Pub Date : 2025-08-27DOI: 10.1016/j.cmet.2025.08.001
Moubin Lin, Juan Wang, Yongshuai Chai, Xin Chen, Danyang Zhao, Zhangdan Xie, Jiebang Jiang, Hong Li, Li Huang, Siwei Xing, Dashi Qi, Xinyu Mei
Inflammation and its metabolic-network interactions generate novel regulatory molecules with translational implications. Here, we identify the immunometabolic crosstalk that generates homocysitaconate, a metabolite formed by homocysteine and itaconate adduction catalyzed by S-adenosyl-L-homocysteine hydrolase (AHCY). Homocysitaconate increases 152-fold during inflammation and exhibits anti-inflammatory effects. Mechanistically, homocysitaconate binds to the D312 residue of the pro-inflammatory protein methionyl-tRNA synthetase (MARS), inhibiting its function and reshaping methionine metabolism to feedback-brake the early activation of the N-homocysteinylation pathway. This metabolic switch facilitates NLR family pyrin domain-containing 3 (NLRP3) ubiquitination to control inflammation. Homocysitaconate demonstrates therapeutic effects in sepsis, high-fat-diet-induced inflammation, and colitis models. Boosting endogenous homocysitaconate synthesis through nicotinamide adenine dinucleotide (NAD+)-dependent AHCY activation (using nicotinamide riboside and pyruvate) also inhibits inflammation by targeting the MARS/NLRP3-N-homocysteinylation cascade. This study establishes homocysitaconate as an anti-inflammatory metabolite that serves as a homeostatic governor by reprogramming protein modification switches, introducing both metabolic timing regulation and clinical strategies to manage inflammatory complications.
炎症及其代谢网络相互作用产生具有翻译意义的新型调控分子。在这里，我们鉴定了产生同型半胱氨酸的免疫代谢串，同型半胱氨酸和s -腺苷- l-同型半胱氨酸水解酶（AHCY）催化的衣康酸内聚形成的代谢物。同半胱甘酸在炎症期间增加152倍，并表现出抗炎作用。机制上，同型半胱甘酸结合促炎蛋白蛋氨酸- trna合成酶（MARS）的D312残基，抑制其功能，重塑蛋氨酸代谢，反馈抑制n -同型半胱氨酸化途径的早期激活。这种代谢开关促进NLR家族含pyrin结构域3 （NLRP3）泛素化来控制炎症。高胱甘肽酸在脓毒症、高脂肪饮食引起的炎症和结肠炎模型中显示出治疗效果。通过烟酰胺腺嘌呤二核苷酸（NAD+）依赖的AHCY激活（使用烟酰胺核苷和丙酮酸）促进内源性高胱甘酸合成，也通过靶向MARS/ nlrp3 - n -同型半胱氨酸级联抑制炎症。本研究确立了同半胱甘肽酸作为一种抗炎代谢物，通过重编程蛋白质修饰开关作为一种体内平衡调节剂，引入代谢时间调节和临床策略来管理炎症并发症。
{"title":"Homocysitaconate controls inflammation through reshaping methionine metabolism and N-homocysteinylation","authors":"Moubin Lin, Juan Wang, Yongshuai Chai, Xin Chen, Danyang Zhao, Zhangdan Xie, Jiebang Jiang, Hong Li, Li Huang, Siwei Xing, Dashi Qi, Xinyu Mei","doi":"10.1016/j.cmet.2025.08.001","DOIUrl":"https://doi.org/10.1016/j.cmet.2025.08.001","url":null,"abstract":"Inflammation and its metabolic-network interactions generate novel regulatory molecules with translational implications. Here, we identify the immunometabolic crosstalk that generates homocysitaconate, a metabolite formed by homocysteine and itaconate adduction catalyzed by S-adenosyl-L-homocysteine hydrolase (AHCY). Homocysitaconate increases 152-fold during inflammation and exhibits anti-inflammatory effects. Mechanistically, homocysitaconate binds to the D312 residue of the pro-inflammatory protein methionyl-tRNA synthetase (MARS), inhibiting its function and reshaping methionine metabolism to feedback-brake the early activation of the N-homocysteinylation pathway. This metabolic switch facilitates NLR family pyrin domain-containing 3 (NLRP3) ubiquitination to control inflammation. Homocysitaconate demonstrates therapeutic effects in sepsis, high-fat-diet-induced inflammation, and colitis models. Boosting endogenous homocysitaconate synthesis through nicotinamide adenine dinucleotide (NAD<sup>+</sup>)-dependent AHCY activation (using nicotinamide riboside and pyruvate) also inhibits inflammation by targeting the MARS/NLRP3-N-homocysteinylation cascade. This study establishes homocysitaconate as an anti-inflammatory metabolite that serves as a homeostatic governor by reprogramming protein modification switches, introducing both metabolic timing regulation and clinical strategies to manage inflammatory complications.","PeriodicalId":9840,"journal":{"name":"Cell metabolism","volume":"24 1","pages":""},"PeriodicalIF":29.0,"publicationDate":"2025-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144906071","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-08-25DOI: 10.1016/j.cmet.2025.07.010
Dishu Zhou, Ying Chen, Panpan Liu, Kun Zhu, Juliet Holder-Haynes, S. Julie-Ann Lloyd, Cam Mong La, Inna I. Astapova, Seunghee Choa, Ying Xiong, Hosung Bae, Marlene Aguilar, Hongyuan Yang, Yu A. An, Zheng Sun, Mark A. Herman, Xia Gao, Liming Pei, Cholsoon Jang, Joshua D. Rabinowitz, Dongyin Guan
The circadian clock controls 24-h rhythmic processes. However, how genetic variations outside clock genes impact peripheral diurnal rhythms remains largely unknown. Here, we find that genetic variation contributes to different diurnal patterns of hepatic gene expression in both humans and mice. Nutritional challenges alter the rhythmicity of gene expression in mouse liver in a strain-specific manner. Remarkably, genetics and nutrition interdependently control more than 80% of rhythmic gene and enhancer-promoter interactions (E-PIs), with a noncanonical clock regulator, estrogen-related receptor gamma (ESRRγ), emerging as a top transcription factor during motif mining. Knockout of Esrrγ abolishes strain-specific metabolic processes in response to diet in mice, while single-nucleotide polymorphisms (SNPs) associated with rhythmic gene expression are enriched in E-PIs in steatotic human livers and correlate with lipid metabolism traits. These findings reveal a previously underappreciated temporal aspect of genetics-environment interaction in regulating lipid metabolic traits, with implications for individual variations in obesity-associated disease susceptibility and personalized chronotherapy.
{"title":"Genetics-nutrition interactions control diurnal enhancer-promoter dynamics and liver lipid metabolism","authors":"Dishu Zhou, Ying Chen, Panpan Liu, Kun Zhu, Juliet Holder-Haynes, S. Julie-Ann Lloyd, Cam Mong La, Inna I. Astapova, Seunghee Choa, Ying Xiong, Hosung Bae, Marlene Aguilar, Hongyuan Yang, Yu A. An, Zheng Sun, Mark A. Herman, Xia Gao, Liming Pei, Cholsoon Jang, Joshua D. Rabinowitz, Dongyin Guan","doi":"10.1016/j.cmet.2025.07.010","DOIUrl":"https://doi.org/10.1016/j.cmet.2025.07.010","url":null,"abstract":"The circadian clock controls 24-h rhythmic processes. However, how genetic variations outside clock genes impact peripheral diurnal rhythms remains largely unknown. Here, we find that genetic variation contributes to different diurnal patterns of hepatic gene expression in both humans and mice. Nutritional challenges alter the rhythmicity of gene expression in mouse liver in a strain-specific manner. Remarkably, genetics and nutrition interdependently control more than 80% of rhythmic gene and enhancer-promoter interactions (E-PIs), with a noncanonical clock regulator, estrogen-related receptor gamma (ESRRγ), emerging as a top transcription factor during motif mining. Knockout of <em>Esrrγ</em> abolishes strain-specific metabolic processes in response to diet in mice, while single-nucleotide polymorphisms (SNPs) associated with rhythmic gene expression are enriched in E-PIs in steatotic human livers and correlate with lipid metabolism traits. These findings reveal a previously underappreciated temporal aspect of genetics-environment interaction in regulating lipid metabolic traits, with implications for individual variations in obesity-associated disease susceptibility and personalized chronotherapy.","PeriodicalId":9840,"journal":{"name":"Cell metabolism","volume":"15 1","pages":""},"PeriodicalIF":29.0,"publicationDate":"2025-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144900555","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 : 2025-08-13DOI: 10.1016/j.cmet.2025.07.009
Robert Hansford, Sophie Buller, Anthony H. Tsang, Simon Benoit, Anna G. Roberts, Emmy Erskine, Thomas Brown, Valentina Pirro, Frank Reimann, Norio Harada, Nobuya Inagaki, Ricardo J. Samms, Johannes Broichhagen, David J. Hodson, Alice Adriaenssens, Soyoung Park, Clemence Blouet
The next generation of obesity medicines harness the activity of the glucose-dependent insulinotropic polypeptide and glucagon-like peptide 1 receptors (GIPR and GLP-1R), but their mechanism of action remains unclear. Here, we report that the GIPR is enriched in oligodendrocytes and GIPR signaling bidirectionally regulates oligodendrogenesis. In mice with adult-onset deletion of GIPR in oligodendrocytes, GIPR agonism fails to enhance the weight-loss effects of GLP-1R agonism. Mechanistically, GIPR agonism increases brain access of GLP-1R agonists, and GIPR signaling in oligodendrocytes is required for this effect. In addition, we show that vasopressin neurons of the paraventricular hypothalamus are necessary for the weight-loss response to GLP-1R activation, targeted by peripherally administered GLP-1R agonists via their axonal compartment, and this access is increased by activation of the GIPR in oligodendrocytes. Collectively, our findings identify a novel mechanism by which incretin therapies may function to promote synergistic weight loss in the management of excess adiposity.
{"title":"Glucose-dependent insulinotropic polypeptide receptor signaling in oligodendrocytes increases the weight-loss action of GLP-1R agonism","authors":"Robert Hansford, Sophie Buller, Anthony H. Tsang, Simon Benoit, Anna G. Roberts, Emmy Erskine, Thomas Brown, Valentina Pirro, Frank Reimann, Norio Harada, Nobuya Inagaki, Ricardo J. Samms, Johannes Broichhagen, David J. Hodson, Alice Adriaenssens, Soyoung Park, Clemence Blouet","doi":"10.1016/j.cmet.2025.07.009","DOIUrl":"https://doi.org/10.1016/j.cmet.2025.07.009","url":null,"abstract":"The next generation of obesity medicines harness the activity of the glucose-dependent insulinotropic polypeptide and glucagon-like peptide 1 receptors (GIPR and GLP-1R), but their mechanism of action remains unclear. Here, we report that the GIPR is enriched in oligodendrocytes and GIPR signaling bidirectionally regulates oligodendrogenesis. In mice with adult-onset deletion of GIPR in oligodendrocytes, GIPR agonism fails to enhance the weight-loss effects of GLP-1R agonism. Mechanistically, GIPR agonism increases brain access of GLP-1R agonists, and GIPR signaling in oligodendrocytes is required for this effect. In addition, we show that vasopressin neurons of the paraventricular hypothalamus are necessary for the weight-loss response to GLP-1R activation, targeted by peripherally administered GLP-1R agonists via their axonal compartment, and this access is increased by activation of the GIPR in oligodendrocytes. Collectively, our findings identify a novel mechanism by which incretin therapies may function to promote synergistic weight loss in the management of excess adiposity.","PeriodicalId":9840,"journal":{"name":"Cell metabolism","volume":"53 1","pages":""},"PeriodicalIF":29.0,"publicationDate":"2025-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144825263","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}
Diabetes mellitus (DM) is a known risk factor for pancreatic cancer, but the underlying mechanisms remain elusive. Here, we identify lactate-driven remodeling of tumor-associated Schwann cells (TASCs) as a key mediator of immunosuppression in diabetic pancreatic ductal adenocarcinoma (PDAC). Single-cell RNA sequencing revealed a c1-Mettl16+Cd276+Nectin2+ TASC subpopulation enriched in diabetic tumors that impairs CD8+ T cell function and promotes PD-1 resistance. Mechanistically, lactate enters TASCs via MCT1/MCT4, binds METTL16, and induces K269 lactylation, enhancing m6A-dependent CTCF stabilization and transcriptional activation of immunosuppressive ligands. Targeting METTL16 restores immune surveillance and sensitizes tumors to PD-1 blockade. Retrospective analyses confirmed therapeutic benefit in patients with diabetic PDAC receiving rosuvastatin. These findings uncover a lactate-METTL16-CTCF axis that links metabolic stress to epitranscriptomic reprogramming and immune evasion, offering a promising strategy to potentiate immunotherapy in metabolically dysregulated PDAC.
{"title":"Tumor-associated Schwann cell remodeling under metabolic stress via lactate sensing orchestrates pancreatic ductal adenocarcinoma development","authors":"Yihao Liu, Jiayu Lin, Zhengwei Yu, Xueying Li, Xueqi Lv, Pengyi Liu, Xiuqiao Sun, Zhen Zhang, Xia Gao, Keyan Sun, Dan Li, Jingfeng Li, Yang Liu, Yu Jiang, Siyi Zou, Jianping Lin, Baofa Sun, Da Fu, Baiyong Shen","doi":"10.1016/j.cmet.2025.07.008","DOIUrl":"https://doi.org/10.1016/j.cmet.2025.07.008","url":null,"abstract":"Diabetes mellitus (DM) is a known risk factor for pancreatic cancer, but the underlying mechanisms remain elusive. Here, we identify lactate-driven remodeling of tumor-associated Schwann cells (TASCs) as a key mediator of immunosuppression in diabetic pancreatic ductal adenocarcinoma (PDAC). Single-cell RNA sequencing revealed a c1-Mettl16+Cd276+Nectin2+ TASC subpopulation enriched in diabetic tumors that impairs CD8<sup>+</sup> T cell function and promotes PD-1 resistance. Mechanistically, lactate enters TASCs via MCT1/MCT4, binds METTL16, and induces K269 lactylation, enhancing m6A-dependent CTCF stabilization and transcriptional activation of immunosuppressive ligands. Targeting METTL16 restores immune surveillance and sensitizes tumors to PD-1 blockade. Retrospective analyses confirmed therapeutic benefit in patients with diabetic PDAC receiving rosuvastatin. These findings uncover a lactate-METTL16-CTCF axis that links metabolic stress to epitranscriptomic reprogramming and immune evasion, offering a promising strategy to potentiate immunotherapy in metabolically dysregulated PDAC.","PeriodicalId":9840,"journal":{"name":"Cell metabolism","volume":"143 1","pages":""},"PeriodicalIF":29.0,"publicationDate":"2025-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144819964","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 : 2025-08-06DOI: 10.1016/j.cmet.2025.07.007
Edgar Bernardo, Matías Gonzalo De Vas, Diego Balboa, Mirabai Cuenca-Ardura, Sílvia Bonàs-Guarch, Mercè Planas-Fèlix, Fanny Mollandin, Miquel Torrens-Dinarès, Miguel Angel Maestro, Javier García-Hurtado, Sonia Moratinos, Philippe Ravassard, Haiqiang Dou, Holger Heyn, Alexander van Oudenaarden, Nathalie Groen, Eelco de Koning, Christian Conrad, Roland Eils, Santiago Vernia, Jorge Ferrer
Type 2 diabetes (T2D) is a devastating chronic disease marked by pancreatic β cell dysfunction and insulin resistance, whose pathophysiology remains poorly understood. HNF1A, which encodes transcription factor hepatocyte nuclear factor-1 alpha, is the most commonly mutated gene in Mendelian diabetes. HNF1A also carries loss- or gain-of-function coding variants that respectively predispose to or protect against polygenic T2D. The mechanisms underlying HNF1A-deficient diabetes, however, are still unclear. We now demonstrate that diabetes arises from β cell-autonomous defects and identify direct β cell genomic targets of HNF1A. This uncovered a regulatory axis where HNF1A controls transcription of A1CF, which orchestrates an RNA splicing program encompassing genes that regulate β cell function. This HNF1A-A1CF transcription-splicing axis is suppressed in β cells from T2D individuals, while genetic variants reducing pancreatic islet A1CF are associated with increased glycemia and T2D susceptibility. Our findings, therefore, identify a linear hierarchy that coordinates β cell-specific transcription and splicing programs and link this pathway to T2D pathogenesis.
{"title":"HNF1A and A1CF coordinate a beta cell transcription-splicing axis that is disrupted in type 2 diabetes","authors":"Edgar Bernardo, Matías Gonzalo De Vas, Diego Balboa, Mirabai Cuenca-Ardura, Sílvia Bonàs-Guarch, Mercè Planas-Fèlix, Fanny Mollandin, Miquel Torrens-Dinarès, Miguel Angel Maestro, Javier García-Hurtado, Sonia Moratinos, Philippe Ravassard, Haiqiang Dou, Holger Heyn, Alexander van Oudenaarden, Nathalie Groen, Eelco de Koning, Christian Conrad, Roland Eils, Santiago Vernia, Jorge Ferrer","doi":"10.1016/j.cmet.2025.07.007","DOIUrl":"https://doi.org/10.1016/j.cmet.2025.07.007","url":null,"abstract":"Type 2 diabetes (T2D) is a devastating chronic disease marked by pancreatic β cell dysfunction and insulin resistance, whose pathophysiology remains poorly understood. <em>HNF1A</em>, which encodes transcription factor hepatocyte nuclear factor-1 alpha, is the most commonly mutated gene in Mendelian diabetes. <em>HNF1A</em> also carries loss- or gain-of-function coding variants that respectively predispose to or protect against polygenic T2D. The mechanisms underlying HNF1A-deficient diabetes, however, are still unclear. We now demonstrate that diabetes arises from β cell-autonomous defects and identify direct β cell genomic targets of HNF1A. This uncovered a regulatory axis where HNF1A controls transcription of <em>A1CF</em>, which orchestrates an RNA splicing program encompassing genes that regulate β cell function. This <em>HNF1A</em>-<em>A1CF</em> transcription-splicing axis is suppressed in β cells from T2D individuals, while genetic variants reducing pancreatic islet <em>A1CF</em> are associated with increased glycemia and T2D susceptibility. Our findings, therefore, identify a linear hierarchy that coordinates β cell-specific transcription and splicing programs and link this pathway to T2D pathogenesis.","PeriodicalId":9840,"journal":{"name":"Cell metabolism","volume":"1 1","pages":""},"PeriodicalIF":29.0,"publicationDate":"2025-08-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144792323","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.2025.06.005
Eugenio Barone, D. Allan Butterfield
Insulin resistance is a risk factor for Alzheimer’s disease (AD). Chen et al.1 show that microglial insulin signaling is essential for metabolic homeostasis and immune regulation, while insulin resistance impairs Aβ clearance and promotes neuroinflammation in AD. Their findings reframe AD pathogenesis through a cell-type-specific lens.
{"title":"Insulin signaling in microglia: A metabolic switch controlling neuroinflammation and amyloid pathology in Alzheimer’s disease","authors":"Eugenio Barone, D. Allan Butterfield","doi":"10.1016/j.cmet.2025.06.005","DOIUrl":"https://doi.org/10.1016/j.cmet.2025.06.005","url":null,"abstract":"Insulin resistance is a risk factor for Alzheimer’s disease (AD). Chen et al.<span><span><sup>1</sup></span></span> show that microglial insulin signaling is essential for metabolic homeostasis and immune regulation, while insulin resistance impairs Aβ clearance and promotes neuroinflammation in AD. Their findings reframe AD pathogenesis through a cell-type-specific lens.","PeriodicalId":9840,"journal":{"name":"Cell metabolism","volume":"27 1","pages":""},"PeriodicalIF":29.0,"publicationDate":"2025-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144778459","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.2025.07.003
Sharmili Edwin Thanarajah, Sita Arjune, Ruth Hanssen
Despite advances in elucidating obesity pathophysiology, predicting individual responses to weight loss interventions remains challenging. Cifuentes et al.1 developed a predictive model integrating genetic risk scores and anthropometric parameters to estimate caloric intake to satiation, demonstrating potential in forecasting weight loss trajectories with phentermine-topiramate and liraglutide therapies.
{"title":"Calories to satiation—A new predictor of anti-obesity therapy outcome?","authors":"Sharmili Edwin Thanarajah, Sita Arjune, Ruth Hanssen","doi":"10.1016/j.cmet.2025.07.003","DOIUrl":"https://doi.org/10.1016/j.cmet.2025.07.003","url":null,"abstract":"Despite advances in elucidating obesity pathophysiology, predicting individual responses to weight loss interventions remains challenging. Cifuentes et al.<span><span><sup>1</sup></span></span> developed a predictive model integrating genetic risk scores and anthropometric parameters to estimate caloric intake to satiation, demonstrating potential in forecasting weight loss trajectories with phentermine-topiramate and liraglutide therapies.","PeriodicalId":9840,"journal":{"name":"Cell metabolism","volume":"20 1","pages":""},"PeriodicalIF":29.0,"publicationDate":"2025-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144778588","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.2025.06.007
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}
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