首页 > 最新文献

Cell metabolism最新文献

英文 中文
Missed signals: How PET imaging may fail to capture the addictive potential of ultra-processed foods 错过的信号:PET成像可能无法捕捉到超加工食品的潜在成瘾性
IF 29 1区 生物学 Q1 CELL BIOLOGY Pub Date : 2025-08-05 DOI: 10.1016/j.cmet.2025.06.007
Nicole M. Avena, Mark S. Gold, Ashley N. Gearhardt

Section snippets

Main text

This letter responds to the study by Darcey et al.1 The authors conclude that there was “no significant post-ingestive striatal dopamine response to an ultra-processed milkshake” and argue that this challenges the idea that ultra-processed foods (UPFs) drive overeating by triggering dopamine surges similar to those seen with drugs of abuse.1While we appreciate research aimed at understanding how UPFs affect the brain and their role in obesity and metabolic syndrome, we believe key

Declaration of interests

The authors declare no competing interests.
这封信是对Darcey等人的研究的回应。作者得出结论,“对超加工奶昔没有明显的摄入后纹状体多巴胺反应”,并认为这挑战了超加工食品(upf)通过引发多巴胺激增而导致暴饮暴食的观点,这与滥用药物相似。虽然我们赞赏旨在了解upf如何影响大脑及其在肥胖和代谢综合征中的作用的研究,但我们相信关键利益声明作者声明没有利益竞争。
{"title":"Missed signals: How PET imaging may fail to capture the addictive potential of ultra-processed foods","authors":"Nicole M. Avena, Mark S. Gold, Ashley N. Gearhardt","doi":"10.1016/j.cmet.2025.06.007","DOIUrl":"https://doi.org/10.1016/j.cmet.2025.06.007","url":null,"abstract":"<h2>Section snippets</h2><section><section><h2>Main text</h2>This letter responds to the study by Darcey et al.<sup>1</sup> The authors conclude that there was “no significant post-ingestive striatal dopamine response to an ultra-processed milkshake” and argue that this challenges the idea that ultra-processed foods (UPFs) drive overeating by triggering dopamine surges similar to those seen with drugs of abuse.<sup>1</sup>While we appreciate research aimed at understanding how UPFs affect the brain and their role in obesity and metabolic syndrome, we believe key</section></section><section><section><h2>Declaration of interests</h2>The authors declare no competing interests.</section></section>","PeriodicalId":9840,"journal":{"name":"Cell metabolism","volume":"1 1","pages":""},"PeriodicalIF":29.0,"publicationDate":"2025-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144778587","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
Glycogen shepherd guides the hidden trail of pentose phosphate pathway 糖原牧羊人引导戊糖磷酸途径的隐藏踪迹
IF 29 1区 生物学 Q1 CELL BIOLOGY Pub Date : 2025-08-05 DOI: 10.1016/j.cmet.2025.07.002
Lin Wang, Kaili Ma, Lianjun Zhang, Ping-Chih Ho
In a recent Molecular Cell study,1 Zhou et al. elucidated how glycogenolysis-derived glucose-1-phosphate mediates source-specific routing of glucose-6-phosphate into the pentose phosphate pathway through allosteric activation of glucose-6-phosphate dehydrogenase and liquid-liquid phase separation-mediated metabolic compartments. This compartmentalized distribution enables efficient reduced nicotinamide adenine dinucleotide phosphate (NADPH) generation from glycogenolytic flux, promoting Tm cell persistence by maintaining redox homeostasis.
在最近的一项Molecular Cell研究中,1 Zhou等人阐明了糖原分解衍生的葡萄糖-1-磷酸如何通过葡萄糖-6-磷酸脱氢酶的变乙酰激活和液-液相分离介导的代谢区室介导葡萄糖-6-磷酸进入戊糖磷酸途径的来源特异性途径。这种区室化的分布使糖原溶解通量产生的烟酰胺腺嘌呤二核苷酸磷酸(NADPH)有效减少,通过维持氧化还原稳态来促进Tm细胞的持久性。
{"title":"Glycogen shepherd guides the hidden trail of pentose phosphate pathway","authors":"Lin Wang, Kaili Ma, Lianjun Zhang, Ping-Chih Ho","doi":"10.1016/j.cmet.2025.07.002","DOIUrl":"https://doi.org/10.1016/j.cmet.2025.07.002","url":null,"abstract":"In a recent <em>Molecular Cell</em> study,<span><span><sup>1</sup></span></span> Zhou et al. elucidated how glycogenolysis-derived glucose-1-phosphate mediates source-specific routing of glucose-6-phosphate into the pentose phosphate pathway through allosteric activation of glucose-6-phosphate dehydrogenase and liquid-liquid phase separation-mediated metabolic compartments. This compartmentalized distribution enables efficient reduced nicotinamide adenine dinucleotide phosphate (NADPH) generation from glycogenolytic flux, promoting Tm cell persistence by maintaining redox homeostasis.","PeriodicalId":9840,"journal":{"name":"Cell metabolism","volume":"15 1","pages":""},"PeriodicalIF":29.0,"publicationDate":"2025-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144778433","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 peril of preconceived narratives 先入为主的叙述的危险
IF 29 1区 生物学 Q1 CELL BIOLOGY Pub Date : 2025-08-05 DOI: 10.1016/j.cmet.2025.06.006
Kevin D. Hall, Valerie L. Darcey

Section snippets

Main text

We had not anticipated that our recent paper in Cell Metabolism reporting surprisingly null results for one of its primary outcomes1 would cause so much consternation. Our empirical evidence ran against preconceived narratives (including our own) and caused a cascade of previously unimaginable events.Despite our paper emphasizing that our study’s “results do not imply that ultra-processed foods high in fat and sugar are not addictive,” it seems that several readers believe we suggested

Declaration of interests

The authors declare no competing interests.
我们没有预料到,我们最近在《细胞代谢》杂志上发表的一篇论文报告了一个令人惊讶的无效结果,这引起了如此大的恐慌。我们的经验证据与先入为主的叙述(包括我们自己的)相悖,并引发了一系列以前无法想象的事件。尽管我们的论文强调,我们的研究“结果并不意味着高脂肪和高糖的超加工食品不会上瘾”,但似乎有一些读者相信我们的建议。
{"title":"The peril of preconceived narratives","authors":"Kevin D. Hall, Valerie L. Darcey","doi":"10.1016/j.cmet.2025.06.006","DOIUrl":"https://doi.org/10.1016/j.cmet.2025.06.006","url":null,"abstract":"<h2>Section snippets</h2><section><section><h2>Main text</h2>We had not anticipated that our recent paper in <em>Cell Metabolism</em> reporting surprisingly null results for one of its primary outcomes<sup>1</sup> would cause so much consternation. Our empirical evidence ran against preconceived narratives (including our own) and caused a cascade of previously unimaginable events.Despite our paper emphasizing that our study’s “results do not imply that ultra-processed foods high in fat and sugar are not addictive,” it seems that several readers believe we suggested</section></section><section><section><h2>Declaration of interests</h2>The authors declare no competing interests.</section></section>","PeriodicalId":9840,"journal":{"name":"Cell metabolism","volume":"730 1","pages":""},"PeriodicalIF":29.0,"publicationDate":"2025-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144778586","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
Ultra-processed foods and dopamine: Parsing complexity beyond observed variability 超加工食品和多巴胺:分析观察到的变异性之外的复杂性
IF 29 1区 生物学 Q1 CELL BIOLOGY Pub Date : 2025-08-05 DOI: 10.1016/j.cmet.2025.06.008
Natasha Kim de Oliveira da Fonseca, Elisa Brietzke

Section snippets

Main text

The recent study by Darcey et al.1 offers a thought-provoking contribution to our understanding of how the human brain responds to ultra-processed foods, particularly in relation to striatal dopamine signaling and adiposity. Using a rigorous positron emission tomography (PET) imaging protocol, the authors report high interindividual variability and an absence of significant association between dopaminergic response and body fat. These findings challenge reductionist views of food addiction as a

Declaration of interests

The authors declare no competing interests.
Darcey等人最近的研究为我们理解人类大脑对超加工食品的反应,特别是纹状体多巴胺信号和肥胖之间的关系,提供了一个发人深省的贡献。使用严格的正电子发射断层扫描(PET)成像方案,作者报告了高度的个体差异和多巴胺能反应与体脂肪之间缺乏显着关联。这些发现挑战了将食物成瘾视为利益宣言的简化论者的观点。
{"title":"Ultra-processed foods and dopamine: Parsing complexity beyond observed variability","authors":"Natasha Kim de Oliveira da Fonseca, Elisa Brietzke","doi":"10.1016/j.cmet.2025.06.008","DOIUrl":"https://doi.org/10.1016/j.cmet.2025.06.008","url":null,"abstract":"<h2>Section snippets</h2><section><section><h2>Main text</h2>The recent study by Darcey et al.<sup>1</sup> offers a thought-provoking contribution to our understanding of how the human brain responds to ultra-processed foods, particularly in relation to striatal dopamine signaling and adiposity. Using a rigorous positron emission tomography (PET) imaging protocol, the authors report high interindividual variability and an absence of significant association between dopaminergic response and body fat. These findings challenge reductionist views of food addiction as a</section></section><section><section><h2>Declaration of interests</h2>The authors declare no competing interests.</section></section>","PeriodicalId":9840,"journal":{"name":"Cell metabolism","volume":"29 1","pages":""},"PeriodicalIF":29.0,"publicationDate":"2025-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144778583","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
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 Q1 CELL BIOLOGY 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

Section snippets

Main text

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

Acknowledgments

This work was supported by NIH 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 Japan Society for Promotion of Science (JSPS) Fellows 24KJ2039 to T.K.

Author contributions

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

Declaration of interests

The authors declare no competing interests.
胰高血糖素样肽-1受体(GLP-1R)激动剂,如semaglutide,代表了药物干预治疗肥胖的重大突破。与此同时,最近有人担心GLP-1R激动剂治疗会导致瘦质量的损失,潜在地损害身体功能和生活质量,特别是对那些易患肌肉减少症的人。在semaglutide的STEP-1试验中,瘦质量减少了6.92 kg,体重减轻了15.3 kg,表明这项工作得到了NIH拨款DK107397, DK127979, GM144613和AG074535给kf的支持;CA286584和AG065993交流电;和AG076075和AG086328资助M.J.D.和日本科学促进会(JSPS)研究员24KJ2039资助t.k.。, r.h.c., m.j.d., a.c.和K.F.构思了这个项目并设计了实验。t.k., r.h.c.和C.A.M.为这份手稿做了大部分实验。S.R.协助组织组织学分析。T.K.和K.F.写了手稿。这篇手稿经过了所有作者的审查、修改和批准,才得以出版。K.F.是这项工作的担保人,因此,他可以完全访问研究中的所有数据,并对研究的完整性和利益声明负责。作者声明没有竞争利益。
{"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 Q1 CELL BIOLOGY Pub Date : 2025-08-05 DOI: 10.1016/j.cmet.2025.07.005
Yan Yue, Shiping Li, Dezhi Mu
Atherosclerosis (AS) is an independent risk factor for vascular cognitive impairment (VCI). Zhang et al.1 revealed that foam cell-derived exosomes transmit redox imbalance and metabolic defects to microglia via the miR-101-3p-Nrf2-Slc2a1 axis, causing microglial dysfunction and exacerbating VCI, uncovering a peripheral-brain link and potential therapeutic targets for AS-induced VCI.
动脉粥样硬化(AS)是血管性认知障碍(VCI)的独立危险因素。Zhang等人1发现泡沫细胞衍生的外泌体通过mir -101- p3 - nrf2 - slc2a1轴将氧化还原失衡和代谢缺陷传递给小胶质细胞,导致小胶质细胞功能障碍并加剧VCI,揭示了as诱导的VCI的外周-脑联系和潜在的治疗靶点。
{"title":"Foam cell-derived exosomes: Messengers between atherosclerosis and microglia","authors":"Yan Yue, Shiping Li, Dezhi Mu","doi":"10.1016/j.cmet.2025.07.005","DOIUrl":"https://doi.org/10.1016/j.cmet.2025.07.005","url":null,"abstract":"Atherosclerosis (AS) is an independent risk factor for vascular cognitive impairment (VCI). Zhang et al.<span><span><sup>1</sup></span></span> revealed that foam cell-derived exosomes transmit redox imbalance and metabolic defects to microglia via the miR-101-3p-Nrf2-Slc2a1 axis, causing microglial dysfunction and exacerbating VCI, uncovering a peripheral-brain link and potential therapeutic targets for AS-induced VCI.","PeriodicalId":9840,"journal":{"name":"Cell metabolism","volume":"29 1","pages":""},"PeriodicalIF":29.0,"publicationDate":"2025-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144778610","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
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 Q1 CELL BIOLOGY 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
Glucose is essential for T cell proliferation and function, yet its specific metabolic roles in vivo remain poorly defined. Here, we identify glycosphingolipid (GSL) biosynthesis as a key pathway fueled by glucose that enables CD8+ T cell expansion and cytotoxic function in vivo. Using 13C-based stable isotope tracing, we demonstrate that CD8+ 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+ 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+ T cells display reduced granzyme expression, cytolytic activity, and tumor control in vivo. Together, our data establish GSL biosynthesis as a critical metabolic fate of glucose—beyond energy production—that is required for CD8+ T cell responses in vivo.
葡萄糖对T细胞的增殖和功能至关重要,但其在体内的具体代谢作用仍不清楚。在这里,我们确定鞘糖脂(GSL)的生物合成是葡萄糖促进CD8+ T细胞扩增和体内细胞毒性功能的关键途径。利用基于13c的稳定同位素示踪,我们证明CD8+效应T细胞利用葡萄糖合成尿苷二磷酸葡萄糖(UDP-Glc),这是糖原、聚糖和GSL生物合成的前体。通过靶向酶UDP-Glc焦磷酸化酶2 (UGP2), udp - gal -4- epimase (GALE)或UDP-Glc神经酰胺葡萄糖基转移酶(UGCG)抑制GSL的产生可损害CD8+ T细胞在病原体攻击下的扩增。在机制上,我们发现葡萄糖依赖的GSL生物合成是质膜脂筏完整性和最佳T细胞受体(TCR)信号传导所必需的。此外,ugcg缺陷的CD8+ T细胞在体内表现出颗粒酶表达、细胞溶解活性和肿瘤控制的降低。总之,我们的数据表明GSL生物合成是葡萄糖的关键代谢命运-超越能量生产-这是体内CD8+ T细胞反应所必需的。
{"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 Q1 CELL BIOLOGY 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
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.
l -乳酸参与代谢,包括Cori循环,但对d -乳酸知之甚少。我们发现,人类和肥胖小鼠的循环d -乳酸水平更高。d -乳酸比等摩尔l -乳酸更能提高小鼠肝糖原、甘油三酯和血糖。稳定同位素分析表明,d -乳酸在小鼠和肝细胞中代谢为丙酮酸、TCA中间体、脂质和葡萄糖。肠道菌群是血液d -乳酸的主要来源。用一种产生d -乳酸的菌株定植小鼠,使其血糖比产生l -乳酸的菌株更高。口服一种生物相容性聚合物,可以捕获肠道d -乳酸,迫使粪便排泄,以聚合物长度和剂量依赖的方式降低肥胖小鼠的血糖和胰岛素抵抗。这种d -乳酸陷阱降低了代谢功能障碍相关脂肪性肝病(MAFLD)/代谢功能障碍相关脂肪性肝炎(MASH)小鼠的肝脏炎症和纤维化。因此,微生物来源的d -乳酸有助于宿主葡萄糖和脂质代谢,可以被捕获以改善肥胖期间的代谢性疾病。
{"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 Q1 CELL BIOLOGY 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
Metabolic adaptations involved in tumor metastasis and immune evasion merit investigation. Here, using in vivo 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+ T cell cytotoxicity. Mechanistically, CD8+ 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+ T cell response by promoting Xu5P-responsive progenitor-like SLC35E2+ CD8+ exhausted T cells via tet methylcytosine dioxygenase 3 (TET3)-mediated DNA demethylation of the Tcf7 promoter. Clinically, elevated XYLB or blood Xu5P correlates with enhanced CD8+ 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.
参与肿瘤转移和免疫逃避的代谢适应值得研究。在这里,通过体内代谢CRISPR/Cas9基因敲除筛选,我们发现木糖激酶(XYLB)是一种肿瘤抑制因子,它通过产生木糖5-磷酸(Xu5P)来损害肺定植,从而促进CD8+ T细胞的细胞毒性。从机制上说,CD8+ T细胞表达相对较高水平的溶质载体家族35成员E2 (SLC35E2),这是植物Xu5P转运蛋白的同源物,促进Xu5P的摄取,随后加强五糖磷酸途径和糖酵解,以实现能量/氧化还原平衡。此外,我们发现Xu5P通过tet甲基胞嘧啶双加氧酶3 (TET3)介导的Tcf7启动子的DNA去甲基化,促进Xu5P应答的祖细胞样SLC35E2+ CD8+枯竭T细胞,从而增强CD8+ T细胞应答。在临床上,XYLB或血Xu5P升高与CD8+ T细胞疗效增强和转移减少相关。在小鼠模型中,补充或采用富含Xu5P的饮食可与抗pd -1治疗协同增强抗肿瘤免疫。这些发现为饮食干预转移性癌症的可能性提供了见解。
{"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 Q1 CELL BIOLOGY 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
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.
皮肤冷却导致热产生机制的激活,以抵消热量流失到环境中。在这里,我们的目的是了解冷刺激产热的变化在多大程度上可能是由寒战和非寒战产热(NST)的贡献差异以及与生物性别的相互作用驱动的。在健康男性和女性中使用一种新颖的平均皮肤温度夹紧技术,我们的数据显示,冷刺激的产热以皮肤温度依赖的方式随着颤抖和心肌氧化代谢的增加而增加。寒战和心肌产热也中度相关。相比之下,脂肪组织NST并没有随着皮肤温度的降低而线性增加。男性和女性表现出相似的体温调节反应,尽管女性表现出更明显的颤抖,因为下半身肌肉和运动单元的调动更多。因此,颤抖对冷诱导产热的贡献成比例,而脂肪组织产热则表现出全有或全无的反应。
{"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
期刊
Cell metabolism
全部 Acc. Chem. Res. ACS Applied Bio Materials ACS Appl. Electron. Mater. ACS Appl. Energy Mater. ACS Appl. Mater. Interfaces ACS Appl. Nano Mater. ACS Appl. Polym. Mater. ACS BIOMATER-SCI ENG ACS Catal. ACS Cent. Sci. ACS Chem. Biol. ACS Chemical Health & Safety ACS Chem. Neurosci. ACS Comb. Sci. ACS Earth Space Chem. ACS Energy Lett. ACS Infect. Dis. ACS Macro Lett. ACS Mater. Lett. ACS Med. Chem. Lett. ACS Nano ACS Omega ACS Photonics ACS Sens. ACS Sustainable Chem. Eng. ACS Synth. Biol. Anal. Chem. BIOCHEMISTRY-US Bioconjugate Chem. BIOMACROMOLECULES Chem. Res. Toxicol. Chem. Rev. Chem. Mater. CRYST GROWTH DES ENERG FUEL Environ. Sci. Technol. Environ. Sci. Technol. Lett. Eur. J. Inorg. Chem. IND ENG CHEM RES Inorg. Chem. J. Agric. Food. Chem. J. Chem. Eng. Data J. Chem. Educ. J. Chem. Inf. Model. J. Chem. Theory Comput. J. Med. Chem. J. Nat. Prod. J PROTEOME RES J. Am. Chem. Soc. LANGMUIR MACROMOLECULES Mol. Pharmaceutics Nano Lett. Org. Lett. ORG PROCESS RES DEV ORGANOMETALLICS J. Org. Chem. J. Phys. Chem. J. Phys. Chem. A J. Phys. Chem. B J. Phys. Chem. C J. Phys. Chem. Lett. Analyst Anal. Methods Biomater. Sci. Catal. Sci. Technol. Chem. Commun. Chem. Soc. Rev. CHEM EDUC RES PRACT CRYSTENGCOMM Dalton Trans. Energy Environ. Sci. ENVIRON SCI-NANO ENVIRON SCI-PROC IMP ENVIRON SCI-WAT RES Faraday Discuss. Food Funct. Green Chem. Inorg. Chem. Front. Integr. Biol. J. Anal. At. Spectrom. J. Mater. Chem. A J. Mater. Chem. B J. Mater. Chem. C Lab Chip Mater. Chem. Front. Mater. Horiz. MEDCHEMCOMM Metallomics Mol. Biosyst. Mol. Syst. Des. Eng. Nanoscale Nanoscale Horiz. Nat. Prod. Rep. New J. Chem. Org. Biomol. Chem. Org. Chem. Front. PHOTOCH PHOTOBIO SCI PCCP Polym. Chem.
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
0
微信
客服QQ
Book学术公众号 扫码关注我们
反馈
×
意见反馈
请填写您的意见或建议
请填写您的手机或邮箱
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
现在去查看 取消
×
提示
确定
Book学术官方微信
Book学术文献互助
Book学术文献互助群
群 号:604180095
Book学术
文献互助 智能选刊 最新文献 互助须知 联系我们:info@booksci.cn
Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。
Copyright © 2023 Book学术 All rights reserved.
ghs 京公网安备 11010802042870号 京ICP备2023020795号-1