Cell metabolismPub Date : 2026-04-01DOI: 10.1016/j.cmet.2026.03.018
Thomas Marjot, Kieran Smith, Felix Westcott, Sarah White, Elspeth Johnson, Nikola Srnic, Amy Barrett, Ellis Hall, Kate Gralton, Kaitlyn Dennis, Hamish Miller, Riccardo Pofi, Jeremy F.L. Cobbold, Rebecca Richmond, Fredrik Karpe, Ronnie Blazev, Matthew J. Watt, Benjamin L. Parker, Leanne Hodson, David W. Ray, Jeremy W. Tomlinson
{"title":"Human MASLD is a diurnal disease driven by multisystem insulin resistance and reduced insulin availability at night","authors":"Thomas Marjot, Kieran Smith, Felix Westcott, Sarah White, Elspeth Johnson, Nikola Srnic, Amy Barrett, Ellis Hall, Kate Gralton, Kaitlyn Dennis, Hamish Miller, Riccardo Pofi, Jeremy F.L. Cobbold, Rebecca Richmond, Fredrik Karpe, Ronnie Blazev, Matthew J. Watt, Benjamin L. Parker, Leanne Hodson, David W. Ray, Jeremy W. Tomlinson","doi":"10.1016/j.cmet.2026.03.018","DOIUrl":"https://doi.org/10.1016/j.cmet.2026.03.018","url":null,"abstract":"(Cell Metabolism <em>38</em>, 474–492.e1–e6; March 3, 2026)","PeriodicalId":9840,"journal":{"name":"Cell metabolism","volume":"61 1","pages":""},"PeriodicalIF":29.0,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147586416","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Cell metabolismPub Date : 2026-04-01DOI: 10.1016/j.cmet.2026.03.003
Ting-Ting Wang, Yan-Jia Luo, Wen Feng, Lian-Xiang Jiang, Qing-Song Yu, Yu-Ting He, Lizhi Guan, Bing-Qian Zhu, Hong Jiang, Min Li, Ruixin Liu, Jing Wang, Ya-Dong Li
{"title":"Gut microbial metabolism via hippocampal indole-AhR signaling regulates emotional symptoms","authors":"Ting-Ting Wang, Yan-Jia Luo, Wen Feng, Lian-Xiang Jiang, Qing-Song Yu, Yu-Ting He, Lizhi Guan, Bing-Qian Zhu, Hong Jiang, Min Li, Ruixin Liu, Jing Wang, Ya-Dong Li","doi":"10.1016/j.cmet.2026.03.003","DOIUrl":"https://doi.org/10.1016/j.cmet.2026.03.003","url":null,"abstract":"Gut microbiota modulate emotion, yet mechanistic insight and therapeutic targets remain limited. Here, we identify reduced gut microbiota-derived indole causally modulating emotion through hippocampal aryl hydrocarbon receptor (AhR). We found that decreased abundance of <em>Alistipes shahii</em> reduced intestinal indole levels via loss of tryptophanase, the rate-limiting step for indole production in microbial tryptophan metabolism, in irritable bowel syndrome (IBS) patients and model mice. In the brain, indole acts via AhR, which is enriched in the ventral dentate gyrus (vDG), a hub in regulating emotion. Reduced indole diminished nuclear AhR expression and vDG granule cell activity, leading to affective symptoms. Tryptophanase-producing microbiota transplantation, indole/tryptophanase supplementation, chemogenetic activation of vDG neurons, or diosmin, a clinically approved AhR agonist, rescued emotional symptoms in IBS mice. Together, these findings define an <em>Alistipes shahii</em>-tryptophanase-indole-AhR-vDG pathway as a mechanistic and translationally tractable gut-brain axis underlying affective disturbances.","PeriodicalId":9840,"journal":{"name":"Cell metabolism","volume":"12 1","pages":""},"PeriodicalIF":29.0,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147586726","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Cell metabolismPub Date : 2026-03-31DOI: 10.1016/j.cmet.2026.03.002
Cheng-Lin Lu, Jing Ren, Yueshiyuan Lei, Xiao-Ying Lian, Hao-Tian Jiang, Fang Guo, Liang-Yu Chen, Jia-Wen Mo, Hongyun Mao, Jun Fan, Guangyan Wu, Wan-Qian Ye, You-Lu Wen, Haitao Sun, Yan He, Jiubo Zhao, Xiong Cao
{"title":"The gut microbiota alleviates depression by remodeling gut-brain energy metabolism","authors":"Cheng-Lin Lu, Jing Ren, Yueshiyuan Lei, Xiao-Ying Lian, Hao-Tian Jiang, Fang Guo, Liang-Yu Chen, Jia-Wen Mo, Hongyun Mao, Jun Fan, Guangyan Wu, Wan-Qian Ye, You-Lu Wen, Haitao Sun, Yan He, Jiubo Zhao, Xiong Cao","doi":"10.1016/j.cmet.2026.03.002","DOIUrl":"https://doi.org/10.1016/j.cmet.2026.03.002","url":null,"abstract":"Although peripheral-brain crosstalk regulates energy metabolism, its role in depression remains unclear. Here, we used metabolic profiling to reveal elevated fecal creatine alongside reduced plasma and cerebrospinal fluid creatine in both patients with depression and mouse depression models. Exogenous creatine produced antidepressant-like effects mediated by gut microbiota. <em>Bifidobacterium pseudolongum</em> was identified as a significantly reduced gut bacterial species in depression, correlating with impaired creatine absorption. Subsequent supplementation with <em>Bifidobacterium</em> enhanced the antidepressant effects of creatine. Mechanistically, <em>B. pseudolongum</em>-derived acetate promoted the creatine transporter (<em>Slc6a8</em>) expression in intestinal epithelial cells via histone acetylation. The <em>Slc6a8</em> mediated the antidepressant-like effects of creatine. Neuronal creatine deficiency influenced energetic metabolism and neurophysiological function. In patients with depression taking antidepressants, co-administration of creatine and <em>Bifidobacterium</em> increased plasma creatine levels and reduced depression scores. These findings identify the <em>Bifidobacterium</em>-creatine combination as a promising antidepressant strategy and highlight the critical role of gut-brain energy metabolism in depression.","PeriodicalId":9840,"journal":{"name":"Cell metabolism","volume":"103 1","pages":""},"PeriodicalIF":29.0,"publicationDate":"2026-03-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147586418","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Cell metabolismPub Date : 2026-03-27DOI: 10.1016/j.cmet.2026.03.010
Filip J. Larsen
{"title":"Lactate-driven mitochondrial pretenders hijack hippocampal function after excessive exercise","authors":"Filip J. Larsen","doi":"10.1016/j.cmet.2026.03.010","DOIUrl":"https://doi.org/10.1016/j.cmet.2026.03.010","url":null,"abstract":"(Cell Metabolism <em>38</em>, 257–259; February 3, 2026)","PeriodicalId":9840,"journal":{"name":"Cell metabolism","volume":"18 1","pages":""},"PeriodicalIF":29.0,"publicationDate":"2026-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147536608","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Maltol induces diabetic fragility fractures by disrupting the balance of bone remodeling","authors":"Jinyang Wang, Ziyuan Wang, Jinyi Feng, Ying Zhang, Lizheng Yao, Yiran Zhang, Ruijie Zhang, Jingyi Cai, Hao Yu, Songhan Deng, Xinrui Chen, Rui Liang, Caoxin Huang, Jia Li, Xuejun Li, Qinxi Li, Xiulin Shi","doi":"10.1016/j.cmet.2026.03.001","DOIUrl":"https://doi.org/10.1016/j.cmet.2026.03.001","url":null,"abstract":"Type 2 diabetes is a major risk factor for fragility fractures, yet the contributors to skeletal fragility remain unclear. Through integrated clinical metabolomics, <em>in vivo</em>, and <em>in vitro</em> analyses, we identify maltol—a widely used food additive—as a previously unrecognized risk factor for hyperglycemia-associated bone fragility. Metabolomic profiling of femoral neck tissue from individuals with fragility fractures showed diabetes-associated maltol accumulation, and elevated circulating maltol levels correlated with increased fracture incidence. Mechanistically, maltol inhibits osteoblast differentiation via Wnt/β-catenin and promotes osteoclast maturation through nuclear factor κB (NF-κB) signaling, disrupting bone remodeling. These effects are amplified under hyperglycemia, while insulin reversal of glucose levels mitigates maltol-induced skeletal deterioration in mouse models. Given the widespread use of maltol in processed foods, these findings suggest that food additive safety should consider metabolic context and call for disease-specific dietary exposure guidelines to reduce fracture risk in diabetes.","PeriodicalId":9840,"journal":{"name":"Cell metabolism","volume":"15 1","pages":""},"PeriodicalIF":29.0,"publicationDate":"2026-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147518785","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Cell metabolismPub Date : 2026-03-24DOI: 10.1016/j.cmet.2026.03.009
Claire H. Feetham, Sam Groom, Linu M. John, Berit Ostergaard Christoffersen, Valeria Collabolletta, David Lyons, Antony Adamson, Sofia Lundh, Marina Kjærgaard Gerstenberg, Mads Tang-Christensen, Kilian W. Conde-Frieboes, Anna Secher, Ann Maria Kruse Hansen, Simon M. Luckman
{"title":"Analog of prolactin-releasing peptide reduces body weight primarily through sustained fatty acid oxidation rather than hypophagia","authors":"Claire H. Feetham, Sam Groom, Linu M. John, Berit Ostergaard Christoffersen, Valeria Collabolletta, David Lyons, Antony Adamson, Sofia Lundh, Marina Kjærgaard Gerstenberg, Mads Tang-Christensen, Kilian W. Conde-Frieboes, Anna Secher, Ann Maria Kruse Hansen, Simon M. Luckman","doi":"10.1016/j.cmet.2026.03.009","DOIUrl":"https://doi.org/10.1016/j.cmet.2026.03.009","url":null,"abstract":"","PeriodicalId":9840,"journal":{"name":"Cell metabolism","volume":"2 1","pages":""},"PeriodicalIF":29.0,"publicationDate":"2026-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147501746","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Cell metabolismPub Date : 2026-03-23DOI: 10.1016/j.cmet.2026.02.018
Herbert Tilg, Timon E. Adolph, Stefano Romeo, Rohit Loomba
{"title":"The many pathways driving liver inflammation in MASH","authors":"Herbert Tilg, Timon E. Adolph, Stefano Romeo, Rohit Loomba","doi":"10.1016/j.cmet.2026.02.018","DOIUrl":"https://doi.org/10.1016/j.cmet.2026.02.018","url":null,"abstract":"Metabolic dysfunction-associated steatotic liver disease (MASLD) is the most prevalent chronic liver disease worldwide, affecting one-third of the global population. Most patients exhibit simple steatosis, whereas up to 20% develop metabolic dysfunction-associated steatohepatitis (MASH), potentially culminating in liver cirrhosis and hepatocellular carcinoma. Diverse parallel mechanisms contribute to the development of MASH, which are fueled by hepatic lipotoxicity, intestinal dysbiosis, and pro-inflammatory diets shaping innate and adaptive immune responses. Moreover, adipose tissue is driving systemic inflammation in obesity, contributing to the inflammatory burden in obesity-related MASH. Polygenetic and multiomic risk scores identify distinct types of MASLD with dominant aggressive liver disease or extrahepatic cardiometabolic disease. Here, we review the complexity of multiple parallel inflammatory hits in MASH and delineate that most current MASH drugs exert pleiotropic metabolic and anti-inflammatory properties. These new therapies will change the clinical management of this disease in the near future.","PeriodicalId":9840,"journal":{"name":"Cell metabolism","volume":"13 1","pages":""},"PeriodicalIF":29.0,"publicationDate":"2026-03-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147496064","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Cell metabolismPub Date : 2026-03-23DOI: 10.1016/j.cmet.2026.02.016
Ayaka Sugiura, Katherine L. Beier, Channing Chi, Darren R. Heintzman, Xiang Ye, Melissa M. Wolf, Andrew R. Patterson, Jacqueline-Yvonne Cephus, Hanna S. Hong, Jeffrey M. Perera, Costas A. Lyssiotis, Dawn C. Newcomb, Jeffrey C. Rathmell
{"title":"Tissue and CD4 T cell subset dependence on the amino acid transporter SLC38A1","authors":"Ayaka Sugiura, Katherine L. Beier, Channing Chi, Darren R. Heintzman, Xiang Ye, Melissa M. Wolf, Andrew R. Patterson, Jacqueline-Yvonne Cephus, Hanna S. Hong, Jeffrey M. Perera, Costas A. Lyssiotis, Dawn C. Newcomb, Jeffrey C. Rathmell","doi":"10.1016/j.cmet.2026.02.016","DOIUrl":"https://doi.org/10.1016/j.cmet.2026.02.016","url":null,"abstract":"","PeriodicalId":9840,"journal":{"name":"Cell metabolism","volume":"71 1","pages":""},"PeriodicalIF":29.0,"publicationDate":"2026-03-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147501748","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Cell metabolismPub Date : 2026-03-23DOI: 10.1016/j.cmet.2026.02.017
Mark A. Febbraio, Bente Klarlund Pedersen
{"title":"Exercise as a therapeutic intervention for long-lasting and chronic diseases","authors":"Mark A. Febbraio, Bente Klarlund Pedersen","doi":"10.1016/j.cmet.2026.02.017","DOIUrl":"https://doi.org/10.1016/j.cmet.2026.02.017","url":null,"abstract":"In a little over 100 years, global life expectancy has increased by ∼60%. Paradoxically, it has been estimated that we now exercise five times less than we did 100 years ago. Despite a marked increase in life expectancy, the prevalence of non-contagious diseases (NCDs), otherwise known as “chronic lifestyle diseases,” such as cardiovascular disease, type 2 diabetes, cognitive diseases, and cancer, has increased. Here, we discuss the concept of “exercise as medicine” for the treatment of NCD and provide evidence for the direct mechanisms by which regular physical activity can either prevent the onset or slow the progression of these diseases.","PeriodicalId":9840,"journal":{"name":"Cell metabolism","volume":"92 1","pages":""},"PeriodicalIF":29.0,"publicationDate":"2026-03-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147496062","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Plasma proteomic signature of frailty in 50,506 adults","authors":"Xueqing Jia, Weijing Gao, Hampus Hagelin, Yanjie Zhao, Jingyun Zhang, Xingqi Cao, Liming Zhang, Youheng Wu, Lina Ma, Liangkai Chen, Liang Sun, Huan Guo, Cuntai Zhang, Juulia Jylhävä, Zixin Hu, Emiel O. Hoogendijk, Sara Hägg, Zuyun Liu","doi":"10.1016/j.cmet.2026.02.013","DOIUrl":"https://doi.org/10.1016/j.cmet.2026.02.013","url":null,"abstract":"Proteomics enables the systematic elucidation of biological mechanisms underlying frailty. Through a large proteome-wide association study of 2,911 plasma proteins from 50,506 UK Biobank participants, we identified 1,339 proteins significantly associated with frailty, highlighting collagen-containing extracellular matrix and vesicle lumen pathways. Replication in the TwinGene study confirmed partial but consistent associations. Mendelian randomization analyses identified five potentially causal proteins for frailty. Moreover, we developed a proteomic frailty score (PFS) that showed strong predictive performance for 199 incident diseases across 13 categories and broad responsiveness to 84 modifiable risk factors. Longitudinal analyses revealed accelerated PFS progression with advancing age and increasing baseline frailty severity. An online tool (<ce:inter-ref xlink:href=\"https://zipoa.shinyapps.io/frailty/\" xlink:type=\"simple\">https://zipoa.shinyapps.io/frailty/</ce:inter-ref>) was created for public PFS calculation. Finally, we observed a biphasic pattern of frailty-associated proteomic dysregulation across the lifespan, with peaks at ages ∼50 and ∼63. Together, we establish PFS as a biomarker of biological aging while identifying critical windows and molecular targets for frailty interventions.","PeriodicalId":9840,"journal":{"name":"Cell metabolism","volume":"21 1","pages":""},"PeriodicalIF":29.0,"publicationDate":"2026-03-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147465716","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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