Cell metabolism最新文献_第8页

Microbial-host isozyme: A novel target in "drug the bug" strategies for diabetes. 微生物宿主同工酶：糖尿病“药虫”策略中的一个新靶点。

Cell metabolism Pub Date : 2023-10-03 DOI: 10.1016/j.cmet.2023.09.008

Guojun Wu, Naisi Zhao, Liping Zhao

引用次数: 0

She didn't start the fire: Mammary duct epithelial cells suppress adipocyte thermogenesis. 她没有引起火灾：乳腺管上皮细胞抑制脂肪细胞的产热。

Cell metabolism Pub Date : 2023-10-03 DOI: 10.1016/j.cmet.2023.09.007

David Merrick

引用次数: 0

Targeting Pathogenic Lafora Bodies in Lafora Disease Using an Antibody-Enzyme Fusion. 使用抗体-酶融合靶向拉福拉病中的致病性拉福拉体。

Cell metabolism Pub Date : 2019-10-01 Epub Date: 2019-07-25 DOI: 10.1016/j.cmet.2019.07.002

M Kathryn Brewer, Annette Uittenbogaard, Grant L Austin, Dyann M Segvich, Anna DePaoli-Roach, Peter J Roach, John J McCarthy, Zoe R Simmons, Jason A Brandon, Zhengqiu Zhou, Jill Zeller, Lyndsay E A Young, Ramon C Sun, James R Pauly, Nadine M Aziz, Bradley L Hodges, Tracy R McKnight, Dustin D Armstrong, Matthew S Gentry

{"title":"Targeting Pathogenic Lafora Bodies in Lafora Disease Using an Antibody-Enzyme Fusion.","authors":"M Kathryn Brewer, Annette Uittenbogaard, Grant L Austin, Dyann M Segvich, Anna DePaoli-Roach, Peter J Roach, John J McCarthy, Zoe R Simmons, Jason A Brandon, Zhengqiu Zhou, Jill Zeller, Lyndsay E A Young, Ramon C Sun, James R Pauly, Nadine M Aziz, Bradley L Hodges, Tracy R McKnight, Dustin D Armstrong, Matthew S Gentry","doi":"10.1016/j.cmet.2019.07.002","DOIUrl":"https://doi.org/10.1016/j.cmet.2019.07.002","url":null,"abstract":"Lafora disease (LD) is a fatal childhood epilepsy caused by recessive mutations in either the EPM2A or EPM2B gene. A hallmark of LD is the intracellular accumulation of insoluble polysaccharide deposits known as Lafora bodies (LBs) in the brain and other tissues. In LD mouse models, genetic reduction of glycogen synthesis eliminates LB formation and rescues the neurological phenotype. Therefore, LBs have become a therapeutic target for ameliorating LD. Herein, we demonstrate that human pancreatic α-amylase degrades LBs. We fused this amylase to a cell-penetrating antibody fragment, and this antibody-enzyme fusion (VAL-0417) degrades LBs in vitro and dramatically reduces LB loads in vivo in Epm2a-/- mice. Using metabolomics and multivariate analysis, we demonstrate that VAL-0417 treatment of Epm2a-/- mice reverses the metabolic phenotype to a wild-type profile. VAL-0417 is a promising drug for the treatment of LD and a putative precision therapy platform for intractable epilepsy.","PeriodicalId":93927,"journal":{"name":"Cell metabolism","volume":"30 4","pages":"689-705.e6"},"PeriodicalIF":0.0,"publicationDate":"2019-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.cmet.2019.07.002","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41223576","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Thermoneutral Housing Accelerates Metabolic Inflammation to Potentiate Atherosclerosis but Not Insulin Resistance. 中温住房会加速代谢炎症，从而加剧动脉粥样硬化，但不会加剧胰岛素抵抗。

Cell metabolism Pub Date : 2016-01-12 Epub Date: 2015-11-05 DOI: 10.1016/j.cmet.2015.10.003

Xiao Yu Tian, Kirthana Ganeshan, Cynthia Hong, Khoa D Nguyen, Yifu Qiu, Jason Kim, Rajendra K Tangirala, Peter Tontonoz, Peter Tonotonoz, Ajay Chawla

{"title":"Thermoneutral Housing Accelerates Metabolic Inflammation to Potentiate Atherosclerosis but Not Insulin Resistance.","authors":"Xiao Yu Tian, Kirthana Ganeshan, Cynthia Hong, Khoa D Nguyen, Yifu Qiu, Jason Kim, Rajendra K Tangirala, Peter Tontonoz, Peter Tonotonoz, Ajay Chawla","doi":"10.1016/j.cmet.2015.10.003","DOIUrl":"10.1016/j.cmet.2015.10.003","url":null,"abstract":"Chronic, low-grade inflammation triggered by excess intake of dietary lipids has been proposed to contribute to the pathogenesis of metabolic disorders, such as obesity, insulin resistance, type 2 diabetes, and atherosclerosis. Although considerable evidence supports a causal association between inflammation and metabolic diseases, most tests of this link have been performed in cold-stressed mice that are housed below their thermoneutral zone. We report here that thermoneutral housing of mice has a profound effect on the development of metabolic inflammation, insulin resistance, and atherosclerosis. Mice housed at thermoneutrality develop metabolic inflammation in adipose tissue and in the vasculature at an accelerated rate. Unexpectedly, this increased inflammatory response contributes to the progression of atherosclerosis but not insulin resistance. These findings not only suggest that metabolic inflammation can be uncoupled from obesity-associated insulin resistance, but also point to how thermal stress might limit our ability to faithfully model human diseases in mice. ","PeriodicalId":93927,"journal":{"name":"Cell metabolism","volume":"23 1","pages":"165-78"},"PeriodicalIF":0.0,"publicationDate":"2016-01-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4715491/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141285662","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Mitochondrial Membrane Potential Identifies Cells with Enhanced Stemness for Cellular Therapy. 线粒体膜电位识别细胞与增强干性细胞治疗。

Cell metabolism Pub Date : 2016-01-12 Epub Date: 2015-12-08 DOI: 10.1016/j.cmet.2015.11.002

Madhusudhanan Sukumar, Jie Liu, Gautam U Mehta, Shashank J Patel, Rahul Roychoudhuri, Joseph G Crompton, Christopher A Klebanoff, Yun Ji, Peng Li, Zhiya Yu, Greg D Whitehill, David Clever, Robert L Eil, Douglas C Palmer, Suman Mitra, Mahadev Rao, Keyvan Keyvanfar, David S Schrump, Ena Wang, Francesco M Marincola, Luca Gattinoni, Warren J Leonard, Pawel Muranski, Toren Finkel, Nicholas P Restifo

{"title":"Mitochondrial Membrane Potential Identifies Cells with Enhanced Stemness for Cellular Therapy.","authors":"Madhusudhanan Sukumar, Jie Liu, Gautam U Mehta, Shashank J Patel, Rahul Roychoudhuri, Joseph G Crompton, Christopher A Klebanoff, Yun Ji, Peng Li, Zhiya Yu, Greg D Whitehill, David Clever, Robert L Eil, Douglas C Palmer, Suman Mitra, Mahadev Rao, Keyvan Keyvanfar, David S Schrump, Ena Wang, Francesco M Marincola, Luca Gattinoni, Warren J Leonard, Pawel Muranski, Toren Finkel, Nicholas P Restifo","doi":"10.1016/j.cmet.2015.11.002","DOIUrl":"https://doi.org/10.1016/j.cmet.2015.11.002","url":null,"abstract":"Long-term survival and antitumor immunity of adoptively transferred CD8(+) T cells is dependent on their metabolic fitness, but approaches to isolate therapeutic T cells based on metabolic features are not well established. Here we utilized a lipophilic cationic dye tetramethylrhodamine methyl ester (TMRM) to identify and isolate metabolically robust T cells based on their mitochondrial membrane potential (ΔΨm). Comprehensive metabolomic and gene expression profiling demonstrated global features of improved metabolic fitness in low-ΔΨm-sorted CD8(+) T cells. Transfer of these low-ΔΨm T cells was associated with superior long-term in vivo persistence and an enhanced capacity to eradicate established tumors compared with high-ΔΨm cells. Use of ΔΨm-based sorting to enrich for cells with superior metabolic features was observed in CD8(+), CD4(+) T cell subsets, and long-term hematopoietic stem cells. This metabolism-based approach to cell selection may be broadly applicable to therapies involving the transfer of HSC or lymphocytes for the treatment of viral-associated illnesses and cancer.","PeriodicalId":93927,"journal":{"name":"Cell metabolism","volume":"23 1","pages":"63-76"},"PeriodicalIF":0.0,"publicationDate":"2016-01-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4747432/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144182307","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Mitochondrial SIRT3 Mediates Adaptive Responses of Neurons to Exercise and Metabolic and Excitatory Challenges. 线粒体SIRT3介导神经元对运动、代谢和兴奋性挑战的适应性反应。

Cell metabolism Pub Date : 2016-01-12 Epub Date: 2015-11-19 DOI: 10.1016/j.cmet.2015.10.013

Aiwu Cheng, Ying Yang, Ye Zhou, Chinmoyee Maharana, Daoyuan Lu, Wei Peng, Yong Liu, Ruiqian Wan, Krisztina Marosi, Magdalena Misiak, Vilhelm A Bohr, Mark P Mattson

{"title":"Mitochondrial SIRT3 Mediates Adaptive Responses of Neurons to Exercise and Metabolic and Excitatory Challenges.","authors":"Aiwu Cheng, Ying Yang, Ye Zhou, Chinmoyee Maharana, Daoyuan Lu, Wei Peng, Yong Liu, Ruiqian Wan, Krisztina Marosi, Magdalena Misiak, Vilhelm A Bohr, Mark P Mattson","doi":"10.1016/j.cmet.2015.10.013","DOIUrl":"https://doi.org/10.1016/j.cmet.2015.10.013","url":null,"abstract":"The impact of mitochondrial protein acetylation status on neuronal function and vulnerability to neurological disorders is unknown. Here we show that the mitochondrial protein deacetylase SIRT3 mediates adaptive responses of neurons to bioenergetic, oxidative, and excitatory stress. Cortical neurons lacking SIRT3 exhibit heightened sensitivity to glutamate-induced calcium overload and excitotoxicity and oxidative and mitochondrial stress; AAV-mediated Sirt3 gene delivery restores neuronal stress resistance. In models relevant to Huntington's disease and epilepsy, Sirt3(-/-) mice exhibit increased vulnerability of striatal and hippocampal neurons, respectively. SIRT3 deficiency results in hyperacetylation of several mitochondrial proteins, including superoxide dismutase 2 and cyclophilin D. Running wheel exercise increases the expression of Sirt3 in hippocampal neurons, which is mediated by excitatory glutamatergic neurotransmission and is essential for mitochondrial protein acetylation homeostasis and the neuroprotective effects of running. Our findings suggest that SIRT3 plays pivotal roles in adaptive responses of neurons to physiological challenges and resistance to degeneration. ","PeriodicalId":93927,"journal":{"name":"Cell metabolism","volume":"23 1","pages":"128-42"},"PeriodicalIF":0.0,"publicationDate":"2016-01-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5141613/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144182308","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Are Astrocytes the Pressure-Reservoirs of Lactate in the Brain? 星形胶质细胞是大脑中乳酸的压力储存库吗？

Cell metabolism Pub Date : 2016-01-12 Epub Date: 2015-11-19 DOI: 10.1016/j.cmet.2015.11.001

Sergey Kasparov

引用次数: 0

Women in Metabolism: Part 3. 新陈代谢中的女性：第三部分。

Cell metabolism Pub Date : 2015-12-01 DOI: 10.1016/j.cmet.2015.11.005

Frances Ashcroft, Erika Pearce, Linda Partridge, Anu Suomalainen, Anne Brunet, Almut Schulze, Yu-Hua Tseng, Jaswinder K Sethi, Karen Reue, Bronwyn Kingwell, Elizabeth McNally, Miriam Cnop, Andrea L Hevener, Sabrina Diano

引用次数: 0

Impairment of central leptin-mediated PI3K signaling manifested as hepatic steatosis independent of hyperphagia and obesity. 中枢瘦素介导的 PI3K 信号转导受损表现为肝脂肪变性，与多食和肥胖无关。

Cell metabolism Pub Date : 2011-12-07 DOI: 10.1016/j.cmet.2011.11.001

James P Warne, Farzad Alemi, Alison S Reed, Jillian M Varonin, Helen Chan, Merisa L Piper, Mark E Mullin, Martin G Myers, Carlos U Corvera, Allison W Xu

{"title":"Impairment of central leptin-mediated PI3K signaling manifested as hepatic steatosis independent of hyperphagia and obesity.","authors":"James P Warne, Farzad Alemi, Alison S Reed, Jillian M Varonin, Helen Chan, Merisa L Piper, Mark E Mullin, Martin G Myers, Carlos U Corvera, Allison W Xu","doi":"10.1016/j.cmet.2011.11.001","DOIUrl":"10.1016/j.cmet.2011.11.001","url":null,"abstract":"Hepatic steatosis is generally thought to develop via peripheral mechanisms associated with obesity. We show that chronic central infusion of leptin suppresses hepatic lipogenic gene expression and reduces triglyceride content via stimulation of hepatic sympathetic activity. This leptin function is independent of feeding and body weight but requires phosphatidylinositol 3-kinase (PI3K) signaling. Attenuation of leptin-induced PI3K signaling, brought about by transgenic expression of phosphatase and tensin homolog (PTEN) in leptin receptor neurons, leads to decreased hepatic sympathetic tone and increased triglyceride levels without affecting adiposity or hepatic insulin signaling. Central leptin's effects on hepatic norepinephrine levels and triglyceride content are blunted in these mutant mice. Simultaneous downregulation of PI3K and signal transducer and activator of transcription-3 (Stat3) in leptin receptor neurons does not exacerbate obesity but causes more severe hepatic steatosis. Together, our results indicate that central cellular leptin resistance in PI3K signaling manifests as hepatic steatosis without causing obesity.","PeriodicalId":93927,"journal":{"name":"Cell metabolism","volume":"14 6","pages":"791-803"},"PeriodicalIF":0.0,"publicationDate":"2011-12-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3240844/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141452357","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

The serine protease matriptase-2 (TMPRSS6) inhibits hepcidin activation by cleaving membrane hemojuvelin. 丝氨酸蛋白酶基质蛋白酶-2 （TMPRSS6）通过切割膜血凝素抑制hepcidin的激活。

Cell metabolism Pub Date : 2008-12-01 Epub Date: 2008-10-30 DOI: 10.1016/j.cmet.2008.09.012

Laura Silvestri, Alessia Pagani, Antonella Nai, Ivana De Domenico, Jerry Kaplan, Clara Camaschella

{"title":"The serine protease matriptase-2 (TMPRSS6) inhibits hepcidin activation by cleaving membrane hemojuvelin.","authors":"Laura Silvestri, Alessia Pagani, Antonella Nai, Ivana De Domenico, Jerry Kaplan, Clara Camaschella","doi":"10.1016/j.cmet.2008.09.012","DOIUrl":"https://doi.org/10.1016/j.cmet.2008.09.012","url":null,"abstract":"The liver peptide hepcidin regulates body iron, is upregulated in iron overload and inflammation, and is downregulated in iron deficiency/hypoxia. The transmembrane serine protease matriptase-2 (TMPRSS6) inhibits the hepcidin response and its mutational inactivation causes iron-deficient anemia in mice and humans. Here we confirm the inhibitory effect of matriptase-2 on hepcidin promoter; we show that matriptase-2 lacking the serine protease domain, identified in the anemic Mask mouse (matriptase-2(MASK)), is fully inactive and that mutant R774C found in patients with genetic iron deficiency has decreased inhibitory activity. Matriptase-2 cleaves hemojuvelin (HJV), a regulator of hepcidin, on plasma membrane; matriptase-2(MASK) shows no cleavage activity and the human mutant only partial cleavage capacity. Matriptase-2 interacts with HJV through the ectodomain since the interaction is conserved in matriptase-2(MASK). The expression of matriptase-2 mutants in zebrafish results in anemia, confirming the matriptase-2 role in iron metabolism and its interaction with HJV.","PeriodicalId":93927,"journal":{"name":"Cell metabolism","volume":"8 6","pages":"502-11"},"PeriodicalIF":0.0,"publicationDate":"2008-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2648389/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144176128","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0