Cell metabolism最新文献_第2页

Hepatic acetyl-CoA metabolism modulates neuroinflammation and depression susceptibility via acetate 肝脏乙酰辅酶a代谢通过乙酸调节神经炎症和抑郁易感性

IF 29 1区生物学

Cell metabolism Pub Date : 2025-09-23 DOI: 10.1016/j.cmet.2025.08.010

Yu Cao, Yang Zhao, Tan Deng, Qigang Zhou, Gang Hu, Zhuang-Li Hu, Yan-Yi Jiang, Xiao-Han Yang, Fang Wang, Peng-Fei Wu, Jian-Guo Chen

{"title":"Hepatic acetyl-CoA metabolism modulates neuroinflammation and depression susceptibility via acetate","authors":"Yu Cao, Yang Zhao, Tan Deng, Qigang Zhou, Gang Hu, Zhuang-Li Hu, Yan-Yi Jiang, Xiao-Han Yang, Fang Wang, Peng-Fei Wu, Jian-Guo Chen","doi":"10.1016/j.cmet.2025.08.010","DOIUrl":"https://doi.org/10.1016/j.cmet.2025.08.010","url":null,"abstract":"Extensive research highlights impaired brain energy metabolism in neuropsychiatric disorders, whereas much less is known about the role of the peripheral metabolic state. The liver is the metabolic hub, and herein we demonstrate that hepatic hydrolysis of acetyl-coenzyme A, a central metabolic intermediate, signals the brain and helps buffer stress. Using a chronic social defeat stress paradigm in male mice, we observed a hepatic glucose-to-acetate metabolic switch, followed by a glucocorticoid-repressed transcription of the acetyl-coenzyme A hydrolase, acetyl-coenzyme A thioesterase 12, to confer stress vulnerability. Hepatic overexpression of acetyl-coenzyme A thioesterase 12 alleviated depression-like phenotypes via increasing acetate output to promote histone acetylation in the ventral hippocampus, which bolstered the expression of programmed cell death ligand 1 in astrocytes, limiting neuroinflammation and rescuing inhibitory synaptic transmission dysfunction. Our findings demonstrate that hepatic acetyl-coenzyme A hydrolysis serves as a key liver-brain axis component that regulates depression susceptibility.","PeriodicalId":9840,"journal":{"name":"Cell metabolism","volume":"56 1","pages":""},"PeriodicalIF":29.0,"publicationDate":"2025-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145116930","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 closed-loop cholesterol shunt controlling experimental dyslipidemia 控制实验性血脂异常的闭环胆固醇分流

IF 29 1区生物学

Cell metabolism Pub Date : 2025-09-18 DOI: 10.1016/j.cmet.2025.08.011

Gokberk Unal, Yu-Qing Xie, Martin Fussenegger

引用次数: 0

OGFOD1 enables AML chemo- and nutrient stress resistance by regulating protein synthesis OGFOD1通过调节蛋白质合成使AML抵抗化学和营养胁迫

IF 29 1区生物学

Cell metabolism Pub Date : 2025-09-16 DOI: 10.1016/j.cmet.2025.08.008

Christina Mayerhofer, Dan Li, Trine Kristiansen, Ernst Mayerhofer, Azeem Sharda, Giulia Schiroli, Karin Gustafsson, Lingli He, Michael Mazzola, Sam Keyes, Anna Kiem, Eve Crompton, Yanxin Xu, Sovannarith Korm, Zhixun Dou, Charles Vidoudez, Peter G. Miller, Nick van Gastel, Timothy A. Graubert, David T. Scadden

{"title":"OGFOD1 enables AML chemo- and nutrient stress resistance by regulating protein synthesis","authors":"Christina Mayerhofer, Dan Li, Trine Kristiansen, Ernst Mayerhofer, Azeem Sharda, Giulia Schiroli, Karin Gustafsson, Lingli He, Michael Mazzola, Sam Keyes, Anna Kiem, Eve Crompton, Yanxin Xu, Sovannarith Korm, Zhixun Dou, Charles Vidoudez, Peter G. Miller, Nick van Gastel, Timothy A. Graubert, David T. Scadden","doi":"10.1016/j.cmet.2025.08.008","DOIUrl":"https://doi.org/10.1016/j.cmet.2025.08.008","url":null,"abstract":"Acute myeloid leukemia (AML) commonly relapses after initial chemotherapy response. We assessed metabolic adaptations in chemoresistant cells in vivo before overt relapse, identifying altered branched-chain amino acid (BCAA) levels in patient-derived xenografts (PDXs) and immunophenotypically identified leukemia stem cells from AML patients. Notably, this was associated with increased BCAA transporter expression with low BCAA catabolism. Restricting BCAAs further reduced chemoresistant AML cells, but relapse still occurred. Among the persisting cells, we found an unexpected increase in protein production. This was accompanied by elevated translation of 2-oxoglutarate- and iron-dependent oxygenase 1 (OGFOD1), a known ribosomal dioxygenase that adjusts the fidelity of tRNA anticodon pairing with coding mRNA. We found that OGFOD1 upregulates protein synthesis in AML, driving disease aggressiveness. Inhibiting OGFOD1 impaired translation processing, decreased protein synthesis and improved animal survival even with chemoresistant AML while sparing normal hematopoiesis. Leukemic cells can therefore persist despite the stress of chemotherapy and nutrient deprivation through adaptive control of translation. Targeting OGFOD1 may offer a distinctive, translation-modifying means of reducing the chemopersisting cells that drive relapse.","PeriodicalId":9840,"journal":{"name":"Cell metabolism","volume":"15 1","pages":""},"PeriodicalIF":29.0,"publicationDate":"2025-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145067875","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

Portal vein-enriched metabolites as intermediate regulators of the gut microbiome in insulin resistance 门静脉富集代谢物作为胰岛素抵抗中肠道微生物组的中间调节因子

IF 29 1区生物学

Cell metabolism Pub Date : 2025-09-05 DOI: 10.1016/j.cmet.2025.08.005

Vitor Rosetto Muñoz, Francois Moreau, Marion Soto, Yoshiyuki Watanabe, Loc-Duyen Pham, Jimmy Zhong, Sam Zimmerman, Bruna B. Brandao, Khyati Girdhar, Julian Avila, Hui Pan, Jonathan M. Dreyfuss, Michael Y. Mi, Robert E. Gerszten, Emrah Altindis, Aleksandar Kostic, Clary B. Clish, C. Ronald Kahn

{"title":"Portal vein-enriched metabolites as intermediate regulators of the gut microbiome in insulin resistance","authors":"Vitor Rosetto Muñoz, Francois Moreau, Marion Soto, Yoshiyuki Watanabe, Loc-Duyen Pham, Jimmy Zhong, Sam Zimmerman, Bruna B. Brandao, Khyati Girdhar, Julian Avila, Hui Pan, Jonathan M. Dreyfuss, Michael Y. Mi, Robert E. Gerszten, Emrah Altindis, Aleksandar Kostic, Clary B. Clish, C. Ronald Kahn","doi":"10.1016/j.cmet.2025.08.005","DOIUrl":"https://doi.org/10.1016/j.cmet.2025.08.005","url":null,"abstract":"Diet and obesity contribute to insulin resistance and type 2 diabetes, in part via the gut microbiome. To explore the role of gut-derived metabolites in this process, we assessed portal/peripheral blood metabolites in mice with different risks of obesity/diabetes, challenged with a high-fat diet (HFD) + antibiotics. In diabetes/obesity-prone C57BL/6J mice, 111 metabolites were portally enriched and 74 were peripherally enriched, many of which differed in metabolic-syndrome-resistant 129S1/129S6 mice. Vancomycin treatment of HFD-fed C57BL/6J mice modified the microbiome and the portal/peripheral ratio of many metabolites, including upregulating tricarboxylic acid (TCA) cycle-related metabolites, like mesaconate, in portal blood. Treatment of isolated hepatocytes with mesaconate, itaconate, or citraconate improved insulin signaling and transcriptionally regulated genes involved in gluconeogenesis, fatty acid oxidation, and lipogenesis in vitro and in vivo. In humans, citraconate levels are inversely correlated with plasma glucose. Thus, portal versus peripheral metabolites play important roles in mediating effects of the microbiome on hepatic metabolism and the pathogenesis of HFD-related insulin resistance.","PeriodicalId":9840,"journal":{"name":"Cell metabolism","volume":"35 1","pages":""},"PeriodicalIF":29.0,"publicationDate":"2025-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144996037","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

Polycystic ovary syndrome: A metabolic disorder with therapeutic opportunities 多囊卵巢综合征：具有治疗机会的代谢紊乱

IF 29 1区生物学

Cell metabolism Pub Date : 2025-09-04 DOI: 10.1016/j.cmet.2025.08.002

Yuqing Zhang, Zi-Jiang Chen, Han Zhao

引用次数: 0

Mitochondrial dysfunction reveals H2S-mediated synaptic sulfhydration as a potential mechanism for autism-associated social defects 线粒体功能障碍揭示h2s介导的突触巯基化是自闭症相关社会缺陷的潜在机制

IF 29 1区生物学

Cell metabolism Pub Date : 2025-09-03 DOI: 10.1016/j.cmet.2025.08.003

Panpan Xian, Mengmeng Wang, Rougang Xie, Hongyu Ma, Weian Zheng, Junjun Kang, Yujiang Chen, Hanze Liu, Songqi Dong, Haiying Liu, Wenle Zhang, Honghui Mao, Fang Wang, Ning Yang, Jun Yu, Ningxia Zhao, Yazhou Wang, Shengxi Wu

{"title":"Mitochondrial dysfunction reveals H2S-mediated synaptic sulfhydration as a potential mechanism for autism-associated social defects","authors":"Panpan Xian, Mengmeng Wang, Rougang Xie, Hongyu Ma, Weian Zheng, Junjun Kang, Yujiang Chen, Hanze Liu, Songqi Dong, Haiying Liu, Wenle Zhang, Honghui Mao, Fang Wang, Ning Yang, Jun Yu, Ningxia Zhao, Yazhou Wang, Shengxi Wu","doi":"10.1016/j.cmet.2025.08.003","DOIUrl":"https://doi.org/10.1016/j.cmet.2025.08.003","url":null,"abstract":"Clinical studies have identiﬁed multiple mitochondrial disturbances in the peripheral tissues of patients with autism. However, how neuronal metabolism contributes to the autism-associated phenotype remains unclear. In this study, we focused on the anterior cingulate cortex (ACC) and reported hydrogen sulfide (H2S) elevation as a common outcome to mitochondrial dysfunction in Shank3b−/− and Fmr1−/y neurons. Cystathionine β-synthase overexpression in ACC impaired synaptic transmission and social function in wild-type mice, while its knockdown effectively rescued synaptic and social defects in both autism mouse models. Dramatic changes in synaptic protein sulfhydration were observed in Shank3b−/− ACC, with over-sulfhydration of mGluR5 validated in both models. Ablating mGluR5 sulfhydration partially alleviated social deficits in both strains. Furthermore, sulfur amino acid restriction ameliorated social dysfunction in Shank3b−/− and Fmr1−/y mice and synaptic defects in corresponding human neurons. Our data indicate that excessive H2S and synaptic protein sulfhydration may serve as potential mechanisms underlying the autism-associated social dysfunction.","PeriodicalId":9840,"journal":{"name":"Cell metabolism","volume":"29 1","pages":""},"PeriodicalIF":29.0,"publicationDate":"2025-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144930484","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

Reassessment of antibody-based detection of the murine T cell GLP-1 receptor 基于抗体检测小鼠T细胞GLP-1受体的再评估

IF 29 1区生物学

Cell metabolism Pub Date : 2025-09-02 DOI: 10.1016/j.cmet.2025.06.012

Chi Kin Wong, Bernardo Yusta, Jason C.L. Tong, Johannes Broichhagen, David J. Hodson, Daniel J. Drucker

{"title":"Reassessment of antibody-based detection of the murine T cell GLP-1 receptor","authors":"Chi Kin Wong, Bernardo Yusta, Jason C.L. Tong, Johannes Broichhagen, David J. Hodson, Daniel J. Drucker","doi":"10.1016/j.cmet.2025.06.012","DOIUrl":"https://doi.org/10.1016/j.cmet.2025.06.012","url":null,"abstract":"Glucagon-like peptide 1 receptor (GLP-1R) agonists exhibit anti-inflammatory actions, yet the importance of direct immune cell GLP-1R signaling remains uncertain. Although T cells respond to GLP-1, low receptor abundance and suboptimal antisera complicate efforts to characterize immune cell GLP-1R signaling. Here, we evaluate three frequently utilized GLP-1R antibodies, revealing that one of several antibodies, AGR-021, lack ideal specificity for detecting the GLP-1R in mice. Immunostaining with AGR-021 using tissues from two independent GLP-1R knockout mouse lines reveals persistent immunoreactive signals in GLP-1R-null pancreatic islets. Similarly, flow cytometry using AGR-021 reveals no reduction in AGR-021 immunoreactivity in GLP-1R-null splenic T cells. Moreover, western blotting detects AGR-021-immunoreactive proteins from a GLP-1R-negative cell line and fails to detect immunoreactive GLP-1R of the correct size upon overexpression of the receptor. Our findings reveal caveats governing use of multiple widely used GLP-1R antibodies, reemphasizing the importance of rigorous antibody validation for inferring accurate GLP-1R expression.","PeriodicalId":9840,"journal":{"name":"Cell metabolism","volume":"42 1","pages":""},"PeriodicalIF":29.0,"publicationDate":"2025-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144928466","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

NANOG Metabolically Reprograms Tumor-Initiating Stem-like Cells through Tumorigenic Changes in Oxidative Phosphorylation and Fatty Acid Metabolism NANOG通过氧化磷酸化和脂肪酸代谢的致瘤性变化代谢重编程肿瘤启动干细胞

IF 29 1区生物学

Cell metabolism Pub Date : 2025-08-28 DOI: 10.1016/j.cmet.2025.08.007

Chia-Lin Chen, Dinesh Babu Uthaya Kumar, Vasu Punj, Jun Xu, Linda Sher, Stanley M. Tahara, Sonja Hess, Keigo Machida

引用次数: 0

Effect of ultra-processed food consumption on male reproductive and metabolic health 超加工食品消费对男性生殖和代谢健康的影响

IF 29 1区生物学

Cell metabolism Pub Date : 2025-08-28 DOI: 10.1016/j.cmet.2025.08.004

Jessica M. Preston, Jo Iversen, Antonia Hufnagel, Line Hjort, Jodie Taylor, Clara Sanchez, Victoria George, Ann N. Hansen, Lars Ängquist, Susan Hermann, Jeffrey M. Craig, Signe Torekov, Christian Lindh, Karin S. Hougaard, Marcelo A. Nóbrega, Stephen J. Simpson, Romain Barrès

{"title":"Effect of ultra-processed food consumption on male reproductive and metabolic health","authors":"Jessica M. Preston, Jo Iversen, Antonia Hufnagel, Line Hjort, Jodie Taylor, Clara Sanchez, Victoria George, Ann N. Hansen, Lars Ängquist, Susan Hermann, Jeffrey M. Craig, Signe Torekov, Christian Lindh, Karin S. Hougaard, Marcelo A. Nóbrega, Stephen J. Simpson, Romain Barrès","doi":"10.1016/j.cmet.2025.08.004","DOIUrl":"https://doi.org/10.1016/j.cmet.2025.08.004","url":null,"abstract":"Consumption of ultra-processed food is associated with increased caloric intake and impaired health. Here, we conducted a nutrition trial (NCT05368194) with controlled, 2 × 2 crossover design and tested whether ultra-processed food impairs reproductive and metabolic fitness, with further aggravation by excess caloric intake. Comparing the response from an unprocessed to ultra-processed diet identified increased body weight and low-density lipoprotein (LDL):high-density lipoprotein (HDL) ratio, independent of caloric load. Several hormones involved in energy metabolism and spermatogenesis were affected, including decreased levels of growth/differentiation factor 15 and follicle-stimulating hormone. Sperm quality trended toward impairment, with a decrease in total motility. Differential accumulation of pollutants between the discordant diets were detected, such as decreased plasma lithium and a trend for increased levels of the phthalate mono(4-methyl-7-carboxyheptyl)phthalate (cxMINP) in serum, following the ultra-processed diet. Alteration in caloric load alone had distinct effects on the measured outcomes. This study provides evidence that consumption of ultra-processed food is detrimental for cardiometabolic and reproductive outcomes, regardless of excessive caloric intake.","PeriodicalId":9840,"journal":{"name":"Cell metabolism","volume":"28 1","pages":""},"PeriodicalIF":29.0,"publicationDate":"2025-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144911214","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

Homocysitaconate controls inflammation through reshaping methionine metabolism and N-homocysteinylation 同型半胱甘酸盐通过重塑蛋氨酸代谢和n -同型半胱氨酸化来控制炎症

IF 29 1区生物学

Cell metabolism Pub Date : 2025-08-27 DOI: 10.1016/j.cmet.2025.08.001

Moubin Lin, Juan Wang, Yongshuai Chai, Xin Chen, Danyang Zhao, Zhangdan Xie, Jiebang Jiang, Hong Li, Li Huang, Siwei Xing, Dashi Qi, Xinyu Mei

{"title":"Homocysitaconate controls inflammation through reshaping methionine metabolism and N-homocysteinylation","authors":"Moubin Lin, Juan Wang, Yongshuai Chai, Xin Chen, Danyang Zhao, Zhangdan Xie, Jiebang Jiang, Hong Li, Li Huang, Siwei Xing, Dashi Qi, Xinyu Mei","doi":"10.1016/j.cmet.2025.08.001","DOIUrl":"https://doi.org/10.1016/j.cmet.2025.08.001","url":null,"abstract":"Inflammation and its metabolic-network interactions generate novel regulatory molecules with translational implications. Here, we identify the immunometabolic crosstalk that generates homocysitaconate, a metabolite formed by homocysteine and itaconate adduction catalyzed by S-adenosyl-L-homocysteine hydrolase (AHCY). Homocysitaconate increases 152-fold during inflammation and exhibits anti-inflammatory effects. Mechanistically, homocysitaconate binds to the D312 residue of the pro-inflammatory protein methionyl-tRNA synthetase (MARS), inhibiting its function and reshaping methionine metabolism to feedback-brake the early activation of the N-homocysteinylation pathway. This metabolic switch facilitates NLR family pyrin domain-containing 3 (NLRP3) ubiquitination to control inflammation. Homocysitaconate demonstrates therapeutic effects in sepsis, high-fat-diet-induced inflammation, and colitis models. Boosting endogenous homocysitaconate synthesis through nicotinamide adenine dinucleotide (NAD+)-dependent AHCY activation (using nicotinamide riboside and pyruvate) also inhibits inflammation by targeting the MARS/NLRP3-N-homocysteinylation cascade. This study establishes homocysitaconate as an anti-inflammatory metabolite that serves as a homeostatic governor by reprogramming protein modification switches, introducing both metabolic timing regulation and clinical strategies to manage inflammatory complications.","PeriodicalId":9840,"journal":{"name":"Cell metabolism","volume":"24 1","pages":""},"PeriodicalIF":29.0,"publicationDate":"2025-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144906071","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