Cell metabolism最新文献_第3页

Tirzepatide did not impact metabolic adaptation in people with obesity, but increased fat oxidation 替西帕肽不会影响肥胖人群的代谢适应，但会增加脂肪氧化

IF 29 1区生物学

Cell metabolism Pub Date : 2025-04-08 DOI: 10.1016/j.cmet.2025.03.011

Eric Ravussin, Guillermo Sanchez-Delgado, Corby K. Martin, Robbie A. Beyl, Frank L. Greenway, Libbey S. O’Farrell, William C. Roell, Hui-Rong Qian, Jing Li, Hiroshi Nishiyama, Axel Haupt, Edward J. Pratt, Shweta Urva, Zvonko Milicevic, Tamer Coskun

{"title":"Tirzepatide did not impact metabolic adaptation in people with obesity, but increased fat oxidation","authors":"Eric Ravussin, Guillermo Sanchez-Delgado, Corby K. Martin, Robbie A. Beyl, Frank L. Greenway, Libbey S. O’Farrell, William C. Roell, Hui-Rong Qian, Jing Li, Hiroshi Nishiyama, Axel Haupt, Edward J. Pratt, Shweta Urva, Zvonko Milicevic, Tamer Coskun","doi":"10.1016/j.cmet.2025.03.011","DOIUrl":"https://doi.org/10.1016/j.cmet.2025.03.011","url":null,"abstract":"Tirzepatide, a glucose-dependent insulinotropic polypeptide and glucagon-like peptide-1 receptor agonist, promoted significant body weight reduction in the phase 3 clinical trials. We conducted a preclinical study and a phase 1 clinical trial (NCT04081337) to understand potential mechanisms mediating tirzepatide-induced weight loss in mice and people with obesity. In calorie-restricted, obese mice, chronic treatment with tirzepatide reduced the drop in energy expenditure that occurred in vehicle-treated and pair-fed mice, indicating that tirzepatide attenuated metabolic adaptation. Respiratory exchange ratio also decreased in tirzepatide-treated mice, indicating increased fat oxidation. In the clinical trial, tirzepatide appeared to have no impact on metabolic adaptation but led to increased fat oxidation and reductions in appetite and calorie intake during an ad libitum test meal (vs. placebo). This is the first study to provide insights into the mechanisms of action of tirzepatide on weight loss with respect to calorie intake, energy expenditure, and macronutrient utilization.","PeriodicalId":9840,"journal":{"name":"Cell metabolism","volume":"18 1","pages":""},"PeriodicalIF":29.0,"publicationDate":"2025-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143798388","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

Identification of a molecular resistor that controls UCP1-independent Ca2+ cycling thermogenesis in adipose tissue 脂肪组织中控制ucp1独立的Ca2+循环产热的分子电阻的鉴定

IF 29 1区生物学

Cell metabolism Pub Date : 2025-04-07 DOI: 10.1016/j.cmet.2025.03.009

Christopher Auger, Mark Li, Masanori Fujimoto, Kenji Ikeda, Jin-Seon Yook, Timothy R. O’Leary, María Paula Huertas Caycedo, Cai Xiaohan, Satoshi Oikawa, Anthony R.P. Verkerke, Kosaku Shinoda, Patrick R. Griffin, Kenji Inaba, Roland H. Stimson, Shingo Kajimura

{"title":"Identification of a molecular resistor that controls UCP1-independent Ca2+ cycling thermogenesis in adipose tissue","authors":"Christopher Auger, Mark Li, Masanori Fujimoto, Kenji Ikeda, Jin-Seon Yook, Timothy R. O’Leary, María Paula Huertas Caycedo, Cai Xiaohan, Satoshi Oikawa, Anthony R.P. Verkerke, Kosaku Shinoda, Patrick R. Griffin, Kenji Inaba, Roland H. Stimson, Shingo Kajimura","doi":"10.1016/j.cmet.2025.03.009","DOIUrl":"https://doi.org/10.1016/j.cmet.2025.03.009","url":null,"abstract":"Adipose tissue thermogenesis contributes to energy balance via mitochondrial uncoupling protein 1 (UCP1) and UCP1-independent pathways. Among UCP1-independent thermogenic mechanisms, one involves Ca2+ cycling via SERCA2b in adipose tissue; however, the underlying molecular basis remains elusive. Here, we report that an endoplasmic reticulum (ER) membrane-anchored peptide, C4orf3 (also known as another regulin [ALN]), uncouples SERCA2b Ca2+ transport from its ATP hydrolysis, rendering the SERCA2b-C4orf3 complex exothermic. Loss of C4orf3/ALN improved the energetic efficiency of SERCA2b-dependent Ca2+ transport without affecting SERCA2 expression, thereby reducing adipose tissue thermogenesis and increasing the adiposity of mice. Notably, genetic depletion of C4orf3 resulted in compensatory activation of UCP1-dependent thermogenesis following cold challenge. We demonstrated that genetic loss of both C4orf3 and Ucp1 additively impaired cold tolerance in vivo. Together, this study identifies C4orf3 as the molecular resistor to SERCA2b-mediated Ca2+ import that plays a key role in UCP1-independent thermogenesis and energy balance.","PeriodicalId":9840,"journal":{"name":"Cell metabolism","volume":"31 Suppl 9 1","pages":""},"PeriodicalIF":29.0,"publicationDate":"2025-04-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143789765","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

Pyruvate kinase M2 activation reprograms mitochondria in CD8 T cells, enhancing effector functions and efficacy of anti-PD1 therapy 丙酮酸激酶M2激活可重编程CD8 T细胞中的线粒体，增强抗pd1治疗的效应功能和疗效

IF 29 1区生物学

Cell metabolism Pub Date : 2025-04-07 DOI: 10.1016/j.cmet.2025.03.003

Seyedeh Sahar Mortazavi Farsani, Jignesh Soni, Lu Jin, Anil Kumar Yadav, Shivani Bansal, Tian Mi, Leena Hilakivi-Clarke, Robert Clarke, Benjamin Youngblood, Amrita Cheema, Vivek Verma

{"title":"Pyruvate kinase M2 activation reprograms mitochondria in CD8 T cells, enhancing effector functions and efficacy of anti-PD1 therapy","authors":"Seyedeh Sahar Mortazavi Farsani, Jignesh Soni, Lu Jin, Anil Kumar Yadav, Shivani Bansal, Tian Mi, Leena Hilakivi-Clarke, Robert Clarke, Benjamin Youngblood, Amrita Cheema, Vivek Verma","doi":"10.1016/j.cmet.2025.03.003","DOIUrl":"https://doi.org/10.1016/j.cmet.2025.03.003","url":null,"abstract":"Mitochondria regulate T cell functions and response to immunotherapy. We show that pyruvate kinase M2 (PKM2) activation enhances mitochondria-dependent effector functions in CD8 and chimeric antigen receptor (CAR)-T cells. Multi-omics and 13C-glucose tracer studies showed that PKM2 agonism alters one-carbon metabolism, decreasing methionine levels, resulting in hypomethylated nuclear and mitochondrial DNA and enhancing mitochondrial biogenesis and functions. PKM2 activation increased the recall responses and anti-tumor functions of CD8 T cells, enhancing adoptive cell therapy. In preclinical models, the PKM2 agonist induced CD8 T cell-dependent anti-tumor responses that synergized with anti-programmed death 1 (PD1) therapy. Immunologically, PKM2 agonists boosted the activation of effector T cells while reducing FoxP3+ T regulatory (Treg) cells in the tumors. The anti-PD1 combination enhanced the frequency of tumor-specific activated CD8 T cells. Together, PKM2 agonism increased mitochondrial functions supporting cell cytotoxicity. Hence, pharmacological targeting of PKM2 can be a clinically viable strategy for enhancement of adoptive cell therapy, in situ anti-tumor immune responses, and immune checkpoint blockade therapy.<h3>Video abstract</h3><video controls=\"\" crossorigin=\"anonymous\" data-counter-fields='{\"currObj\":\"MiamiMultiMediaURL\",\"activity\":\"playButton\",\"MMCType\":\"mp4\",\"eid\":\"1-s2.0-S1550413125001068-mmc3.mp4\"}' poster=\"https://ars.els-cdn.com/content/image/1-s2.0-S1550413125001068-mmc3.jpg\" preload=\"auto\" style=\"width:100%\"><source src=\"https://ars.els-cdn.com/content/image/1-s2.0-S1550413125001068-mmc3.mp4\" type=\"video/mp4\"/></video>Download: Download video (57MB)","PeriodicalId":9840,"journal":{"name":"Cell metabolism","volume":"59 1","pages":""},"PeriodicalIF":29.0,"publicationDate":"2025-04-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143789764","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

Reducing Hypothalamic Stem Cell Senescence Protects against Aging-Associated Physiological Decline 减少下丘脑干细胞衰老可防止衰老相关的生理衰退

IF 29 1区生物学

Cell metabolism Pub Date : 2025-04-03 DOI: 10.1016/j.cmet.2025.03.016

Yu-Zhong Xiao, Mi Yang, Ye Xiao, Qi Guo, Yan Huang, Chang-Jun Li, Dongsheng Cai, Xiang-Hang Luo

引用次数: 0

O-GlcNAcylation-mediated endothelial metabolic memory contributes to cardiac damage via small extracellular vesicles O-GlcNAcylation 介导的内皮代谢记忆通过细胞外小泡导致心脏损伤

IF 29 1区生物学

Cell metabolism Pub Date : 2025-04-02 DOI: 10.1016/j.cmet.2025.03.006

Mingge Ding, Rui Shi, Yanyan Du, Pan Chang, Tian Gao, Dema De, Yunan Chen, Man Li, Jun Li, Ke Li, Shuli Cheng, Xiaoming Gu, Juan Li, Shumiao Zhang, Na Feng, Jianzheng Liu, Min Jia, Rong Fan, Jianming Pei, Chao Gao, Feng Fu

{"title":"O-GlcNAcylation-mediated endothelial metabolic memory contributes to cardiac damage via small extracellular vesicles","authors":"Mingge Ding, Rui Shi, Yanyan Du, Pan Chang, Tian Gao, Dema De, Yunan Chen, Man Li, Jun Li, Ke Li, Shuli Cheng, Xiaoming Gu, Juan Li, Shumiao Zhang, Na Feng, Jianzheng Liu, Min Jia, Rong Fan, Jianming Pei, Chao Gao, Feng Fu","doi":"10.1016/j.cmet.2025.03.006","DOIUrl":"https://doi.org/10.1016/j.cmet.2025.03.006","url":null,"abstract":"Diabetic individuals with well-controlled blood glucose still have an increased risk of heart failure. This process may be mediated by metabolic memory, a phenomenon showing that hyperglycemia has long-term negative effects even after normoglycemia. Here, we found that despite later normoglycemia with insulin, long-term diabetes-derived plasma small extracellular vesicle (sEV) miR-15-16 exhibited sustained deleterious effects on cardiomyocytes and induced cardiac dysfunction in healthy animals, displaying a memory feature. Artery endothelial cells were the primary origin of sEV miR-15-16. Mechanistically, the continuous sEV miR-15-16 release is due to the sustained activation of CaMK2a following the high glucose-elicited positive feedback loop of CaMK2a/O-GlcNAcylation in endothelial cells. In patients with diabetes, elevated sEV miR-15-16 was significantly associated with cardiac dysfunction, regardless of blood glucose or HbA1c. Together, our findings demonstrate that diabetes-induced O-GlcNAcylation and activation of CaMK2a mediate endothelial metabolic memory, which induces continuous release of sEV miR-15-16 and subsequent cardiac damage.","PeriodicalId":9840,"journal":{"name":"Cell metabolism","volume":"10 1","pages":""},"PeriodicalIF":29.0,"publicationDate":"2025-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143758395","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 1 of 3 细胞代谢20周年纪念声音：三集之一

IF 29 1区生物学

Cell metabolism Pub Date : 2025-04-01 DOI: 10.1016/j.cmet.2025.03.005

Zoltan Arany, Bao-Liang Song, Roberto Coppari, Jiandie Lin, Nada Kalaany, Gregory Steinberg

引用次数: 0

Feeling the pressure: PIEZO2-positive sensory neurons regulate adipose function 感受压力：piezo2阳性感觉神经元调节脂肪功能

IF 29 1区生物学

Cell metabolism Pub Date : 2025-04-01 DOI: 10.1016/j.cmet.2025.03.007

Henrique Camara, Brian I. Park, Yu-Hua Tseng

引用次数: 0

Can we talk? The cryptic communications of hepatic stellate cells in lipid metabolism 我们能谈谈吗？肝星状细胞在脂质代谢中的隐性通讯

IF 29 1区生物学

Cell metabolism Pub Date : 2025-04-01 DOI: 10.1016/j.cmet.2025.03.008

Scott L. Friedman

引用次数: 0

Embracing the unknown: Proteomic insights into the human microbiome 拥抱未知：人类微生物组的蛋白质组学见解

IF 29 1区生物学

Cell metabolism Pub Date : 2025-04-01 DOI: 10.1016/j.cmet.2025.02.003

Shuqin Zeng, Alexandre Almeida, Dezhi Mu, Shaopu Wang

引用次数: 0

Ceramide-induced FGF13 impairs systemic metabolic health 神经酰胺诱导的FGF13损害全身代谢健康

IF 29 1区生物学

Cell metabolism Pub Date : 2025-03-31 DOI: 10.1016/j.cmet.2025.03.002

Jamal Naderi, Amanda Kelsey Johnson, Himani Thakkar, Bhawna Chandravanshi, Alec Ksiazek, Ajay Anand, Vinnyfred Vincent, Aaron Tran, Anish Kalimireddy, Pratibha Singh, Ayushi Sood, Aasthika Das, Chad Lamar Talbot, Isabella A. Distefano, J. Alan Maschek, James Cox, Ying Li, Scott A. Summers, Donald J. Atkinson, Tursun Turapov, Bhagirath Chaurasia

{"title":"Ceramide-induced FGF13 impairs systemic metabolic health","authors":"Jamal Naderi, Amanda Kelsey Johnson, Himani Thakkar, Bhawna Chandravanshi, Alec Ksiazek, Ajay Anand, Vinnyfred Vincent, Aaron Tran, Anish Kalimireddy, Pratibha Singh, Ayushi Sood, Aasthika Das, Chad Lamar Talbot, Isabella A. Distefano, J. Alan Maschek, James Cox, Ying Li, Scott A. Summers, Donald J. Atkinson, Tursun Turapov, Bhagirath Chaurasia","doi":"10.1016/j.cmet.2025.03.002","DOIUrl":"https://doi.org/10.1016/j.cmet.2025.03.002","url":null,"abstract":"Ceramide accumulation impairs adipocytes’ ability to efficiently store and utilize nutrients, leading to energy and glucose homeostasis deterioration. Using a comparative transcriptomic screen, we identified the non-canonical, non-secreted fibroblast growth factor FGF13 as a ceramide-regulated factor that impairs adipocyte function. Obesity robustly induces FGF13 expression in adipose tissue in mice and humans and is positively associated with glycemic indices of type 2 diabetes. Pharmacological or genetic inhibition of ceramide biosynthesis reduces FGF13 expression. Using mice with loss and gain of function of FGF13, we demonstrate that FGF13 is both necessary and sufficient to impair energy and glucose homeostasis independent of ceramides. Mechanistically, FGF13 exerts these effects by inhibiting mitochondrial content and function, metabolic elasticity, and caveolae formation, which cumulatively impairs glucose utilization and thermogenesis. These studies suggest the therapeutic potential of targeting FGF13 to prevent and treat metabolic diseases.","PeriodicalId":9840,"journal":{"name":"Cell metabolism","volume":"53 1","pages":""},"PeriodicalIF":29.0,"publicationDate":"2025-03-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143736964","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