Pub Date : 2025-08-05DOI: 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
{"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}
Pub Date : 2025-08-05DOI: 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.
Pub Date : 2025-08-05DOI: 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
{"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}
Pub Date : 2025-08-05DOI: 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
{"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}
Pub Date : 2025-08-05DOI: 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
{"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}
Pub Date : 2025-08-05DOI: 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.
{"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}
Pub Date : 2025-08-05DOI: 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.
{"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}
Pub Date : 2025-07-29DOI: 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.
{"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}
Pub Date : 2025-07-17DOI: 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.
{"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}
Pub Date : 2025-07-16DOI: 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.
{"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}
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