Cell metabolism最新文献_第4页

On the causes of obesity and its treatment: The end of the beginning 关于肥胖症的原因及其治疗：起点的终点

IF 29 1区生物学

Cell metabolism Pub Date : 2025-03-04 DOI: 10.1016/j.cmet.2025.01.026

Jeffrey M. Friedman

引用次数: 0

Decoding the complex systems of obesity 解码肥胖症的复杂系统

IF 29 1区生物学

Cell metabolism Pub Date : 2025-03-04 DOI: 10.1016/j.cmet.2025.02.001

Allyson Evans

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Famsin and fasting adaptation: A glucagon connection 饥饿素和禁食适应：胰高血糖素的联系

IF 29 1区生物学

Cell metabolism Pub Date : 2025-03-04 DOI: 10.1016/j.cmet.2025.01.030

Siming Li, Ziyi Meng, Jiandie D. Lin

引用次数: 0

SnapShot: Brain-targeting anti-obesity medications 快照：针对大脑的抗肥胖药物

IF 29 1区生物学

Cell metabolism Pub Date : 2025-03-04 DOI: 10.1016/j.cmet.2025.02.006

Jonas Petersen, Valdemar Brimnes Ingemann Johansen, Christoffer Clemmensen

引用次数: 0

Hepatic stellate cells regulate liver fatty acid utilization via plasmalemma vesicle-associated protein 肝星状细胞通过质膜囊泡相关蛋白调节肝脏对脂肪酸的利用

IF 29 1区生物学

Cell metabolism Pub Date : 2025-03-03 DOI: 10.1016/j.cmet.2025.01.022

Daniel Hansen, Jasmin E.R. Jensen, Christian A.T. Andersen, Peter R. Jakobsgaard, Jesper Havelund, Line Lauritsen, Samuel Mandacaru, Majken Siersbaek, Oliver L. Shackleton, Hiroshi Inoue, Jonathan R. Brewer, Robert F. Schwabe, Blagoy Blagoev, Nils J. Færgeman, Marko Salmi, Kim Ravnskjaer

{"title":"Hepatic stellate cells regulate liver fatty acid utilization via plasmalemma vesicle-associated protein","authors":"Daniel Hansen, Jasmin E.R. Jensen, Christian A.T. Andersen, Peter R. Jakobsgaard, Jesper Havelund, Line Lauritsen, Samuel Mandacaru, Majken Siersbaek, Oliver L. Shackleton, Hiroshi Inoue, Jonathan R. Brewer, Robert F. Schwabe, Blagoy Blagoev, Nils J. Færgeman, Marko Salmi, Kim Ravnskjaer","doi":"10.1016/j.cmet.2025.01.022","DOIUrl":"https://doi.org/10.1016/j.cmet.2025.01.022","url":null,"abstract":"The liver is essential for normal fatty acid utilization during fasting. Circulating fatty acids are taken up by hepatocytes and esterified as triacylglycerols for either oxidative metabolization and ketogenesis or export. Whereas the regulation of fatty acid oxidation in hepatocytes is well understood, the uptake and retention of non-esterified fatty acids by hepatocytes is not. Here, we show that murine hepatic stellate cells (HSCs) and their abundantly expressed plasmalemma vesicle-associated protein (PLVAP) control hepatic substrate preference for fasting energy metabolism. HSC-specific ablation of PLVAP in mice elevated hepatic insulin signaling and improved glucose tolerance. Fasted HSC PLVAP knockout mice showed suppressed hepatic fatty acid esterification into di- and triacylglycerols, shifting fasting metabolism from fatty acid oxidation to reliance on carbohydrates. By super-resolution microscopy, we localized HSC PLVAP to caveolae residing along the sinusoidal lumen, supporting a role for HSCs and PLVAP-diaphragmed caveolae in normal fasting metabolism of the liver.","PeriodicalId":9840,"journal":{"name":"Cell metabolism","volume":"84 1","pages":""},"PeriodicalIF":29.0,"publicationDate":"2025-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143532301","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

Pathogen-derived glyoxylate inhibits Tet2 DNA dioxygenase to facilitate bacterial persister formation 病原体衍生的乙醛酸抑制 Tet2 DNA 二氧酶，从而促进细菌宿主的形成

IF 29 1区生物学

Cell metabolism Pub Date : 2025-03-03 DOI: 10.1016/j.cmet.2025.01.019

Zhou-Li Cheng, Shuyuan Zhang, Zhenning Wang, Aixia Song, Chao Gao, Jun-Bin Song, Pu Wang, Lei Zhang, Yue Zhou, Wenyan Shan, Chen Zhang, Jinye Zhang, Yiping Sun, Yanhui Xu, Fei Lan, Ming Zhong, Liang-Dong Lyu, Guanghua Huang, Fei Xavier Chen, Gang Li, Dan Ye

{"title":"Pathogen-derived glyoxylate inhibits Tet2 DNA dioxygenase to facilitate bacterial persister formation","authors":"Zhou-Li Cheng, Shuyuan Zhang, Zhenning Wang, Aixia Song, Chao Gao, Jun-Bin Song, Pu Wang, Lei Zhang, Yue Zhou, Wenyan Shan, Chen Zhang, Jinye Zhang, Yiping Sun, Yanhui Xu, Fei Lan, Ming Zhong, Liang-Dong Lyu, Guanghua Huang, Fei Xavier Chen, Gang Li, Dan Ye","doi":"10.1016/j.cmet.2025.01.019","DOIUrl":"https://doi.org/10.1016/j.cmet.2025.01.019","url":null,"abstract":"Pathogenic bacterial persistence enables survival during antibiotic treatment, leading to treatment failure and recurrent infections, yet its underlying mechanisms remain unclear. Here, we reveal that glyoxylate, a metabolite originally evolved for alternative carbon utilization, functions as a signaling molecule to reprogram the host transcriptome and promote persister formation. Glyoxylate inhibits the DNA dioxygenase TET2, suppressing pro-inflammatory gene expression and attenuating host immune defense. Notably, stimulating TET2 activity with vitamin C or blocking glyoxylate production by <em>Salmonella</em> reduces bacterial antibiotic resistance and improves infection treatment outcomes. Beyond its metabolic role, glyoxylate emerges as a regulator of host-pathogen interactions, while TET2 plays a critical role in preventing bacterial persistence. Our findings suggest that targeting glyoxylate production or enhancing TET2 activity offers promising therapeutic strategies to combat bacterial persistence and enhance the efficacy of antibiotic treatments.","PeriodicalId":9840,"journal":{"name":"Cell metabolism","volume":"37 1","pages":""},"PeriodicalIF":29.0,"publicationDate":"2025-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143532286","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

Realigned transsulfuration drives BRAF-V600E-targeted therapy resistance in melanoma 重组转硫驱动braf - v600e靶向治疗在黑色素瘤中的耐药性

IF 29 1区生物学

Cell metabolism Pub Date : 2025-03-03 DOI: 10.1016/j.cmet.2025.01.021

Klaudia Borbényi-Galambos, Katalin Erdélyi, Tamás Ditrói, Eszter Petra Jurányi, Noémi Szántó, Réka Szatmári, Ágnes Czikora, Edward E. Schmidt, Dorottya Garai, Mihály Cserepes, Gabriella Liszkay, Erika Tóth, József Tóvári, Péter Nagy

{"title":"Realigned transsulfuration drives BRAF-V600E-targeted therapy resistance in melanoma","authors":"Klaudia Borbényi-Galambos, Katalin Erdélyi, Tamás Ditrói, Eszter Petra Jurányi, Noémi Szántó, Réka Szatmári, Ágnes Czikora, Edward E. Schmidt, Dorottya Garai, Mihály Cserepes, Gabriella Liszkay, Erika Tóth, József Tóvári, Péter Nagy","doi":"10.1016/j.cmet.2025.01.021","DOIUrl":"https://doi.org/10.1016/j.cmet.2025.01.021","url":null,"abstract":"BRAF V600E-inhibition effectively treats melanoma, but acquired resistance rapidly develops. Protein expression profiles, mitochondrial energetics, metabolomics and fluxomics data in cell line, xenograft, and patient-derived xenograft systems revealed that concerted reprogramming of metabolic pathways (including glutaminolysis, glycolysis, TCA cycle, electron transport chain [ETC], and transsulfuration), along with an immediate cytoprotective response to drug-induced oxidative stress, underpins drug-tolerant persister cancer cell survival. Realignment of cysteine (Cys) metabolism, in particular an immediate upregulation of cystathionine-γ-lyase (CSE), was vital in persister cells. The oxidative cellular environment, drug-induced elevated cystine uptake and oxidative Cys catabolism, increased intracellular cystine/Cys ratios, thereby favoring cystine as a CSE substrate. This produces persulfides and hydrogen sulfide to protect protein thiols and support elevated energy demand in persister cells. Combining BRAF V600E inhibitors with CSE inhibitors effectively diminished proliferative relapse in culture models and increased progression-free survival of xenografted mice. This, together with induced CSE expression in patient samples under BRAF-V600E-inhibition, reveals an approach to increase BRAF-V600E-targeted therapeutic efficacy.","PeriodicalId":9840,"journal":{"name":"Cell metabolism","volume":"34 1","pages":""},"PeriodicalIF":29.0,"publicationDate":"2025-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143532400","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

MIF-ACKR3 causes irreversible fat loss by impairing adipogenesis in cancer cachexia MIF-ACKR3通过损害癌症恶病质中的脂肪生成导致不可逆的脂肪减少

IF 29 1区生物学

Cell metabolism Pub Date : 2025-02-27 DOI: 10.1016/j.cmet.2025.01.018

Qionghua Cui, Shijin Li, Xidan Liu, Jie Liu, Wenxin Chen, Ye Sheng, Peng Xie, Li Jin, Fanxin Zeng, Fengxiang Lv, Xinli Hu, Rui-Ping Xiao

引用次数: 0

Hepatic sphingomyelin phosphodiesterase 3 promotes steatohepatitis by disrupting membrane sphingolipid metabolism 肝鞘磷脂磷酸二酯酶3通过破坏鞘脂膜代谢促进脂肪性肝炎

IF 29 1区生物学

Cell metabolism Pub Date : 2025-02-26 DOI: 10.1016/j.cmet.2025.01.016

Jie Jiang, Yuqing Gao, Jiang Wang, Yan Huang, Rong Yang, Yongxin Zhang, Yuandi Ma, Yingquan Wen, Gongkai Luo, Shurui Zhang, Yutang Cao, Minjun Yu, Qinxue Wang, Shulei Hu, Kanglong Wang, Xiaozhen Guo, Frank J. Gonzalez, Yameng Liu, Hong Liu, Qing Xie, Cen Xie

{"title":"Hepatic sphingomyelin phosphodiesterase 3 promotes steatohepatitis by disrupting membrane sphingolipid metabolism","authors":"Jie Jiang, Yuqing Gao, Jiang Wang, Yan Huang, Rong Yang, Yongxin Zhang, Yuandi Ma, Yingquan Wen, Gongkai Luo, Shurui Zhang, Yutang Cao, Minjun Yu, Qinxue Wang, Shulei Hu, Kanglong Wang, Xiaozhen Guo, Frank J. Gonzalez, Yameng Liu, Hong Liu, Qing Xie, Cen Xie","doi":"10.1016/j.cmet.2025.01.016","DOIUrl":"https://doi.org/10.1016/j.cmet.2025.01.016","url":null,"abstract":"Metabolic-dysfunction-associated steatohepatitis (MASH) remains a major health challenge. Herein, we identify sphingomyelin phosphodiesterase 3 (SMPD3) as a key driver of hepatic ceramide accumulation through increasing sphingomyelin hydrolysis at the cell membrane. Hepatocyte-specific <em>Smpd3</em> gene disruption or pharmacological inhibition of SMPD3 alleviates MASH, whereas reintroducing SMPD3 reverses the resolution of MASH. Although healthy livers express low-level SMPD3, lipotoxicity-induced DNA damage suppresses sirtuin 1 (SIRT1), triggering an upregulation of SMPD3 during MASH. This disrupts membrane sphingomyelin-ceramide balance and promotes disease progression by enhancing caveolae-dependent lipid uptake and extracellular vesicle secretion from steatotic hepatocytes to exacerbate inflammation and fibrosis. Consequently, SMPD3 acts as a central hub integrating key MASH hallmarks. Notably, we discovered a bifunctional agent that simultaneously activates SIRT1 and inhibits SMPD3, which shows significant therapeutic potential in MASH treatment. These findings suggest that inhibition of hepatic SMPD3 restores membrane sphingolipid metabolism and holds great promise for developing novel MASH therapies.","PeriodicalId":9840,"journal":{"name":"Cell metabolism","volume":"24 1","pages":""},"PeriodicalIF":29.0,"publicationDate":"2025-02-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143495774","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

EHBP1 suppresses liver fibrosis in metabolic dysfunction-associated steatohepatitis EHBP1抑制代谢功能障碍相关脂肪性肝炎的肝纤维化

IF 29 1区生物学

Cell metabolism Pub Date : 2025-02-26 DOI: 10.1016/j.cmet.2025.01.020

Fanglin Ma, Miriam Longo, Marica Meroni, Dipankar Bhattacharya, Erika Paolini, Shama Mughal, Syed Hussain, Sumit Kumar Anand, Neha Gupta, Yiwei Zhu, Amaia Navarro-Corcuera, Kenneth Li, Satya Prakash, Bruno Cogliati, Shuang Wang, Xin Huang, Xiaobo Wang, Arif Yurdagul, Oren Rom, Liheng Wang, Bishuang Cai

{"title":"EHBP1 suppresses liver fibrosis in metabolic dysfunction-associated steatohepatitis","authors":"Fanglin Ma, Miriam Longo, Marica Meroni, Dipankar Bhattacharya, Erika Paolini, Shama Mughal, Syed Hussain, Sumit Kumar Anand, Neha Gupta, Yiwei Zhu, Amaia Navarro-Corcuera, Kenneth Li, Satya Prakash, Bruno Cogliati, Shuang Wang, Xin Huang, Xiaobo Wang, Arif Yurdagul, Oren Rom, Liheng Wang, Bishuang Cai","doi":"10.1016/j.cmet.2025.01.020","DOIUrl":"https://doi.org/10.1016/j.cmet.2025.01.020","url":null,"abstract":"Excess cholesterol accumulation contributes to fibrogenesis in metabolic dysfunction-associated steatohepatitis (MASH), but how hepatic cholesterol metabolism becomes dysregulated in MASH is not completely understood. We show that human fibrotic MASH livers have decreased EH-domain-binding protein 1 (EHBP1), a genome-wide association study (GWAS) locus associated with low-density lipoprotein (LDL) cholesterol, and that EHBP1 loss- and gain-of-function increase and decrease MASH fibrosis in mice, respectively. Mechanistic studies reveal that EHBP1 promotes sortilin-mediated PCSK9 secretion, leading to LDL receptor (LDLR) degradation, decreased LDL uptake, and reduced TAZ, a fibrogenic effector. At a cellular level, EHBP1 deficiency affects the intracellular localization of retromer, a protein complex required for sortilin stabilization. Our therapeutic approach to stabilizing retromer is effective in mitigating MASH fibrosis. Moreover, we show that the tumor necrosis factor alpha (TNF-α)/peroxisome proliferator-activated receptor alpha (PPARα) pathway suppresses EHBP1 in MASH. These data not only provide mechanistic insights into the role of EHBP1 in cholesterol metabolism and MASH fibrosis but also elucidate an interplay between inflammation and EHBP1-mediated cholesterol metabolism.","PeriodicalId":9840,"journal":{"name":"Cell metabolism","volume":"27 1","pages":""},"PeriodicalIF":29.0,"publicationDate":"2025-02-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143495773","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