Cell metabolism最新文献

Acetylated cellulose suppresses body mass gain through gut commensals consuming host-accessible carbohydrates 乙酰化纤维素通过肠道共生体消耗宿主可获得的碳水化合物来抑制体重增加

IF 29 1区生物学

Cell metabolism Pub Date : 2025-05-16 DOI: 10.1016/j.cmet.2025.04.013

Tadashi Takeuchi, Eiji Miyauchi, Yumiko Nakanishi, Yusuke Ito, Tamotsu Kato, Katsuki Yaguchi, Masami Kawasumi, Naoko Tachibana, Ayumi Ito, Shu Shimamoto, Akinobu Matsuyama, Nobuo Sasaki, Ikuo Kimura, Hiroshi Ohno

{"title":"Acetylated cellulose suppresses body mass gain through gut commensals consuming host-accessible carbohydrates","authors":"Tadashi Takeuchi, Eiji Miyauchi, Yumiko Nakanishi, Yusuke Ito, Tamotsu Kato, Katsuki Yaguchi, Masami Kawasumi, Naoko Tachibana, Ayumi Ito, Shu Shimamoto, Akinobu Matsuyama, Nobuo Sasaki, Ikuo Kimura, Hiroshi Ohno","doi":"10.1016/j.cmet.2025.04.013","DOIUrl":"https://doi.org/10.1016/j.cmet.2025.04.013","url":null,"abstract":"Effective approaches to preventing and treating obesity are urgently needed. Although current strategies primarily focus on direct modulation of host metabolism, another promising approach may involve limiting nutrient availability through regulation of the gut microbiota, which links diet and host physiology. Here, we report that acetylated cellulose (AceCel), which markedly alters gut bacterial composition and function, reduces body mass gain in both wild-type and obese mice. AceCel limits carbohydrate oxidation and promotes fatty acid oxidation in the host liver in a microbiota-dependent manner. We further show that acetate enhances carbohydrate fermentation by the gut commensal Bacteroides thetaiotaomicron, depleting host-accessible simple sugars in the gut of AceCel-fed mice. These findings highlight the potential of AceCel as a prebiotic that regulates carbohydrate metabolism in both bacteria and host, offering promise as a therapeutic strategy for obesity.","PeriodicalId":9840,"journal":{"name":"Cell metabolism","volume":"33 1","pages":""},"PeriodicalIF":29.0,"publicationDate":"2025-05-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144066028","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

Hydrogen peroxide in midbrain sleep neurons regulates sleep homeostasis 中脑睡眠神经元中的过氧化氢调节睡眠稳态

IF 29 1区生物学

Cell metabolism Pub Date : 2025-05-15 DOI: 10.1016/j.cmet.2025.04.016

Yujing Tian, Luwei Kang, Ngoc T. Ha, Juan Deng, Danqian Liu

{"title":"Hydrogen peroxide in midbrain sleep neurons regulates sleep homeostasis","authors":"Yujing Tian, Luwei Kang, Ngoc T. Ha, Juan Deng, Danqian Liu","doi":"10.1016/j.cmet.2025.04.016","DOIUrl":"https://doi.org/10.1016/j.cmet.2025.04.016","url":null,"abstract":"Sleep could protect animals from oxidative damage, yet the dynamic interplay between the redox state and sleep homeostasis remains unclear. Here, we show that acute sleep deprivation (SD) in mice caused a general increase in brain oxidation, particularly in sleep-promoting regions. In vivo imaging of intracellular hydrogen peroxide (H2O2) real-time dynamics revealed that in nigra sleep neurons, the increase in cytosolic but not mitochondrial H2O2 reflects sleep debt and tracks spontaneous wakefulness by positively correlating with wake duration. By controllably manipulating intraneuronal H2O2, we discovered that H2O2 elevation is required for compensatory sleep and causally promotes sleep initiation, at least partly dependent on transient receptor potential melastatin 2 (TRPM2) channel. However, excessive H2O2 induced brain inflammation and sleep fragmentation. Together, our study demonstrates intraneuronal H2O2 as a crucial signaling molecule that translates brain redox imbalance into sleep drive and underscores the significance of oxidative eustress in sleep homeostasis.","PeriodicalId":9840,"journal":{"name":"Cell metabolism","volume":"40 1","pages":""},"PeriodicalIF":29.0,"publicationDate":"2025-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143980017","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

Hepatic lipid remodeling in cold exposure uncovers direct regulation of bis(monoacylglycero)phosphate lipids by phospholipase A2 group XV 低温暴露时肝脏脂质重塑揭示了磷脂酶A2组XV对单酰基甘油磷酸脂的直接调节

IF 29 1区生物学

Cell metabolism Pub Date : 2025-05-14 DOI: 10.1016/j.cmet.2025.04.015

Jessica W. Davidson, Raghav Jain, Thomas Kizzar, Gisela Geoghegan, Daniel J. Nesbitt, Amy Cavanagh, Akira Abe, Kwamina Nyame, Andrea Hunger, Xiaojuan Chao, Isabella James, Helaina Walesewicz, Dominique A. Baldwin, Gina Wade, Sylwia Michorowska, Rakesh Verma, Kathryn Schueler, Vania Hinkovska-Galcheva, Evgenia Shishkova, Wen-Xing Ding, Judith A. Simcox

{"title":"Hepatic lipid remodeling in cold exposure uncovers direct regulation of bis(monoacylglycero)phosphate lipids by phospholipase A2 group XV","authors":"Jessica W. Davidson, Raghav Jain, Thomas Kizzar, Gisela Geoghegan, Daniel J. Nesbitt, Amy Cavanagh, Akira Abe, Kwamina Nyame, Andrea Hunger, Xiaojuan Chao, Isabella James, Helaina Walesewicz, Dominique A. Baldwin, Gina Wade, Sylwia Michorowska, Rakesh Verma, Kathryn Schueler, Vania Hinkovska-Galcheva, Evgenia Shishkova, Wen-Xing Ding, Judith A. Simcox","doi":"10.1016/j.cmet.2025.04.015","DOIUrl":"https://doi.org/10.1016/j.cmet.2025.04.015","url":null,"abstract":"Cold exposure is a selective environmental stress that elicits a rapid metabolic shift to maintain energy homeostasis. In response to cold exposure, the liver rewires the metabolic state, shifting from glucose to lipid catabolism. By probing the liver lipids in cold exposure, we observed that the lysosomal bis(monoacylglycero)phosphate (BMP) lipids were rapidly increased during cold exposure. BMP lipid changes occurred independently of lysosomal abundance but were dependent on the lysosomal transcriptional regulator transcription factor EB (TFEB). Knockdown of Tfeb in hepatocytes decreased BMP lipid levels and led to cold intolerance in mice. We assessed TFEB-binding sites of lysosomal genes and determined that the phospholipase a2 group XV (PLA2G15) regulates BMP lipid catabolism. Decreasing Pla2g15 levels in mice increased BMP lipids, ablated the cold-induced rise in BMP lipids, and improved cold tolerance. Mutation of the catalytic site of PLA2G15 ablated the BMP lipid breakdown. Together, our studies uncover TFEB regulation of BMP lipids through PLA2G15 catabolism.","PeriodicalId":9840,"journal":{"name":"Cell metabolism","volume":"39 1","pages":""},"PeriodicalIF":29.0,"publicationDate":"2025-05-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143946252","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

FGF21 reverses MASH through coordinated actions on the CNS and liver FGF21通过对中枢神经系统和肝脏的协同作用逆转MASH

IF 29 1区生物学

Cell metabolism Pub Date : 2025-05-13 DOI: 10.1016/j.cmet.2025.04.014

Jesse P. Rose, Donald A. Morgan, Andrew I. Sullivan, Xiaorong Fu, Melissa Inigo-Vollmer, Shawn C. Burgess, David K. Meyerholz, Kamal Rahmouni, Matthew J. Potthoff

{"title":"FGF21 reverses MASH through coordinated actions on the CNS and liver","authors":"Jesse P. Rose, Donald A. Morgan, Andrew I. Sullivan, Xiaorong Fu, Melissa Inigo-Vollmer, Shawn C. Burgess, David K. Meyerholz, Kamal Rahmouni, Matthew J. Potthoff","doi":"10.1016/j.cmet.2025.04.014","DOIUrl":"https://doi.org/10.1016/j.cmet.2025.04.014","url":null,"abstract":"Metabolic dysfunction-associated steatotic liver disease (MASLD) and its progressive form, metabolic dysfunction-associated steatohepatitis (MASH), represent a growing public health burden with limited therapeutic options. Recent studies have revealed that fibroblast growth factor 21 (FGF21)-based analogs can significantly improve MASH, but the mechanisms for this effect are not well understood. Here, we demonstrate that the beneficial metabolic effects of FGF21 to reverse MASH are mediated through distinct mechanisms to independently lower hepatic triglyceride and cholesterol levels. Specifically, FGF21 signaling directly to glutamatergic neurons in the central nervous system (CNS) stimulates hepatic triglyceride reduction and reversal of fibrosis, whereas FGF21 signaling directly to hepatocytes is necessary and sufficient to reduce hepatic cholesterol levels in mice. Mechanistically, we show that FGF21 acts in the CNS to increase sympathetic nerve activity to the liver, which suppresses hepatic de novo lipogenesis. These results provide critical insights into a promising pharmacological target to treat MASH.","PeriodicalId":9840,"journal":{"name":"Cell metabolism","volume":"41 1","pages":""},"PeriodicalIF":29.0,"publicationDate":"2025-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143940143","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 foam cell-derived exosomes exacerbate ischemic white matter injury via transmitting metabolic defects to microglia 泡沫细胞衍生的外泌体通过将代谢缺陷传递给小胶质细胞而加剧缺血性白质损伤

IF 29 1区生物学

Cell metabolism Pub Date : 2025-05-08 DOI: 10.1016/j.cmet.2025.04.009

Hang Zhang, Luo-Qi Zhou, Sheng Yang, Ming-Hao Dong, Lian Chen, Yi-Lin Lu, Lu-Yang Zhang, Lan Zhang, Yun-Hui Chu, Lu-Lu Xu, Xiao-Wei Pang, Li-Fang Zhu, Ting Xu, Tu-ying Yong, Wei Wang, Dai-Shi Tian, Chuan Qin

引用次数: 0

Endoplasmic reticulum Nogo drives AgRP neuronal activation and feeding behavior 内质网Nogo驱动AgRP神经元的激活和摄食行为

IF 29 1区生物学

Cell metabolism Pub Date : 2025-05-06 DOI: 10.1016/j.cmet.2025.04.005

Sungho Jin, Nal Ae Yoon, Mian Wei, Tilla Worgall, Luisa Rubinelli, Tamas L. Horvath, Wei Min, Nadia Diano, Annarita di Lorenzo, Sabrina Diano

{"title":"Endoplasmic reticulum Nogo drives AgRP neuronal activation and feeding behavior","authors":"Sungho Jin, Nal Ae Yoon, Mian Wei, Tilla Worgall, Luisa Rubinelli, Tamas L. Horvath, Wei Min, Nadia Diano, Annarita di Lorenzo, Sabrina Diano","doi":"10.1016/j.cmet.2025.04.005","DOIUrl":"https://doi.org/10.1016/j.cmet.2025.04.005","url":null,"abstract":"Lipid sensing in the hypothalamus contributes to the control of feeding and whole-body metabolism. However, the mechanism responsible for this nutrient-sensing process is ill-defined. Here, we show that Nogo-A, encoded by reticulon 4 (Rtn4) gene and associated with brain development and synaptic plasticity, regulates feeding and energy metabolism by controlling lipid metabolism in Agouti-related protein (AgRP) neurons. Nogo-A expression was upregulated in AgRP neurons of fasted mice and was associated with a significant downregulation of enzymes involved in sphingolipid de novo biosynthesis and the upregulation of key enzymes in intracellular lipid transport and fatty acid oxidation. Deletion of Rtn4 in AgRP neurons reduced body weight, ghrelin-induced AgRP activity and food intake, and fasting-induced AgRP activation, together with an increase in ceramide levels. Finally, high-fat-diet-induced obesity induced a significant downregulation of Rtn4 and increased ceramide levels in AgRP neurons, suggesting a role for Nogo in AgRP dysregulation in obesity. Taken together, our data reveal that Nogo-A drives AgRP neuronal activity and associated feeding behavior by controlling mitochondrial function and cellular lipid metabolism.","PeriodicalId":9840,"journal":{"name":"Cell metabolism","volume":"115 1","pages":""},"PeriodicalIF":29.0,"publicationDate":"2025-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143910628","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

Cell Metabolism 20th anniversary Voices: Part 2 of 3 细胞代谢20周年纪念声音：三集之二

IF 29 1区生物学

Cell metabolism Pub Date : 2025-05-06 DOI: 10.1016/j.cmet.2025.04.004

Shingo Kajimura, Cristina García-Cáceres, Lawrence Kazak, Edward B. Thorp, Katrin J. Svensson, Ling Yang

引用次数: 0

Does sweet turn sour? How aspartame aggravates atherosclerosis in a preclinical model 甜的会变酸吗？阿斯巴甜如何在临床前模型中加重动脉粥样硬化

IF 29 1区生物学

Cell metabolism Pub Date : 2025-05-06 DOI: 10.1016/j.cmet.2025.04.003

M. Yanina Pepino, Jaume Amengual

引用次数: 0

Bacteria-derived nutrient recycling: How phagocytosed bacteria regulate macrophage metabolism 细菌衍生的营养循环：被吞噬的细菌如何调节巨噬细胞代谢

IF 29 1区生物学

Cell metabolism Pub Date : 2025-05-06 DOI: 10.1016/j.cmet.2025.03.018

Andrea Riviello, Dirk Brenner

引用次数: 0

Foxp3 confers long-term efficacy of chimeric antigen receptor-T cells via metabolic reprogramming Foxp3通过代谢重编程赋予嵌合抗原受体-t细胞的长期功效

IF 29 1区生物学

Cell metabolism Pub Date : 2025-05-05 DOI: 10.1016/j.cmet.2025.04.008

Congyi Niu, Huan Wei, Xuanxuan Pan, Yuedi Wang, Huan Song, Congwen Li, Jingbo Qie, Jiawen Qian, Shaocong Mo, Wanwei Zheng, Kameina Zhuma, Zixin Lv, Yiyuan Gao, Dan Zhang, Hui Yang, Ronghua Liu, Luman Wang, Wenwei Tu, Jie Liu, Yiwei Chu, Feifei Luo

{"title":"Foxp3 confers long-term efficacy of chimeric antigen receptor-T cells via metabolic reprogramming","authors":"Congyi Niu, Huan Wei, Xuanxuan Pan, Yuedi Wang, Huan Song, Congwen Li, Jingbo Qie, Jiawen Qian, Shaocong Mo, Wanwei Zheng, Kameina Zhuma, Zixin Lv, Yiyuan Gao, Dan Zhang, Hui Yang, Ronghua Liu, Luman Wang, Wenwei Tu, Jie Liu, Yiwei Chu, Feifei Luo","doi":"10.1016/j.cmet.2025.04.008","DOIUrl":"https://doi.org/10.1016/j.cmet.2025.04.008","url":null,"abstract":"The tumor microenvironment, characterized by low oxygen tension and scarce nutrients, impairs chimeric antigen receptor (CAR)-T cell metabolism, leading to T cell exhaustion and dysfunction. Notably, Foxp3 confers a metabolic advantage to regulatory T cells under such restrictive conditions. Exploiting this property, we generated CAR-TFoxp3 cells by co-expressing Foxp3 with a third-generation CAR construct. The CAR-TFoxp3 cells exhibited distinct metabolic reprogramming, marked by downregulated aerobic glycolysis and oxidative phosphorylation coupled with upregulated lipid metabolism. This metabolic shift was driven by Foxp3’s interaction with dynamin-related protein 1. Crucially, CAR-TFoxp3 cells did not acquire regulatory T cell immunosuppressive functions but instead demonstrated enhanced antitumor potency and reduced expression of exhaustion markers via Foxp3-mediated adaptation. The potent antitumor effect and absence of immunosuppression were confirmed in a humanized immune system mouse model. Our findings establish a metabolic reprogramming-based strategy to enhance CAR-T cell adaptability within the hostile tumor microenvironment while preserving therapeutic efficacy.","PeriodicalId":9840,"journal":{"name":"Cell metabolism","volume":"17 1","pages":""},"PeriodicalIF":29.0,"publicationDate":"2025-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143905435","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