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  • Basal Mitophagy Occurs Independently of PINK1 in Mouse Tissues of High Metabolic Demand
    Cell Metab. (IF 18.164) Pub Date : 2018-01-11
    Thomas G. McWilliams, Alan R. Prescott, Lambert Montava-Garriga, Graeme Ball, François Singh, Erica Barini, Miratul M.K. Muqit, Simon P. Brooks, Ian G. Ganley

    Dysregulated mitophagy has been linked to Parkinson's disease (PD) due to the role of PTEN-induced kinase 1 (PINK1) in mediating depolarization-induced mitophagyin vitro. Elegant mouse reporters have revealed the pervasive nature of basal mitophagyin vivo, yet the role of PINK1 and tissue metabolic context remains unknown. Usingmito-QC, we investigated the contribution of PINK1 to mitophagy in metabolically active tissues. We observed a high degree of mitophagy in neural cells, including PD-relevant mesencephalic dopaminergic neurons and microglia. In all tissues apart from pancreatic islets, loss ofPink1did not influence basal mitophagy, despite disrupting depolarization-induced Parkin activation. Our findings provide the firstin vivoevidence that PINK1 is detectable at basal levels and that basal mammalian mitophagy occurs independently of PINK1. This suggests multiple, yet-to-be-discovered pathways orchestrating mammalian mitochondrial integrity in a context-dependent fashion, and this has profound implications for our molecular understanding of vertebrate mitophagy.

    更新日期:2018-01-11
  • Let-7 Suppresses B Cell Activation through Restricting the Availability of Necessary Nutrients
    Cell Metab. (IF 18.164) Pub Date : 2018-01-11
    Shuai Jiang, Wei Yan, Shizhen Emily Wang, David Baltimore

    The control of uptake and utilization of necessary extracellular nutrients—glucose and glutamine—is an important aspect of B cell activation. Let-7 is a family of microRNAs known to be involved in metabolic control. Here, we employed several engineered mouse models, including B cell-specific overexpression of Lin28a or the let-7a-1/let-7d/let-7f-1 cluster (let-7adf) and knockout of individual let-7 clusters to show that let-7adf specifically inhibits T cell-independent (TI) antigen-induced immunoglobulin (Ig)M antibody production. Both overexpression and deletion of let-7 in this cluster leads to altered TI-IgM production. Mechanistically, let-7adf suppresses the acquisition and utilization of key nutrients, including glucose and glutamine, through directly targeting hexokinase 2 (Hk2) and by repressing a glutamine transporter Slc1a5 and a key degradation enzyme, glutaminase (Gls), a mechanism mediated by regulation of c-Myc. Our results suggest a novel role of let-7adf as a “metabolic brake” on B cell antibody production.

    更新日期:2018-01-11
  • As Extracellular Glutamine Levels Decline, Asparagine Becomes an Essential Amino Acid
    Cell Metab. (IF 18.164) Pub Date : 2018-01-11
    Natalya N. Pavlova, Sheng Hui, Jonathan M. Ghergurovich, Jing Fan, Andrew M. Intlekofer, Richard M. White, Joshua D. Rabinowitz, Craig B. Thompson, Ji Zhang

    When mammalian cells are deprived of glutamine, exogenous asparagine rescues cell survival and growth. Here we report that this rescue results from use of asparagine in protein synthesis. All mammalian cell lines tested lacked cytosolic asparaginase activity and could not utilize asparagine to produce other amino acids or biosynthetic intermediates. Instead, most glutamine-deprived cell lines are capable of sufficient glutamine synthesis to maintain essential amino acid uptake and production of glutamine-dependent biosynthetic precursors, with the exception of asparagine. While experimental introduction of cytosolic asparaginase could enhance the synthesis of glutamine and increase tricarboxylic acid cycle anaplerosis and the synthesis of nucleotide precursors, cytosolic asparaginase suppressed the growth and survival of cells in glutamine-depleted mediumin vitroand severely compromised thein vivogrowth of tumor xenografts. These results suggest that the lack of asparaginase activity represents an evolutionary adaptation to allow mammalian cells to survive pathophysiologic variations in extracellular glutamine.

    更新日期:2018-01-11
  • SERCA2b Cycles Its Way to UCP1-Independent Thermogenesis in Beige Fat
    Cell Metab. (IF 18.164) Pub Date : 2018-01-09
    Emilio P. Mottillo, Vanesa D. Ramseyer, James G. Granneman
    更新日期:2018-01-09
  • Metabolic Reprogramming via Targeting CD38 NADase Augments Adoptive T Cell Therapy
    Cell Metab. (IF 18.164) Pub Date : 2018-01-09
    Mario R. Fernandez, John L. Cleveland
    更新日期:2018-01-09
  • 更新日期:2018-01-09
  • Aminoacylation of Proteins: New Targets for the Old ARSenal
    Cell Metab. (IF 18.164) Pub Date : 2018-01-09
    Seyed Mehdi Jafarnejad, Sung-Hoon Kim, Nahum Sonenberg
    更新日期:2018-01-09
  • Three-Dimensional Adipose Tissue Imaging Reveals Regional Variation in Beige Fat Biogenesis and PRDM16-Dependent Sympathetic Neurite Density
    Cell Metab. (IF 18.164) Pub Date : 2018-01-09
    Jingyi Chi, Zhuhao Wu, Chan Hee J. Choi, Lily Nguyen, Saba Tegegne, Sarah E. Ackerman, Audrey Crane, François Marchildon, Marc Tessier-Lavigne, Paul Cohen
    更新日期:2018-01-09
  • Human CIA2A-FAM96A and CIA2B-FAM96B Integrate Iron Homeostasis and Maturation of Different Subsets of Cytosolic-Nuclear Iron-Sulfur Proteins
    Cell Metab. (IF 18.164) Pub Date : 2018-01-09
    Oliver Stehling, Judita Mascarenhas, Ajay A. Vashisht, Alex D. Sheftel, Brigitte Niggemeyer, Ralf Rösser, Antonio J. Pierik, James A. Wohlschlegel, Roland Lill
    更新日期:2018-01-09
  • Repression of Adipose Tissue Fibrosis through a PRDM16-GTF2IRD1 Complex Improves Systemic Glucose Homeostasis
    Cell Metab. (IF 18.164) Pub Date : 2018-01-09
    Yutaka Hasegawa, Kenji Ikeda, Yong Chen, Diana L. Alba, Daniel Stifler, Kosaku Shinoda, Takashi Hosono, Pema Maretich, Yangyu Yang, Yasushi Ishigaki, Jingyi Chi, Paul Cohen, Suneil K. Koliwad, Shingo Kajimura
    更新日期:2018-01-09
  • An Adipose Tissue Atlas: An Image-Guided Identification of Human-like BAT and Beige Depots in Rodents
    Cell Metab. (IF 18.164) Pub Date : 2018-01-09
    Fang Zhang, Guiyang Hao, Mengle Shao, Kien Nham, Yu An, Qiong Wang, Yi Zhu, Christine M. Kusminski, Gedaa Hassan, Rana K. Gupta, Qiwei Zhai, Xiankai Sun, Philipp E. Scherer, Orhan K. Oz
    更新日期:2018-01-09
  • Anatomical, Physiological, and Functional Diversity of Adipose Tissue
    Cell Metab. (IF 18.164) Pub Date : 2018-01-09
    Rachel K. Zwick, Christian F. Guerrero-Juarez, Valerie Horsley, Maksim V. Plikus
    更新日期:2018-01-09
  • Extracellular Vesicles Provide a Means for Tissue Crosstalk during Exercise
    Cell Metab. (IF 18.164) Pub Date : 2018-01-09
    Martin Whitham, Benjamin L. Parker, Martin Friedrichsen, Janne R. Hingst, Marit Hjorth, William E. Hughes, Casey L. Egan, Lena Cron, Kevin I. Watt, Rhiannon P. Kuchel, Navind Jayasooriah, Emma Estevez, Tim Petzold, Catherine M. Suter, Paul Gregorevic, Bente Kiens, Erik A. Richter, David E. James, Jørgen F.P. Wojtaszewski, Mark A. Febbraio
    更新日期:2018-01-09
  • SnapShot: Niche Determines Adipocyte Character II
    Cell Metab. (IF 18.164) Pub Date : 2018-01-09
    Devika P. Bagchi, Isabel Forss, Susanne Mandrup, Ormond A. MacDougald

    The intrinsic cellular and metabolic properties of an adipocyte are shaped by the specific niche in which it resides. The diverse and discrete locations of major and minor rodent adipose depots are depicted in Part I. In Part II, the molecular and functional characteristics of four major types of adipocytes are described. Identified functions of relatively understudied but undoubtedly important depots are also highlighted.

    更新日期:2018-01-09
  • SnapShot: Niche Determines Adipocyte Character I
    Cell Metab. (IF 18.164) Pub Date : 2018-01-09
    Devika P. Bagchi, Isabel Forss, Susanne Mandrup, Ormond A. MacDougald

    Adipose tissues are complex organs, with central roles in energy homeostasis as well as local functions. Adipocytes develop in diverse, discrete locations throughout the body. Important regional differences in adipocytes exist, and diseases that affect adipose tissues often demonstrate depot-specific effects. Herein, we depict the widespread locations of major and minor rodent adipose depots. Depot-specific molecular and functional characteristics will be described in Part II.

    更新日期:2018-01-09
  • Could Ceramides Become the New Cholesterol?
    Cell Metab. (IF 18.164) Pub Date : 2018-01-04
    Scott A. Summers
    更新日期:2018-01-04
  • Drosophila Perpetuates Nutritional Mutualism by Promoting the Fitness of Its Intestinal Symbiont Lactobacillus plantarum
    Cell Metab. (IF 18.164) Pub Date : 2017-12-28
    Gilles Storelli, Maura Strigini, Théodore Grenier, Loan Bozonnet, Martin Schwarzer, Catherine Daniel, Renata Matos, François Leulier
    更新日期:2017-12-31
  • mTORC1 Inactivation Promotes Colitis-Induced Colorectal Cancer but Protects from APC Loss-Dependent Tumorigenesis
    Cell Metab. (IF 18.164) Pub Date : 2017-12-21
    Marta Brandt, Tatiana P. Grazioso, Mohamad-Ali Fawal, Krishna S. Tummala, Raul Torres-Ruiz, Sandra Rodriguez-Perales, Cristian Perna, Nabil Djouder
    更新日期:2017-12-21
  • mTORC1 Signaling: A Double-Edged Sword in Diabetic β Cells
    Cell Metab. (IF 18.164) Pub Date : 2017-12-21
    Amin Ardestani, Blaz Lupse, Yoshiaki Kido, Gil Leibowitz, Kathrin Maedler
    更新日期:2017-12-21
  • Inactivation of the Glucose-Dependent Insulinotropic Polypeptide Receptor Improves Outcomes following Experimental Myocardial Infarction
    Cell Metab. (IF 18.164) Pub Date : 2017-12-21
    John R. Ussher, Jonathan E. Campbell, Erin E. Mulvihill, Laurie L. Baggio, Holly E. Bates, Brent A. McLean, Keshav Gopal, Megan Capozzi, Bernardo Yusta, Xiemin Cao, Safina Ali, Minsuk Kim, M. Golam Kabir, Yutaka Seino, Jinya Suzuki, Daniel J. Drucker
    更新日期:2017-12-21
  • NAD+ Intermediates: The Biology and Therapeutic Potential of NMN and NR
    Cell Metab. (IF 18.164) Pub Date : 2017-12-14
    Jun Yoshino, Joseph A. Baur, Shin-ichiro Imai
    更新日期:2017-12-15
  • JAK/STAT3-Regulated Fatty Acid β-Oxidation Is Critical for Breast Cancer Stem Cell Self-Renewal and Chemoresistance
    Cell Metab. (IF 18.164) Pub Date : 2017-12-14
    Tianyi Wang, Johannes Francois Fahrmann, Heehyoung Lee, Yi-Jia Li, Satyendra C. Tripathi, Chanyu Yue, Chunyan Zhang, Veronica Lifshitz, Jieun Song, Yuan Yuan, George Somlo, Rahul Jandial, David Ann, Samir Hanash, Richard Jove, Hua Yu
    更新日期:2017-12-15
  • LEAP2 Is an Endogenous Antagonist of the Ghrelin Receptor
    Cell Metab. (IF 18.164) Pub Date : 2017-12-07
    Xuecai Ge, Hong Yang, Maria A. Bednarek, Hadas Galon-Tilleman, Peirong Chen, Michael Chen, Joshua S. Lichtman, Yan Wang, Olivier Dalmas, Yiyuan Yin, Hui Tian, Lutz Jermutus, Joseph Grimsby, Cristina M. Rondinone, Anish Konkar, Daniel D. Kaplan
    更新日期:2017-12-07
  • RevAMPing Mitochondrial Shape to Live Longer
    Cell Metab. (IF 18.164) Pub Date : 2017-12-05
    Lena Pernas, Luca Scorrano
    更新日期:2017-12-05
  • Transcriptional Noise and Somatic Mutations in the Aging Pancreas
    Cell Metab. (IF 18.164) Pub Date : 2017-12-05
    Avital Swisa, Klaus H. Kaestner, Yuval Dor
    更新日期:2017-12-05
  • When Cancer Cells Are Given Lemo[NH3]s, They Make Lemo[NH3]ade
    Cell Metab. (IF 18.164) Pub Date : 2017-12-05
    Mengrou Shan, Costas A. Lyssiotis
    更新日期:2017-12-05
  • MAIT Cells: A Link between Gut Integrity and Type 1 Diabetes
    Cell Metab. (IF 18.164) Pub Date : 2017-12-05
    Elke Gülden, Noah Palm, Kevan C. Herold
    更新日期:2017-12-05
  • Waste Not, Want Not: Lactate Oxidation Fuels the TCA Cycle
    Cell Metab. (IF 18.164) Pub Date : 2017-12-05
    Inmaculada Martínez-Reyes, Navdeep S. Chandel
    更新日期:2017-12-05
  • Sensing and Transmitting Intracellular Amino Acid Signals through Reversible Lysine Aminoacylations
    Cell Metab. (IF 18.164) Pub Date : 2017-11-30
    Xia-Di He, Wei Gong, Jia-Nong Zhang, Ji Nie, Cui-Fang Yao, Fu-Shen Guo, Yan Lin, Xiao-Hui Wu, Feng Li, Jie Li, Wei-Cheng Sun, En-Duo Wang, Yan-Peng An, Hui-Ru Tang, Guo-Quan Yan, Peng-Yuan Yang, Yun Wei, Yun-Zi Mao, Peng-Cheng Lin, Jian-Yuan Zhao, Yanhui Xu, Wei Xu, Shi-Min Zhao
    更新日期:2017-12-01
  • GDF15—From Biomarker to Allostatic Hormone
    Cell Metab. (IF 18.164) Pub Date : 2017-11-28
    Stephen O’Rahilly
    更新日期:2017-11-29
  • AMPK: Sensing Glucose as well as Cellular Energy Status
    Cell Metab. (IF 18.164) Pub Date : 2017-11-16
    Sheng-Cai Lin, D. Grahame Hardie

    Mammalian AMPK is known to be activated by falling cellular energy status, signaled by rising AMP/ATP and ADP/ATP ratios. We review recent information about how this occurs but also discuss new studies suggesting that AMPK is able to sense glucose availability independently of changes in adenine nucleotides. The glycolytic intermediate fructose-1,6-bisphosphate (FBP) is sensed by aldolase, which binds to the v-ATPase on the lysosomal surface. In the absence of FBP, interactions between aldolase and the v-ATPase are altered, allowing formation of an AXIN-based AMPK-activation complex containing the v-ATPase, Ragulator, AXIN, LKB1, and AMPK, causing increased Thr172 phosphorylation and AMPK activation. This nutrient-sensing mechanism activates AMPK but also primes it for further activation if cellular energy status subsequently falls. Glucose sensing at the lysosome, in which AMPK and other components of the activation complex act antagonistically with another key nutrient sensor, mTORC1, may have been one of the ancestral roles of AMPK.

    更新日期:2017-11-19
  • Brown Fat AKT2 Is a Cold-Induced Kinase that Stimulates ChREBP-Mediated De Novo Lipogenesis to Optimize Fuel Storage and Thermogenesis
    Cell Metab. (IF 18.164) Pub Date : 2017-11-16
    Joan Sanchez-Gurmaches, Yuefeng Tang, Naja Zenius Jespersen, Martina Wallace, Camila Martinez Calejman, Sharvari Gujja, Huawei Li, Yvonne J.K. Edwards, Christian Wolfrum, Christian M. Metallo, Søren Nielsen, Camilla Scheele, David A. Guertin

    Brown adipose tissue (BAT) is a therapeutic target for metabolic diseases; thus, understanding its metabolic circuitry is clinically important. Many studies of BAT compare rodents mildly cold to those severely cold. Here, we compared BAT remodeling between thermoneutral and mild-cold-adapted mice, conditions more relevant to humans. Although BAT is renowned for catabolic β-oxidative capacity, we find paradoxically that the anabolicde novolipogenesis (DNL) genes encoding ACLY, ACSS2, ACC, and FASN were among the most upregulated by mild cold and that, in humans, DNL correlates withUcp1expression. The regulation and function of adipocyte DNL and its association with thermogenesis are not understood. We provide evidence suggesting that AKT2 drives DNL in adipocytes by stimulating ChREBPβ transcriptional activity and that cold induces the AKT2-ChREBP pathway in BAT to optimize fuel storage and thermogenesis. These data provide insight into adipocyte DNL regulation and function and illustrate the metabolic flexibility of thermogenesis.

    更新日期:2017-11-19
  • AMPK: Sensing Glucose as well as Cellular Energy Status
    Cell Metab. (IF 18.164) Pub Date : 2017-11-16
    Sheng-Cai Lin, D. Grahame Hardie
    更新日期:2017-11-19
  • Brown Fat AKT2 Is a Cold-Induced Kinase that Stimulates ChREBP-Mediated De Novo Lipogenesis to Optimize Fuel Storage and Thermogenesis
    Cell Metab. (IF 18.164) Pub Date : 2017-11-16
    Joan Sanchez-Gurmaches, Yuefeng Tang, Naja Zenius Jespersen, Martina Wallace, Camila Martinez Calejman, Sharvari Gujja, Huawei Li, Yvonne J.K. Edwards, Christian Wolfrum, Christian M. Metallo, Søren Nielsen, Camilla Scheele, David A. Guertin
    更新日期:2017-11-19
  • CD38-NAD+Axis Regulates Immunotherapeutic Anti-Tumor T Cell Response
    Cell Metab. (IF 18.164) Pub Date : 2017-11-09
    Shilpak Chatterjee, Anusara Daenthanasanmak, Paramita Chakraborty, Megan W. Wyatt, Payal Dhar, Shanmugam Paneer Selvam, Jianing Fu, Jinyu Zhang, Hung Nguyen, Inhong Kang, Kyle Toth, Mazen Al-Homrani, Mahvash Husain, Gyda Beeson, Lauren Ball, Kristi Helke, Shahid Husain, Elizabeth Garrett-Mayer, Gary Hardiman, Meenal Mehrotra, Michael I. Nishimura, Craig C. Beeson, Melanie Gubbels Bupp, Jennifer Wu, Besim Ogretmen, Chrystal M. Paulos, Jeffery Rathmell, Xue-Zhong Yu, Shikhar Mehrotra

    Heightened effector function and prolonged persistence, the key attributes of Th1 and Th17 cells, respectively, are key features of potent anti-tumor T cells. Here, we establishedex vivoculture conditions to generate hybrid Th1/17 cells, which persisted long-termin vivowhile maintaining their effector function. Using transcriptomics and metabolic profiling approaches, we showed that the enhanced anti-tumor property of Th1/17 cells was dependent on the increased NAD+-dependent activity of the histone deacetylase Sirt1. Pharmacological or genetic inhibition of Sirt1 activity impaired the anti-tumor potential of Th1/17 cells. Importantly, T cells with reduced surface expression of the NADase CD38 exhibited intrinsically higher NAD+, enhanced oxidative phosphorylation, higher glutaminolysis, and altered mitochondrial dynamics that vastly improved tumor control. Lastly, blocking CD38 expression improved tumor control even when using Th0 anti-tumor T cells. Thus, strategies targeting the CD38-NAD+axis could increase the efficacy of anti-tumor adoptive T cell therapy.

    更新日期:2017-11-10
  • Advances in Hypoxia-Inducible Factor Biology
    Cell Metab. (IF 18.164) Pub Date : 2017-11-09
    Hani Choudhry, Adrian L. Harris

    Hypoxia-inducible factor (HIF), a central regulator for detecting and adapting to cellular oxygen levels, transcriptionally activates genes modulating oxygen homeostasis and metabolic activation. Beyond this, HIF influences many other processes. Hypoxia, in part through HIF-dependent mechanisms, influences epigenetic factors, including DNA methylation and histone acetylation, which modulate hypoxia-responsive gene expression in cells. Hypoxia profoundly affects expression of many noncoding RNAs classes that have clinicopathological implications in cancer. HIF can regulate noncoding RNAs production, while, conversely, noncoding RNAs can modulate HIF expression. There is recent evidence for crosstalk between circadian rhythms and hypoxia-induced signaling, suggesting involvement of molecular clocks in adaptation to fluxes in nutrient and oxygen sensing. HIF induces increased production of cellular vesicles facilitating intercellular communication at a distance—for example, promoting angiogenesis in hypoxic tumors. Understanding the complex networks underlying cellular and genomic regulation in response to hypoxia via HIF may identify novel and specific therapeutic targets.

    更新日期:2017-11-10
  • Mechanisms by which a Very-Low-Calorie Diet Reverses Hyperglycemia in a Rat Model of Type 2 Diabetes
    Cell Metab. (IF 18.164) Pub Date : 2017-11-09
    Rachel J. Perry, Liang Peng, Gary W. Cline, Yongliang Wang, Aviva Rabin-Court, Joongyu D. Song, Dongyan Zhang, Xian-Man Zhang, Yuichi Nozaki, Sylvie Dufour, Kitt Falk Petersen, Gerald I. Shulman

    Caloric restriction rapidly reverses type 2 diabetes (T2D), but the mechanism(s) of this reversal are poorly understood. Here we show that 3 days of a very-low-calorie diet (VLCD, one-quarter their typical intake) lowered plasma glucose and insulin concentrations in a rat model of T2D without altering body weight. The lower plasma glucose was associated with a 30% reduction in hepatic glucose production resulting from suppression of both gluconeogenesis from pyruvate carboxylase (VPC), explained by a reduction in hepatic acetyl-CoA content, and net hepatic glycogenolysis. In addition, VLCD resulted in reductions in hepatic triglyceride and diacylglycerol content and PKCɛ translocation, associated with improved hepatic insulin sensitivity. Taken together, these data show that there are pleotropic mechanisms by which VLCD reverses hyperglycemia in a rat model of T2D, including reduced DAG-PKCɛ-induced hepatic insulin resistance, reduced hepatic glycogenolysis, and reduced hepatic acetyl-CoA content, PC flux, and gluconeogenesis.

    更新日期:2017-11-10
  • CD38-NAD+Axis Regulates Immunotherapeutic Anti-Tumor T Cell Response
    Cell Metab. (IF 18.164) Pub Date : 2017-11-09
    Shilpak Chatterjee, Anusara Daenthanasanmak, Paramita Chakraborty, Megan W. Wyatt, Payal Dhar, Shanmugam Paneer Selvam, Jianing Fu, Jinyu Zhang, Hung Nguyen, Inhong Kang, Kyle Toth, Mazen Al-Homrani, Mahvash Husain, Gyda Beeson, Lauren Ball, Kristi Helke, Shahid Husain, Elizabeth Garrett-Mayer, Gary Hardiman, Meenal Mehrotra, Michael I. Nishimura, Craig C. Beeson, Melanie Gubbels Bupp, Jennifer Wu, Besim Ogretmen, Chrystal M. Paulos, Jeffery Rathmell, Xue-Zhong Yu, Shikhar Mehrotra
    更新日期:2017-11-10
  • Advances in Hypoxia-Inducible Factor Biology
    Cell Metab. (IF 18.164) Pub Date : 2017-11-09
    Hani Choudhry, Adrian L. Harris
    更新日期:2017-11-10
  • Mechanisms by which a Very-Low-Calorie Diet Reverses Hyperglycemia in a Rat Model of Type 2 Diabetes
    Cell Metab. (IF 18.164) Pub Date : 2017-11-09
    Rachel J. Perry, Liang Peng, Gary W. Cline, Yongliang Wang, Aviva Rabin-Court, Joongyu D. Song, Dongyan Zhang, Xian-Man Zhang, Yuichi Nozaki, Sylvie Dufour, Kitt Falk Petersen, Gerald I. Shulman
    更新日期:2017-11-10
  • NFIL-trating the Host Circadian Rhythm—Microbes Fine-Tune the Epithelial Clock
    Cell Metab. (IF 18.164) Pub Date : 2017-11-07
    Christoph A. Thaiss, Samuel P. Nobs, Eran Elinav
    更新日期:2017-11-07
  • 更新日期:2017-11-07
  • What Ignites UCP1?
    Cell Metab. (IF 18.164) Pub Date : 2017-11-07
    Barbara Cannon, Jan Nedergaard
    更新日期:2017-11-07
  • Glial Cell Evolution: The Origins of a Lipid Store
    Cell Metab. (IF 18.164) Pub Date : 2017-11-07
    Klaus-Armin Nave, Iva D. Tzvetanova, Stefanie Schirmeier
    更新日期:2017-11-07
  • Dealing with Consequences of Irreproducibility and Modifying the Published Literature: Retractions versus Revisions
    Cell Metab. (IF 18.164) Pub Date : 2017-11-07
    David J. Glass, Jeffrey S. Flier

    One of the barriers to revising the literature when new data are produced, demonstrating the lack of reproducibility of particular published findings, is the stigma associated with the current tools available, most notably the use of retractions. We suggest an additional tool: revisions, which could be linked to prior manuscripts by the original authors and by others (upon peer review). We hope new approaches such as the ability to revise prior reports will help to keep the literature up-to-date and representative of the most complete understanding of an issue.

    更新日期:2017-11-07
  • Intermittent Fasting Promotes White Adipose Browning and Decreases Obesity by Shaping the Gut Microbiota
    Cell Metab. (IF 18.164) Pub Date : 2017-11-07
    Guolin Li, Cen Xie, Siyu Lu, Robert G. Nichols, Yuan Tian, Licen Li, Daxeshkumar Patel, Yinyan Ma, Chad N. Brocker, Tingting Yan, Kristopher W. Krausz, Rong Xiang, Oksana Gavrilova, Andrew D. Patterson, Frank J. Gonzalez

    (Cell Metabolism 26, 672–685; October 3, 2017)

    更新日期:2017-11-07
  • 17β-Estradiol Directly Lowers Mitochondrial Membrane Microviscosity and Improves Bioenergetic Function in Skeletal Muscle
    Cell Metab. (IF 18.164) Pub Date : 2017-11-02
    Maria J. Torres, Kim A. Kew, Terence E. Ryan, Edward Ross Pennington, Chien-Te Lin, Katherine A. Buddo, Amy M. Fix, Cheryl A. Smith, Laura A. Gilliam, Sira Karvinen, Dawn A. Lowe, Espen E. Spangenburg, Tonya N. Zeczycki, Saame Raza Shaikh, P. Darrell Neufer

    Menopause results in a progressive decline in 17β-estradiol (E2) levels, increased adiposity, decreased insulin sensitivity, and a higher risk for type 2 diabetes. Estrogen therapies can help reverse these effects, but the mechanism(s) by which E2 modulates susceptibility to metabolic disease is not well understood. In young C57BL/6N mice, short-term ovariectomy decreased—whereas E2 therapy restored—mitochondrial respiratory function, cellular redox state (GSH/GSSG), and insulin sensitivity in skeletal muscle. E2 was detected by liquid chromatography-mass spectrometry in mitochondrial membranes and varied according to whole-body E2 status independently of ERα. Loss of E2 increased mitochondrial membrane microviscosity and H2O2emitting potential, whereas E2 administrationin vivoandin vitrorestored membrane E2 content, microviscosity, complex I and I + III activities, H2O2emitting potential, and submaximal OXPHOS responsiveness. These findings demonstrate that E2 directly modulates membrane biophysical properties and bioenergetic function in mitochondria, offering a direct mechanism by which E2 status broadly influences energy homeostasis.

    更新日期:2017-11-02
  • Artemether Does Not Turn α Cells into β Cells
    Cell Metab. (IF 18.164) Pub Date : 2017-11-02
    Talitha van der Meulen, Sharon Lee, Els Noordeloos, Cynthia J. Donaldson, Michael W. Adams, Glyn M. Noguchi, Alex M. Mawla, Mark O. Huising

    Pancreatic α cells retain considerable plasticity and can, under the right circumstances, transdifferentiate into functionally mature β cells. In search of a targetable mechanistic basis, a recent paper suggested that the widely used anti-malaria drug artemether suppresses the α cell transcription factor Arx to promote transdifferentiation into β cells. However, key initial experiments in this paper were carried out in islet cell lines, and most subsequent validation experiments implied transdifferentiation without direct demonstration of α to β cell conversion. Indeed, we find no evidence that artemether promotes transdifferentiation of primary α cells into β cells. Moreover, artemether reducesIns2expression in primary β cells >100-fold, suppresses glucose uptake, and abrogates β cell calcium responses and insulin secretion in response to glucose. Our observations suggest that artemether induces general islet endocrine cell dedifferentiation and call into question the utility of artemisinins to promote α to β cell transdifferentiation in treating diabetes.

    更新日期:2017-11-02
  • 17β-Estradiol Directly Lowers Mitochondrial Membrane Microviscosity and Improves Bioenergetic Function in Skeletal Muscle
    Cell Metab. (IF 18.164) Pub Date : 2017-11-02
    Maria J. Torres, Kim A. Kew, Terence E. Ryan, Edward Ross Pennington, Chien-Te Lin, Katherine A. Buddo, Amy M. Fix, Cheryl A. Smith, Laura A. Gilliam, Sira Karvinen, Dawn A. Lowe, Espen E. Spangenburg, Tonya N. Zeczycki, Saame Raza Shaikh, P. Darrell Neufer
    更新日期:2017-11-02
  • Artemether Does Not Turn α Cells into β Cells
    Cell Metab. (IF 18.164) Pub Date : 2017-11-02
    Talitha van der Meulen, Sharon Lee, Els Noordeloos, Cynthia J. Donaldson, Michael W. Adams, Glyn M. Noguchi, Alex M. Mawla, Mark O. Huising
    更新日期:2017-11-02
  • Dietary Restriction and AMPK Increase Lifespan via Mitochondrial Network and Peroxisome Remodeling
    Cell Metab. (IF 18.164) Pub Date : 2017-10-26
    Heather J. Weir, Pallas Yao, Frank K. Huynh, Caroline C. Escoubas, Renata L. Goncalves, Kristopher Burkewitz, Raymond Laboy, Matthew D. Hirschey, William B. Mair

    Mitochondrial network remodeling between fused and fragmented states facilitates mitophagy, interaction with other organelles, and metabolic flexibility. Aging is associated with a loss of mitochondrial network homeostasis, but cellular processes causally linking these changes to organismal senescence remain unclear. Here, we show that AMP-activated protein kinase (AMPK) and dietary restriction (DR) promote longevity inC. elegansvia maintaining mitochondrial network homeostasis and functional coordination with peroxisomes to increase fatty acid oxidation (FAO). Inhibiting fusion or fission specifically blocks AMPK- and DR-mediated longevity. Strikingly, however, preserving mitochondrial network homeostasis during aging by co-inhibition of fusion and fission is sufficient itself to increase lifespan, while dynamic network remodeling is required for intermittent fasting-mediated longevity. Finally, we show that increasing lifespan via maintaining mitochondrial network homeostasis requires FAO and peroxisomal function. Together, these data demonstrate that mechanisms that promote mitochondrial homeostasis and plasticity can be targeted to promote healthy aging.

    更新日期:2017-10-27
  • Abrogating Mitochondrial Dynamics in Mouse Hearts Accelerates Mitochondrial Senescence
    Cell Metab. (IF 18.164) Pub Date : 2017-10-26
    Moshi Song, Antonietta Franco, Julie A. Fleischer, Lihong Zhang, Gerald W. Dorn

    Mitochondrial fusion and fission are critical to heart health; genetically interrupting either is rapidly lethal. To understand whether it is loss of, or the imbalance between, fusion and fission that underlies observed cardiac phenotypes, we engineered mice in which Mfn-mediated fusion and Drp1-mediated fission could be concomitantly abolished. Compared to fusion-defective Mfn1/Mfn2 cardiac knockout or fission-defective Drp1 cardiac knockout mice, Mfn1/Mfn2/Drp1 cardiac triple-knockout mice survived longer and manifested a unique pathological form of cardiac hypertrophy. Over time, however, combined abrogation of fission and fusion provoked massive progressive mitochondrial accumulation that severely distorted cardiomyocyte sarcomeric architecture. Mitochondrial biogenesis was not responsible for mitochondrial superabundance, whereas mitophagy was suppressed despite impaired mitochondrial proteostasis. Similar but milder defects were observed in aged hearts. Thus, cardiomyopathies linked to dynamic imbalance between fission and fusion are temporarily mitigated by forced mitochondrial adynamism at the cost of compromising mitochondrial quantity control and accelerating mitochondrial senescence.

    更新日期:2017-10-27
  • Overlapping Brain Circuits for Homeostatic and Hedonic Feeding
    Cell Metab. (IF 18.164) Pub Date : 2017-10-26
    Mark A. Rossi, Garret D. Stuber

    Central regulation of food intake is a key mechanism contributing to energy homeostasis. Many neural circuits that are thought to orchestrate feeding behavior overlap with the brain’s reward circuitry both anatomically and functionally. Manipulation of numerous neural pathways can simultaneously influence food intake and reward. Two key systems underlying these processes—those controlling homeostatic and hedonic feeding—are often treated as independent. Homeostatic feeding is necessary for basic metabolic processes and survival, while hedonic feeding is driven by sensory perception or pleasure. Despite this distinction, their functional and anatomical overlap implies considerable interaction that is often overlooked. Here, we argue that the neurocircuits controlling homeostatic feeding and hedonic feeding are not completely dissociable given the current data and urge researchers to assess behaviors extending beyond food intake in investigations of the neural control of feeding.

    更新日期:2017-10-27
  • System-wide Benefits of Intermeal Fasting by Autophagy
    Cell Metab. (IF 18.164) Pub Date : 2017-10-26
    Nuria Martinez-Lopez, Elena Tarabra, Miriam Toledo, Marina Garcia-Macia, Srabani Sahu, Luisa Coletto, Ana Batista-Gonzalez, Nir Barzilai, Jeffrey E. Pessin, Gary J. Schwartz, Sander Kersten, Rajat Singh

    Autophagy failure is associated with metabolic insufficiency. Although caloric restriction (CR) extends healthspan, its adherence in humans is poor. We established an isocaloric twice-a-day (ITAD) feeding model wherein ITAD-fed mice consume the same food amount asad libitumcontrols but at two short windows early and late in the diurnal cycle. We hypothesized that ITAD feeding will provide two intervals of intermeal fasting per circadian period and induce autophagy. We show that ITAD feeding modifies circadian autophagy and glucose/lipid metabolism that correlate with feeding-driven changes in circulating insulin. ITAD feeding decreases adiposity and, unlike CR, enhances muscle mass. ITAD feeding drives energy expenditure, lowers lipid levels, suppresses gluconeogenesis, and prevents age/obesity-associated metabolic defects. Using liver-, adipose-, myogenic-, and proopiomelanocortin neuron-specific autophagy-null mice, we mapped the contribution of tissue-specific autophagy to system-wide benefits of ITAD feeding. Our studies suggest that consuming two meals a day without CR could prevent the metabolic syndrome.

    更新日期:2017-10-27
  • Dietary Restriction and AMPK Increase Lifespan via Mitochondrial Network and Peroxisome Remodeling
    Cell Metab. (IF 18.164) Pub Date : 2017-10-26
    Heather J. Weir, Pallas Yao, Frank K. Huynh, Caroline C. Escoubas, Renata L. Goncalves, Kristopher Burkewitz, Raymond Laboy, Matthew D. Hirschey, William B. Mair
    更新日期:2017-10-27
  • Abrogating Mitochondrial Dynamics in Mouse Hearts Accelerates Mitochondrial Senescence
    Cell Metab. (IF 18.164) Pub Date : 2017-10-26
    Moshi Song, Antonietta Franco, Julie A. Fleischer, Lihong Zhang, Gerald W. Dorn
    更新日期:2017-10-27
  • Overlapping Brain Circuits for Homeostatic and Hedonic Feeding
    Cell Metab. (IF 18.164) Pub Date : 2017-10-26
    Mark A. Rossi, Garret D. Stuber
    更新日期:2017-10-27
  • System-wide Benefits of Intermeal Fasting by Autophagy
    Cell Metab. (IF 18.164) Pub Date : 2017-10-26
    Nuria Martinez-Lopez, Elena Tarabra, Miriam Toledo, Marina Garcia-Macia, Srabani Sahu, Luisa Coletto, Ana Batista-Gonzalez, Nir Barzilai, Jeffrey E. Pessin, Gary J. Schwartz, Sander Kersten, Rajat Singh
    更新日期:2017-10-27
  • In Vivo Imaging of Glutamine Metabolism to the Oncometabolite 2-Hydroxyglutarate in IDH1/2 Mutant Tumors
    Cell Metab. (IF 18.164) Pub Date : 2017-10-19
    Lucia Salamanca-Cardona, Hardik Shah, Alex J. Poot, Fabian M. Correa, Valentina Di Gialleonardo, Hui Lui, Vesselin Z. Miloushev, Kristin L. Granlund, Sui S. Tee, Justin R. Cross, Craig B. Thompson, Kayvan R. Keshari

    The oncometabolite 2-hydroxyglutarate (2-HG) is a signature biomarker in various cancers, where it accumulates as a result of mutations in isocitrate dehydrogenase (IDH). The metabolic source of 2-HG, in a wide variety of cancers, dictates both its generation and also potential therapeutic strategies, but this remains difficult to accessin vivo. Here, utilizing patient-derived chondrosarcoma cells harboring endogenous mutations in IDH1 and IDH2, we report that 2-HG can be rapidly generated from glutaminein vitro. Then, using hyperpolarized magnetic resonance imaging (HP-MRI), we demonstrate thatin vivoHP [1-13C] glutamine can be used to non-invasively measure glutamine-derived HP 2-HG production. This can be readily modulated utilizing a selective IDH1 inhibitor, opening the door to targeting glutamine-derived 2-HG therapeutically. Rapid rates of HP 2-HG generationin vivofurther demonstrate that, in a context-dependent manner, glutamine can be a primary carbon source for 2-HG production in mutant IDH tumors.

    更新日期:2017-10-19
  • CANTOS Ushers in a New Calculus of Inflammasome Targeting for Vascular Protection—and Maybe More
    Cell Metab. (IF 18.164) Pub Date : 2017-10-19
    Subodh Verma, Lawrence A. Leiter, Deepak L. Bhatt

    Despite overwhelming basic science linking inflammation to the pathobiology of atherothrombosis, the specific clinical evidence indicating cardiovascular benefits from anti-inflammatory pharmacotherapy has been lacking. The CANTOS trial ( Ridker et al., 2017a ) now provides the first largescale proof of concept that inflammasome targeting can reduce cardiovascular events—and, surprisingly, lung cancer.

    更新日期:2017-10-19
Some contents have been Reproduced with permission of the American Chemical Society.
Some contents have been Reproduced by permission of The Royal Society of Chemistry.
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