Cell metabolism最新文献_第4页

Unexpected effects of semaglutide on skeletal muscle mass and force-generating capacity in mice 西马鲁肽对小鼠骨骼肌质量和发力能力的意外影响

IF 29 1区生物学

Cell metabolism Pub Date : 2025-08-05 DOI: 10.1016/j.cmet.2025.07.004

Takuya Karasawa, Ran Hee Choi, Cesar A. Meza, Subhasmita Rout, Micah J. Drummond, Amandine Chaix, Katsuhiko Funai

{"title":"Unexpected effects of semaglutide on skeletal muscle mass and force-generating capacity in mice","authors":"Takuya Karasawa, Ran Hee Choi, Cesar A. Meza, Subhasmita Rout, Micah J. Drummond, Amandine Chaix, Katsuhiko Funai","doi":"10.1016/j.cmet.2025.07.004","DOIUrl":"https://doi.org/10.1016/j.cmet.2025.07.004","url":null,"abstract":"<h2>Section snippets</h2><section><section><h2>Main text</h2>Glucagon-like peptide-1 receptor (GLP-1R) agonists, such as semaglutide, represent a significant breakthrough in pharmacological interventions to treat obesity. Meanwhile, there have been recent concerns that GLP-1R agonist treatment leads to a loss of lean mass, potentially compromising physical functions and quality of life, particularly in those susceptible to sarcopenia. In the STEP-1 trial of semaglutide, lean mass was reduced by 6.92 kg with a weight reduction of 15.3 kg, indicating that</section></section><section><section><h2>Acknowledgments</h2>This work was supported by <span>NIH</span> grants DK107397, DK127979, GM144613, and AG074535 to K.F.; CA286584 and AG065993 to A.C.; and AG076075 and AG086328 to M.J.D. and the grant-in-aid for <span>Japan Society for Promotion of Science</span> (<span>JSPS</span>) Fellows 24KJ2039 to T.K.</section></section><section><section><h2>Author contributions</h2>T.K., R.H.C., M.J.D., A.C., and K.F. conceived the project and designed the experiments. T.K., R.H.C., and C.A.M. conducted the majority of experiments for this manuscript. S.R. assisted with tissue histological analyses. T.K. and K.F. wrote the manuscript. This manuscript was reviewed, revised, and given approval by all authors for publication. K.F. is the guarantor of this work and, as such, has full access to all the data in the study and takes responsibility for the integrity and the</section></section><section><section><h2>Declaration of interests</h2>The authors declare no competing interests.</section></section>","PeriodicalId":9840,"journal":{"name":"Cell metabolism","volume":"46 1","pages":""},"PeriodicalIF":29.0,"publicationDate":"2025-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144778581","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

Foam cell-derived exosomes: Messengers between atherosclerosis and microglia 泡沫细胞衍生外泌体：动脉粥样硬化和小胶质细胞之间的信使

IF 29 1区生物学

Cell metabolism Pub Date : 2025-08-05 DOI: 10.1016/j.cmet.2025.07.005

Yan Yue, Shiping Li, Dezhi Mu

引用次数: 0

Glucose-dependent glycosphingolipid biosynthesis fuels CD8+ T cell function and tumor control 葡萄糖依赖性鞘糖脂生物合成促进CD8+ T细胞功能和肿瘤控制

IF 29 1区生物学

Cell metabolism Pub Date : 2025-08-05 DOI: 10.1016/j.cmet.2025.07.006

Joseph Longo, Lisa M. DeCamp, Brandon M. Oswald, Robert Teis, Alfredo Reyes-Oliveras, Michael S. Dahabieh, Abigail E. Ellis, Michael P. Vincent, Hannah Damico, Kristin L. Gallik, Nicole M. Foy, Shelby E. Compton, Colt D. Capan, Kelsey S. Williams, Corinne R. Esquibel, Zachary B. Madaj, Hyoungjoo Lee, Dominic G. Roy, Connie M. Krawczyk, Brian B. Haab, Russell G. Jones

{"title":"Glucose-dependent glycosphingolipid biosynthesis fuels CD8+ T cell function and tumor control","authors":"Joseph Longo, Lisa M. DeCamp, Brandon M. Oswald, Robert Teis, Alfredo Reyes-Oliveras, Michael S. Dahabieh, Abigail E. Ellis, Michael P. Vincent, Hannah Damico, Kristin L. Gallik, Nicole M. Foy, Shelby E. Compton, Colt D. Capan, Kelsey S. Williams, Corinne R. Esquibel, Zachary B. Madaj, Hyoungjoo Lee, Dominic G. Roy, Connie M. Krawczyk, Brian B. Haab, Russell G. Jones","doi":"10.1016/j.cmet.2025.07.006","DOIUrl":"https://doi.org/10.1016/j.cmet.2025.07.006","url":null,"abstract":"Glucose is essential for T cell proliferation and function, yet its specific metabolic roles <em>in vivo</em> remain poorly defined. Here, we identify glycosphingolipid (GSL) biosynthesis as a key pathway fueled by glucose that enables CD8<sup>+</sup> T cell expansion and cytotoxic function <em>in vivo</em>. Using <sup>13</sup>C-based stable isotope tracing, we demonstrate that CD8<sup>+</sup> effector T cells use glucose to synthesize uridine diphosphate-glucose (UDP-Glc), a precursor for glycogen, glycan, and GSL biosynthesis. Inhibiting GSL production by targeting the enzymes UDP-Glc pyrophosphorylase 2 (UGP2), UDP-Gal-4-epimerase (GALE), or UDP-Glc ceramide glucosyltransferase (UGCG) impairs CD8<sup>+</sup> T cell expansion upon pathogen challenge. Mechanistically, we show that glucose-dependent GSL biosynthesis is required for plasma membrane lipid raft integrity and optimal T cell receptor (TCR) signaling. Moreover, UGCG-deficient CD8<sup>+</sup> T cells display reduced granzyme expression, cytolytic activity, and tumor control <em>in vivo</em>. Together, our data establish GSL biosynthesis as a critical metabolic fate of glucose—beyond energy production—that is required for CD8<sup>+</sup> T cell responses <em>in vivo</em>.","PeriodicalId":9840,"journal":{"name":"Cell metabolism","volume":"95 1","pages":""},"PeriodicalIF":29.0,"publicationDate":"2025-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144778591","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

Gut substrate trap of D-lactate from microbiota improves blood glucose and fatty liver disease in obese mice 肠道底物捕获来自微生物群的d -乳酸改善肥胖小鼠的血糖和脂肪肝疾病

IF 29 1区生物学

Cell metabolism Pub Date : 2025-07-29 DOI: 10.1016/j.cmet.2025.07.001

Han Fang, Fernando F. Anhê, Dana Kukje Zada, Nicole G. Barra, Rodrigo Rodrigues e-Lacerda, Breanne T. McAlpin, Ryan Wylie, Line Berthiaume, Étienne Audet-Walsh, Conor O’Dwyer, Peyman Ghorbani, Morgan D. Fullerton, Claudia Gagnon, André Tchernof, André Marette, Jonathan D. Schertzer

{"title":"Gut substrate trap of D-lactate from microbiota improves blood glucose and fatty liver disease in obese mice","authors":"Han Fang, Fernando F. Anhê, Dana Kukje Zada, Nicole G. Barra, Rodrigo Rodrigues e-Lacerda, Breanne T. McAlpin, Ryan Wylie, Line Berthiaume, Étienne Audet-Walsh, Conor O’Dwyer, Peyman Ghorbani, Morgan D. Fullerton, Claudia Gagnon, André Tchernof, André Marette, Jonathan D. Schertzer","doi":"10.1016/j.cmet.2025.07.001","DOIUrl":"https://doi.org/10.1016/j.cmet.2025.07.001","url":null,"abstract":"L-lactate participates in metabolism, including the Cori cycle, but less is known about D-lactate. We found that circulating D-lactate was higher in humans and mice with obesity. D-lactate increased hepatic glycogen, triglycerides, and blood glucose more than equimolar L-lactate in mice. Stable isotope analyses showed that D-lactate is metabolized in mice and in hepatocytes to pyruvate, TCA intermediates, lipids, and glucose. The gut microbiota is the main source of blood D-lactate. Colonization of mice with a bacterial strain that produced D-lactate elevated blood glucose more than an L-lactate producer. Oral delivery of a biocompatible polymer that traps gut D-lactate, forcing fecal excretion, lowered blood glucose and insulin resistance in obese mice in a polymer length- and dose-dependent manner. This D-lactate trap lowered hepatic inflammation and fibrosis in mice with metabolic dysfunction-associated fatty liver disease (MAFLD)/metabolic dysfunction-associated steatohepatitis (MASH). Therefore, microbial-derived D-lactate contributes to host glucose and lipid metabolism and can be trapped to improve metabolic disease during obesity.","PeriodicalId":9840,"journal":{"name":"Cell metabolism","volume":"72 1","pages":""},"PeriodicalIF":29.0,"publicationDate":"2025-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144720254","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

Xylulose 5-phosphate fosters sustained antitumor activity of progenitor-like exhausted SLC35E2+ CD8+ T effector cells 5-磷酸木糖糖促进祖细胞样衰竭SLC35E2+ CD8+ T效应细胞的持续抗肿瘤活性

IF 29 1区生物学

Cell metabolism Pub Date : 2025-07-17 DOI: 10.1016/j.cmet.2025.06.011

Tiezhu Shi, Jialiang Shao, Yufeng Ding, Hong Tang, Xiangyin Tan, Sisi Zhou, Shaoqing Yu, Xiang Wang, Guanzhen Yu, Ninghan Feng, Xiongjun Wang

{"title":"Xylulose 5-phosphate fosters sustained antitumor activity of progenitor-like exhausted SLC35E2+ CD8+ T effector cells","authors":"Tiezhu Shi, Jialiang Shao, Yufeng Ding, Hong Tang, Xiangyin Tan, Sisi Zhou, Shaoqing Yu, Xiang Wang, Guanzhen Yu, Ninghan Feng, Xiongjun Wang","doi":"10.1016/j.cmet.2025.06.011","DOIUrl":"https://doi.org/10.1016/j.cmet.2025.06.011","url":null,"abstract":"Metabolic adaptations involved in tumor metastasis and immune evasion merit investigation. Here, using <em>in vivo</em> metabolic CRISPR/Cas9 knockout screening, we identified xylulokinase (XYLB) as a tumor suppressor that impairs lung colonialization by producing xylulose 5-phosphate (Xu5P), which promotes CD8<sup>+</sup> T cell cytotoxicity. Mechanistically, CD8<sup>+</sup> T cells express relatively high levels of solute carrier family 35 member E2 (SLC35E2), a homolog of the plant Xu5P transporter, to facilitate Xu5P uptake and subsequently intensify the pentose phosphate pathway and glycolysis for energy/redox balance. Furthermore, we revealed that Xu5P potentiates CD8<sup>+</sup> T cell response by promoting Xu5P-responsive progenitor-like SLC35E2<sup>+</sup> CD8<sup>+</sup> exhausted T cells via tet methylcytosine dioxygenase 3 (TET3)-mediated DNA demethylation of the <em>Tcf7</em> promoter. Clinically, elevated XYLB or blood Xu5P correlates with enhanced CD8<sup>+</sup> T cell efficacy and reduced metastasis. In murine models, Xu5P supplementation or adopting Xu5P-rich diets synergizes with anti-PD-1 therapy to enhance antitumor immunity. These findings offer insights into the potentiality of dietary interventions for metastatic cancer.","PeriodicalId":9840,"journal":{"name":"Cell metabolism","volume":"14 1","pages":""},"PeriodicalIF":29.0,"publicationDate":"2025-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144645740","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

Shivering, but not adipose tissue thermogenesis, increases as a function of mean skin temperature in cold-exposed men and women 暴露在寒冷环境中的男性和女性，随着平均皮肤温度的增加，寒战（而非脂肪组织产热）会增加

IF 29 1区生物学

Cell metabolism Pub Date : 2025-07-16 DOI: 10.1016/j.cmet.2025.06.010

Lauralyne Dumont, Gabriel Richard, Romain Espagnet, Frédérique Frisch, Mélanie Fortin, Arnaud Samson, Jonathan Bouchard, Réjean Fontaine, Etienne Croteau, Serge Phoenix, Stéphanie Dubreuil, Brigitte Guérin, Éric E. Turcotte, André C. Carpentier, Denis P. Blondin

{"title":"Shivering, but not adipose tissue thermogenesis, increases as a function of mean skin temperature in cold-exposed men and women","authors":"Lauralyne Dumont, Gabriel Richard, Romain Espagnet, Frédérique Frisch, Mélanie Fortin, Arnaud Samson, Jonathan Bouchard, Réjean Fontaine, Etienne Croteau, Serge Phoenix, Stéphanie Dubreuil, Brigitte Guérin, Éric E. Turcotte, André C. Carpentier, Denis P. Blondin","doi":"10.1016/j.cmet.2025.06.010","DOIUrl":"https://doi.org/10.1016/j.cmet.2025.06.010","url":null,"abstract":"Skin cooling results in the activation of heat-generating mechanisms to counteract heat lost to the environment. Here, we aim to understand the extent to which variations in cold-stimulated heat production may be driven by differences in the contribution of shivering and non-shivering thermogenesis (NST) and the interaction with biological sex. Using a novel mean skin temperature clamping technique in healthy men and women, our data show that cold-stimulated heat production rises with increasing shivering and myocardial oxidative metabolism in a skin temperature-dependent fashion. Shivering and myocardial thermogenesis were also moderately associated. By contrast, adipose tissue NST did not increase in a linear manner to reductions in skin temperature. Men and women displayed similar thermoregulatory responses, although women presented more pronounced shivering through a greater recruitment of lower-body muscles and a greater number of motor units recruited. Thus, shivering contributes proportionally to cold-induced thermogenesis, whereas adipose tissue thermogenesis displays an all-or-none response.","PeriodicalId":9840,"journal":{"name":"Cell metabolism","volume":"16 1","pages":""},"PeriodicalIF":29.0,"publicationDate":"2025-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144640632","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

Localized GLP1 receptor pre-internalization directs pancreatic alpha cell to beta cell communication 局部GLP1受体预内化指导胰腺α细胞与β细胞之间的通讯

IF 29 1区生物学

Cell metabolism Pub Date : 2025-07-14 DOI: 10.1016/j.cmet.2025.06.009

Jason C.L. Tong, Charlotte Frazer-Morris, Ali H. Shilleh, Katrina Viloria, Anne de Bray, Adithya Muraleedaran Nair, Paul R.V. Johnson, Rebecca Spiers, Ahmad Kobiita, Oladapo E. Olaniru, Shanta J. Persaud, Robert Hauffe, André Kleinridders, Carsten Schultz, C. Bruce Verchere, Canqi Cui, Jonathan E. Campbell, Malgorzata Cyranka, Alexey Epanchintsev, Carina Ämmälä, David J. Hodson

{"title":"Localized GLP1 receptor pre-internalization directs pancreatic alpha cell to beta cell communication","authors":"Jason C.L. Tong, Charlotte Frazer-Morris, Ali H. Shilleh, Katrina Viloria, Anne de Bray, Adithya Muraleedaran Nair, Paul R.V. Johnson, Rebecca Spiers, Ahmad Kobiita, Oladapo E. Olaniru, Shanta J. Persaud, Robert Hauffe, André Kleinridders, Carsten Schultz, C. Bruce Verchere, Canqi Cui, Jonathan E. Campbell, Malgorzata Cyranka, Alexey Epanchintsev, Carina Ämmälä, David J. Hodson","doi":"10.1016/j.cmet.2025.06.009","DOIUrl":"https://doi.org/10.1016/j.cmet.2025.06.009","url":null,"abstract":"Pancreatic alpha cells modulate beta cell function in a paracrine manner through the release of glucagon. However, the detailed molecular architecture underlying alpha-to-beta cell regulation remains poorly characterized. Here, we show that the glucagon-like peptide-1 receptor (GLP1R) is enriched as nanodomains on beta cell membranes that contact alpha cells, in keeping with increased single-molecule transcript expression. At low glucose, beta cells next to alpha cells directly sense micromolar glucagon release by pre-internalizing GLP1R. Pre-internalized GLP1R is associated with earlier beta cell Ca<sup>2+</sup> responses to high glucose, which are then propagated across the islet. Beta cells adjacent to alpha cells are more secretory than beta cells next to other beta cells. Localized GLP1R signaling occurs <em>in vitro</em> and <em>in vivo</em>, is operative in the post-prandial state, and GLP1R contacts decrease between beta cells and alpha cells during metabolic stress. Thus, we detail a regulated pathway through which glucagon modulates insulin release.","PeriodicalId":9840,"journal":{"name":"Cell metabolism","volume":"29 1","pages":""},"PeriodicalIF":29.0,"publicationDate":"2025-07-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144622478","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

Microbial riboflavin inhibits ceramide synthase 3 to lower ceramide (d18:1/26:0) and delay colorectal cancer progression 微生物核黄素抑制神经酰胺合成酶3降低神经酰胺（d18:1/26:0），延缓结直肠癌进展

IF 29 1区生物学

Cell metabolism Pub Date : 2025-07-02 DOI: 10.1016/j.cmet.2025.06.002

Ruize Qu, Yi Zhang, Bora Kim, Guangyi Zeng, Pengcheng Wang, Weike Shaoyong, Ying Huang, Wanwan Guo, Yang Chen, Ping Wang, Qing Yang, Siyi Lu, Xin Zhou, Jing Weng, Jinkun Xu, Jun Lin, Kai Wang, Yanpeng Ma, Shogo Takahashi, Yuhong Luo, Lulu Sun

{"title":"Microbial riboflavin inhibits ceramide synthase 3 to lower ceramide (d18:1/26:0) and delay colorectal cancer progression","authors":"Ruize Qu, Yi Zhang, Bora Kim, Guangyi Zeng, Pengcheng Wang, Weike Shaoyong, Ying Huang, Wanwan Guo, Yang Chen, Ping Wang, Qing Yang, Siyi Lu, Xin Zhou, Jing Weng, Jinkun Xu, Jun Lin, Kai Wang, Yanpeng Ma, Shogo Takahashi, Yuhong Luo, Lulu Sun","doi":"10.1016/j.cmet.2025.06.002","DOIUrl":"https://doi.org/10.1016/j.cmet.2025.06.002","url":null,"abstract":"Ceramide metabolism dysregulation links to colorectal cancer (CRC) progression, yet the mechanism remains unknown. d18:1/26:0 ceramide (C26) levels were elevated in patients with CRC and mouse models, which activated epidermal growth factor receptor (EGFR) by binding its extracellular region to promote cancer cell proliferation. The rise of C26 levels was mainly driven by heightened ceramide synthase 3 (CERS3) activity. High CERS3 expression generally accelerated tumor progression, yet some patients exhibited significant heterogeneity, suggesting endogenous metabolites available to affect CERS3 activity. We found that the abundance of <em>Bacteroides cellulosilyticus</em> affects tumor heterogeneity by producing riboflavin that inhibits CERS3 activity, thus delaying CRC progression. Moreover, aclidinium bromide, an FDA-approved drug, exhibited significant inhibitory effects on CERS3 activity, suggesting its potential application in CRC treatment. These findings elucidate the metabolic pathways and mechanisms underlying ceramide’s impact on CRC, highlighting that targeting CERS3 inhibition represents a promising therapeutic strategy for CRC.","PeriodicalId":9840,"journal":{"name":"Cell metabolism","volume":"50 1","pages":""},"PeriodicalIF":29.0,"publicationDate":"2025-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144533897","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

Muscle needs NAD, but how much? 肌肉需要NAD，但需要多少呢？

IF 29 1区生物学

Cell metabolism Pub Date : 2025-07-01 DOI: 10.1016/j.cmet.2025.06.001

David W. Frederick, Joseph P. McGaunn, Joseph A. Baur

引用次数: 0

The NARly side of whole-body NAD homeostasis 全身NAD内稳态的早期方面

IF 29 1区生物学

Cell metabolism Pub Date : 2025-07-01 DOI: 10.1016/j.cmet.2025.06.003

Charles Brenner

引用次数: 0