Cell metabolismPub Date : 2025-05-06DOI: 10.1016/j.cmet.2025.04.004
Shingo Kajimura, Cristina García-Cáceres, Lawrence Kazak, Edward B. Thorp, Katrin J. Svensson, Ling Yang
{"title":"Cell Metabolism 20th anniversary Voices: Part 2 of 3","authors":"Shingo Kajimura, Cristina García-Cáceres, Lawrence Kazak, Edward B. Thorp, Katrin J. Svensson, Ling Yang","doi":"10.1016/j.cmet.2025.04.004","DOIUrl":"https://doi.org/10.1016/j.cmet.2025.04.004","url":null,"abstract":"This year, <em>Cell Metabolism</em> is celebrating its 20th anniversary! We are taking this opportunity to highlight authors that have published with us as they developed, and keep developing, their research careers. In 2005, <em>Cell Metabolism</em> was just starting an exciting journey to become a reference forum for interdisciplinary, high-quality metabolism studies. Throughout these years, it has been an honor to feature in our issues articles from these investigators and their labs that have contributed to both consolidating and expanding the metabolism field.","PeriodicalId":9840,"journal":{"name":"Cell metabolism","volume":"139 1","pages":""},"PeriodicalIF":29.0,"publicationDate":"2025-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143910701","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 : 2025-05-06DOI: 10.1016/j.cmet.2025.04.003
M. Yanina Pepino, Jaume Amengual
{"title":"Does sweet turn sour? How aspartame aggravates atherosclerosis in a preclinical model","authors":"M. Yanina Pepino, Jaume Amengual","doi":"10.1016/j.cmet.2025.04.003","DOIUrl":"https://doi.org/10.1016/j.cmet.2025.04.003","url":null,"abstract":"Aspartame, a low-calorie sweetener (LCS), was shown to be safe through extensive pre-clinical and clinical tests. However, epidemiological data link aspartame and other LCSs to higher cardiovascular risk. In this issue of <em>Cell Metabolism</em>, Wu et al.<span><span><sup>1</sup></span></span> show that aspartame accelerates atherosclerosis via a vagal-mediated insulin-dependent mechanism in a hyperlipidemic mouse model.","PeriodicalId":9840,"journal":{"name":"Cell metabolism","volume":"39 1","pages":""},"PeriodicalIF":29.0,"publicationDate":"2025-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143910616","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 : 2025-05-06DOI: 10.1016/j.cmet.2025.03.018
Andrea Riviello, Dirk Brenner
{"title":"Bacteria-derived nutrient recycling: How phagocytosed bacteria regulate macrophage metabolism","authors":"Andrea Riviello, Dirk Brenner","doi":"10.1016/j.cmet.2025.03.018","DOIUrl":"https://doi.org/10.1016/j.cmet.2025.03.018","url":null,"abstract":"Macrophages are responsible for sensing, phagocytosing, and destroying bacteria, yet the metabolic fate of these internalized microbes remains largely unexplored. A recent study published by Lesbats et al. in <em>Nature</em><span><span><sup>1</sup></span></span> uncovers how macrophages recycle some of the components from phagolysosomal degradation, using them as intermediates in various anabolic pathways and as fuel for oxidative phosphorylation.","PeriodicalId":9840,"journal":{"name":"Cell metabolism","volume":"24 1","pages":""},"PeriodicalIF":29.0,"publicationDate":"2025-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143910691","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}
{"title":"Foxp3 confers long-term efficacy of chimeric antigen receptor-T cells via metabolic reprogramming","authors":"Congyi Niu, Huan Wei, Xuanxuan Pan, Yuedi Wang, Huan Song, Congwen Li, Jingbo Qie, Jiawen Qian, Shaocong Mo, Wanwei Zheng, Kameina Zhuma, Zixin Lv, Yiyuan Gao, Dan Zhang, Hui Yang, Ronghua Liu, Luman Wang, Wenwei Tu, Jie Liu, Yiwei Chu, Feifei Luo","doi":"10.1016/j.cmet.2025.04.008","DOIUrl":"https://doi.org/10.1016/j.cmet.2025.04.008","url":null,"abstract":"The tumor microenvironment, characterized by low oxygen tension and scarce nutrients, impairs chimeric antigen receptor (CAR)-T cell metabolism, leading to T cell exhaustion and dysfunction. Notably, Foxp3 confers a metabolic advantage to regulatory T cells under such restrictive conditions. Exploiting this property, we generated CAR-T<sub>Foxp3</sub> cells by co-expressing Foxp3 with a third-generation CAR construct. The CAR-T<sub>Foxp3</sub> cells exhibited distinct metabolic reprogramming, marked by downregulated aerobic glycolysis and oxidative phosphorylation coupled with upregulated lipid metabolism. This metabolic shift was driven by Foxp3’s interaction with dynamin-related protein 1. Crucially, CAR-T<sub>Foxp3</sub> cells did not acquire regulatory T cell immunosuppressive functions but instead demonstrated enhanced antitumor potency and reduced expression of exhaustion markers via Foxp3-mediated adaptation. The potent antitumor effect and absence of immunosuppression were confirmed in a humanized immune system mouse model. Our findings establish a metabolic reprogramming-based strategy to enhance CAR-T cell adaptability within the hostile tumor microenvironment while preserving therapeutic efficacy.","PeriodicalId":9840,"journal":{"name":"Cell metabolism","volume":"17 1","pages":""},"PeriodicalIF":29.0,"publicationDate":"2025-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143905435","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}
{"title":"Fasting-induced ketogenesis sensitizes bacteria to antibiotic treatment","authors":"Shujun Cui, Danyang Chong, Yi-Xin Wang, Huixian Tong, Minggui Wang, Guo-Ping Zhao, Liang-Dong Lyu","doi":"10.1016/j.cmet.2025.04.006","DOIUrl":"https://doi.org/10.1016/j.cmet.2025.04.006","url":null,"abstract":"Fasting metabolism is a commonly observed motivational response to acute infections and is conceptualized as being beneficial for host survival. Here, we show that fasting potentiates antibiotic treatment for murine sepsis caused by <em>Salmonella</em> Typhimurium, <em>Klebsiella pneumoniae</em>, and <em>Enterobacter cloacae</em>, resulting in increased bacterial clearance and improved host immune responses and survival. This effect is mediated by fasting-induced ketogenesis and could be alternatively implemented by combination therapy with antibiotics and ketone bodies. We show that the ketone body acetoacetate is an effector that sensitizes bacteria to antibiotic treatment by increasing antibiotic lethality and outer and inner membrane permeability. Our results demonstrate that acetoacetate depletes bacterial amino acids, particularly positively charged amino acids and putrescine, leading to cell membrane malfunctions and redox-related lethality. This study reveals an unrecognized role of ketogenesis in antibiotic treatment and a potential ketone body-based treatment strategy for bacterial sepsis.","PeriodicalId":9840,"journal":{"name":"Cell metabolism","volume":"24 1","pages":""},"PeriodicalIF":29.0,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143893223","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 : 2025-05-01DOI: 10.1016/j.cmet.2025.04.007
Won-Suk Song, Xiyu Shen, Kang Du, Cuauhtemoc B. Ramirez, Sang Hee Park, Yang Cao, Johnny Le, Hosung Bae, Joohwan Kim, Yujin Chun, Nikki Joyce Khong, Marie Kim, Sunhee Jung, Wonsuk Choi, Miranda L. Lopez, Zaid Said, Zehan Song, Sang-Guk Lee, Dequina Nicholas, Yo Sasaki, Qin Yang
{"title":"Nicotinic acid riboside maintains NAD+ homeostasis and ameliorates aging-associated NAD+ decline","authors":"Won-Suk Song, Xiyu Shen, Kang Du, Cuauhtemoc B. Ramirez, Sang Hee Park, Yang Cao, Johnny Le, Hosung Bae, Joohwan Kim, Yujin Chun, Nikki Joyce Khong, Marie Kim, Sunhee Jung, Wonsuk Choi, Miranda L. Lopez, Zaid Said, Zehan Song, Sang-Guk Lee, Dequina Nicholas, Yo Sasaki, Qin Yang","doi":"10.1016/j.cmet.2025.04.007","DOIUrl":"https://doi.org/10.1016/j.cmet.2025.04.007","url":null,"abstract":"Liver-derived circulating nicotinamide from nicotinamide adenine dinucleotide (NAD<sup>+</sup>) catabolism primarily feeds systemic organs for NAD<sup>+</sup> synthesis. We surprisingly found that, despite blunted hepatic NAD<sup>+</sup> and nicotinamide production in liver-specific nicotinamide nucleotide adenylyltransferase 1 (NMNAT1) deletion mice (liver-specific knockout [LKO]), circulating nicotinamide and extra-hepatic organs’ NAD<sup>+</sup> are unaffected. Metabolomics reveals a massive accumulation of a novel molecule in the LKO liver, which we identify as nicotinic acid riboside (NaR). We further demonstrate cytosolic 5′-nucleotidase II (NT5C2) as the NaR-producing enzyme. The liver releases NaR to the bloodstream, and kidneys take up NaR to synthesize NAD<sup>+</sup> through nicotinamide riboside kinase 1 (NRK1) and replenish circulating nicotinamide. Serum NaR levels decline with aging, whereas oral NaR supplementation in aged mice boosts serum nicotinamide and multi-organ NAD<sup>+</sup>, including kidneys, and reduces kidney inflammation and albuminuria. Thus, the liver-kidney axis maintains systemic NAD<sup>+</sup> homeostasis via circulating NaR, and NaR supplement ameliorates aging-associated NAD<sup>+</sup> decline and kidney dysfunction.","PeriodicalId":9840,"journal":{"name":"Cell metabolism","volume":"91 1","pages":""},"PeriodicalIF":29.0,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143893224","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 : 2025-04-30DOI: 10.1016/j.cmet.2025.04.002
Sabina Chubanava, Iuliia Karavaeva, Amy M. Ehrlich, Roger M. Justicia, Astrid L. Basse, Ivan Kulik, Emilie Dalbram, Danial Ahwazi, Samuel R. Heaselgrave, Kajetan Trošt, Ben Stocks, Ondřej Hodek, Raissa N. Rodrigues, Jesper F. Havelund, Farina L. Schlabs, Steen Larsen, Caio Y. Yonamine, Carlos Henriquez-Olguín, Daniela Giustarini, Ranieri Rossi, Jonas T. Treebak
{"title":"NAD depletion in skeletal muscle does not compromise muscle function or accelerate aging","authors":"Sabina Chubanava, Iuliia Karavaeva, Amy M. Ehrlich, Roger M. Justicia, Astrid L. Basse, Ivan Kulik, Emilie Dalbram, Danial Ahwazi, Samuel R. Heaselgrave, Kajetan Trošt, Ben Stocks, Ondřej Hodek, Raissa N. Rodrigues, Jesper F. Havelund, Farina L. Schlabs, Steen Larsen, Caio Y. Yonamine, Carlos Henriquez-Olguín, Daniela Giustarini, Ranieri Rossi, Jonas T. Treebak","doi":"10.1016/j.cmet.2025.04.002","DOIUrl":"https://doi.org/10.1016/j.cmet.2025.04.002","url":null,"abstract":"Nicotinamide adenine dinucleotide (NAD) is a ubiquitous electron carrier essential for energy metabolism and post-translational modification of numerous regulatory proteins. Dysregulations of NAD metabolism are widely regarded as detrimental to health, with NAD depletion commonly implicated in aging. However, the extent to which cellular NAD concentration can decline without adverse consequences remains unclear. To investigate this, we generated a mouse model in which nicotinamide phosphoribosyltransferase (NAMPT)-mediated NAD<sup>+</sup> biosynthesis was disrupted in adult skeletal muscle. The intervention resulted in an 85% reduction in muscle NAD<sup>+</sup> abundance while maintaining tissue integrity and functionality, as demonstrated by preserved muscle morphology, contractility, and exercise tolerance. This absence of functional impairments was further supported by intact mitochondrial respiratory capacity and unaltered muscle transcriptomic and proteomic profiles. Furthermore, lifelong NAD depletion did not accelerate muscle aging or impair whole-body metabolism. Collectively, these findings suggest that NAD depletion does not contribute to age-related decline in skeletal muscle function.","PeriodicalId":9840,"journal":{"name":"Cell metabolism","volume":"105 1","pages":""},"PeriodicalIF":29.0,"publicationDate":"2025-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143889985","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 : 2025-04-29DOI: 10.1016/j.cmet.2025.04.012
Ying Liu, Huihui Mei, Li Xue, Chuanli Cheng, Yingtong Wu, Chao Zou, Ying Yu, Lin Gao, Huanan Zhang, Xinrui Gao, Qiang Li, Lu Wang, Jie Liu, Chaoqun Niu, Xueying Zhang, Sumei Hu, John R. Speakman
{"title":"Testing the carbohydrate-insulin model: Short-term metabolic responses to consumption of meals with varying glycemic index in healthy adults","authors":"Ying Liu, Huihui Mei, Li Xue, Chuanli Cheng, Yingtong Wu, Chao Zou, Ying Yu, Lin Gao, Huanan Zhang, Xinrui Gao, Qiang Li, Lu Wang, Jie Liu, Chaoqun Niu, Xueying Zhang, Sumei Hu, John R. Speakman","doi":"10.1016/j.cmet.2025.04.012","DOIUrl":"https://doi.org/10.1016/j.cmet.2025.04.012","url":null,"abstract":"(Cell Metabolism <em>37</em>, 606–615.e1–e3; March 4, 2025)","PeriodicalId":9840,"journal":{"name":"Cell metabolism","volume":"36 1","pages":""},"PeriodicalIF":29.0,"publicationDate":"2025-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143885420","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 : 2025-04-22DOI: 10.1016/j.cmet.2025.04.001
Yuki Tatekoshi, Amir Mahmoodzadeh, Jason S. Shapiro, Mingyang Liu, George M. Bianco, Ayumi Tatekoshi, Spencer Duncan Camp, Adam De Jesus, Navid Koleini, Santiago De La Torre, J. Andrew Wasserstrom, Wolfgang H. Dillmann, Benjamin R. Thomson, Kenneth C. Bedi, Kenneth B. Margulies, Samuel E. Weinberg, Hossein Ardehali
{"title":"Protein O-GlcNAcylation and hexokinase mitochondrial dissociation drive heart failure with preserved ejection fraction","authors":"Yuki Tatekoshi, Amir Mahmoodzadeh, Jason S. Shapiro, Mingyang Liu, George M. Bianco, Ayumi Tatekoshi, Spencer Duncan Camp, Adam De Jesus, Navid Koleini, Santiago De La Torre, J. Andrew Wasserstrom, Wolfgang H. Dillmann, Benjamin R. Thomson, Kenneth C. Bedi, Kenneth B. Margulies, Samuel E. Weinberg, Hossein Ardehali","doi":"10.1016/j.cmet.2025.04.001","DOIUrl":"https://doi.org/10.1016/j.cmet.2025.04.001","url":null,"abstract":"Heart failure with preserved ejection fraction (HFpEF) is a common cause of morbidity and mortality worldwide, but its pathophysiology remains unclear. Here, we report a mouse model of HFpEF and show that hexokinase (HK)-1 mitochondrial binding in endothelial cells (ECs) is critical for protein O-GlcNAcylation and the development of HFpEF. We demonstrate increased mitochondrial dislocation of HK1 within ECs in HFpEF mice. Mice with deletion of the mitochondrial-binding domain of HK1 spontaneously develop HFpEF and display impaired angiogenesis. Spatial proximity of dislocated HK1 and O-linked N-acetylglucosamine transferase (OGT) causes increased OGT activity, shifting the balance of the hexosamine biosynthetic pathway intermediates into the O-GlcNAcylation machinery. EC-specific overexpression of O-GlcNAcase and an OGT inhibitor reverse angiogenic defects and the HFpEF phenotype, highlighting the importance of protein O-GlcNAcylation in the development of HFpEF. Our study demonstrates a new mechanism for HFpEF through HK1 cellular localization and resultant protein O-GlcNAcylation, and provides a potential therapy for HFpEF.","PeriodicalId":9840,"journal":{"name":"Cell metabolism","volume":"62 1","pages":""},"PeriodicalIF":29.0,"publicationDate":"2025-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143857785","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 : 2025-04-22DOI: 10.1016/j.cmet.2025.03.017
Cuauhtemoc B. Ramirez, In Sook Ahn, Varvara I. Rubtsova, Ingrid Cely, Johnny Le, Joohwan Kim, Sunhee Jung, Miranda E. Kelly, Yeojin Kim, Hosung Bae, Won-Suk Song, Yasmine H. Alam, Guanglin Zhang, Graciel Diamante, Alina Chao, Lauren Hoffner, Alexis Anica, Izabelle Le, Miranda L. Lopez, Ian J. Tamburini, Cholsoon Jang
{"title":"Circulating glycerate predicts resilience to fructose-induced hepatic steatosis","authors":"Cuauhtemoc B. Ramirez, In Sook Ahn, Varvara I. Rubtsova, Ingrid Cely, Johnny Le, Joohwan Kim, Sunhee Jung, Miranda E. Kelly, Yeojin Kim, Hosung Bae, Won-Suk Song, Yasmine H. Alam, Guanglin Zhang, Graciel Diamante, Alina Chao, Lauren Hoffner, Alexis Anica, Izabelle Le, Miranda L. Lopez, Ian J. Tamburini, Cholsoon Jang","doi":"10.1016/j.cmet.2025.03.017","DOIUrl":"https://doi.org/10.1016/j.cmet.2025.03.017","url":null,"abstract":"Excessive intake of dietary fructose increases the risk of metabolic-dysfunction-associated steatotic liver disease (MASLD), cirrhosis, and cancers. However, what host factors determine disease vulnerability is incompletely understood. Here, we leverage genetically divergent mouse strains, mass spectrometry-based metabolomics, and <em>in vivo</em> isotope tracing, identifying circulating glycerate as a biomarker that predicts resilience to fructose-induced hepatic steatosis in both sexes. We found that the surge of circulating glycerate after an oral fructose provision reflects strong small-intestinal fructose catabolism. Such fructose clearance by the small intestine is linked to a weaker induction of hepatic <em>de novo</em> lipogenesis and steatosis upon chronic fructose exposure across strains. These data indicate the potential utility of an oral fructose tolerance test and circulating glycerate measurements to predict an individual's susceptibility to fructose-elicited steatotic liver and provide personalized dietary recommendations.","PeriodicalId":9840,"journal":{"name":"Cell metabolism","volume":"35 1","pages":""},"PeriodicalIF":29.0,"publicationDate":"2025-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143857781","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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