"PeriodicalIF":29.0,"publicationDate":"2025-06-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144260300","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

Genetic and physiological insights into satiation variability predict responses to obesity treatment 从遗传学和生理学角度了解饱足变异性，预测对肥胖治疗的反应

IF 29 1区生物学

Cell metabolism Pub Date : 2025-06-06 DOI: 10.1016/j.cmet.2025.05.008

Lizeth Cifuentes, Diego Anazco, Timothy O’Connor, Maria Daniela Hurtado, Wissam Ghusn, Alejandro Campos, Sima Fansa, Alison McRae, Sunil Madhusudhan, Elle Kolkin, Michael Ryks, William S. Harmsen, Serban Ciotlos, Barham K. Abu Dayyeh, Donald D. Hensrud, Michael Camilleri, Andres Acosta

{"title":"Genetic and physiological insights into satiation variability predict responses to obesity treatment","authors":"Lizeth Cifuentes, Diego Anazco, Timothy O’Connor, Maria Daniela Hurtado, Wissam Ghusn, Alejandro Campos, Sima Fansa, Alison McRae, Sunil Madhusudhan, Elle Kolkin, Michael Ryks, William S. Harmsen, Serban Ciotlos, Barham K. Abu Dayyeh, Donald D. Hensrud, Michael Camilleri, Andres Acosta","doi":"10.1016/j.cmet.2025.05.008","DOIUrl":"https://doi.org/10.1016/j.cmet.2025.05.008","url":null,"abstract":"Satiation, the process that regulates meal size and termination, varies widely among adults with obesity. To better understand and leverage this variability, we assessed calories to satiation (CTS) through an ad libitum meal, combined with physiological and behavioral evaluations, including calorimetry, imaging, blood sampling, and gastric emptying tests. Although factors like baseline characteristics, body composition, and hormone levels partially explain CTS variability, they leave substantial variability unaccounted for. To address this gap, we developed a machine-learning-assisted genetic risk score (CTSGRS) to predict high CTS. In a randomized clinical trial, participants with high CTS or CTSGRS achieved greater weight loss with phentermine-topiramate over 52 weeks, whereas those with low CTS or CTSGRS responded better to liraglutide at 16 weeks in a separate trial. These findings highlight the potential of combining satiation measurements with genetic modeling to predict treatment outcomes and inform personalized strategies for obesity management.","PeriodicalId":9840,"journal":{"name":"Cell metabolism","volume":"60 1","pages":""},"PeriodicalIF":29.0,"publicationDate":"2025-06-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144228676","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

Metabolic switches in cell death regulation 细胞死亡调控中的代谢开关

IF 29 1区生物学

Cell metabolism Pub Date : 2025-06-03 DOI: 10.1016/j.cmet.2025.04.017

Lorenzo Galluzzi

引用次数: 0

Cell Metabolism 20th anniversary Voices: Part 3 of 3 细胞代谢20周年纪念声音：三集之三

IF 29 1区生物学

Cell metabolism Pub Date : 2025-06-03 DOI: 10.1016/j.cmet.2025.05.006

Matthew Potthoff, Rana K. Gupta, Changhan Lee, Jonathan Z. Long, Jonathan R. Brestoff, Katrien de Bock

引用次数: 0

Testing the carbohydrate-insulin model: Some aspects are consistent, but overall the data do not support the model 测试碳水化合物-胰岛素模型：某些方面是一致的，但总体数据不支持模型