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  • Molecular Integration of Incretin and Glucocorticoid Action Reverses Immunometabolic Dysfunction and Obesity
    Cell Metab. (IF 18.164) Pub Date : 2017-09-21
    Carmelo Quarta, Christoffer Clemmensen, Zhimeng Zhu, Bin Yang, Sini S. Joseph, Dominik Lutter, Chun-Xia Yi, Elisabeth Graf, Cristina García-Cáceres, Beata Legutko, Katrin Fischer, Robert Brommage, Philippe Zizzari, Bernardo S. Franklin, Martin Krueger, Marco Koch, Sabine Vettorazzi, Pengyun Li, Susanna M. Hofmann, Mostafa Bakhti, Aimée Bastidas-Ponce, Heiko Lickert, Tim M. Strom, Valerie Gailus-Durner, Ingo Bechmann, Diego Perez-Tilve, Jan Tuckermann, Martin Hrabě de Angelis, Darleen Sandoval, Daniela Cota, Eicke Latz, Randy J. Seeley, Timo D. Müller, Richard D. DiMarchi, Brian Finan, Matthias H. Tschöp

    Chronic inflammation has been proposed to contribute to the pathogenesis of diet-induced obesity. However, scarce therapeutic options are available to treat obesity and the associated immunometabolic complications. Glucocorticoids are routinely employed for the management of inflammatory diseases, but their pleiotropic nature leads to detrimental metabolic side effects. We developed a glucagon-like peptide-1 (GLP-1)-dexamethasone co-agonist in which GLP-1 selectively delivers dexamethasone to GLP-1 receptor-expressing cells. GLP-1-dexamethasone lowers body weight up to 25% in obese mice by targeting the hypothalamic control of feeding and by increasing energy expenditure. This strategy reverses hypothalamic and systemic inflammation while improving glucose tolerance and insulin sensitivity. The selective preference for GLP-1 receptor bypasses deleterious effects of dexamethasone on glucose handling, bone integrity, and hypothalamus-pituitary-adrenal axis activity. Thus, GLP-1-directed glucocorticoid pharmacology represents a safe and efficacious therapy option for diet-induced immunometabolic derangements and the resulting obesity.

    更新日期:2017-09-21
  • Molecular Integration of Incretin and Glucocorticoid Action Reverses Immunometabolic Dysfunction and Obesity
    Cell Metab. (IF 18.164) Pub Date : 2017-09-21
    Carmelo Quarta, Christoffer Clemmensen, Zhimeng Zhu, Bin Yang, Sini S. Joseph, Dominik Lutter, Chun-Xia Yi, Elisabeth Graf, Cristina García-Cáceres, Beata Legutko, Katrin Fischer, Robert Brommage, Philippe Zizzari, Bernardo S. Franklin, Martin Krueger, Marco Koch, Sabine Vettorazzi, Pengyun Li, Susanna M. Hofmann, Mostafa Bakhti, Aimée Bastidas-Ponce, Heiko Lickert, Tim M. Strom, Valerie Gailus-Durner, Ingo Bechmann, Diego Perez-Tilve, Jan Tuckermann, Martin Hrabě de Angelis, Darleen Sandoval, Daniela Cota, Eicke Latz, Randy J. Seeley, Timo D. Müller, Richard D. DiMarchi, Brian Finan, Matthias H. Tschöp
    更新日期:2017-09-21
  • Intermittent Fasting Promotes White Adipose Browning and Decreases Obesity by Shaping the Gut Microbiota
    Cell Metab. (IF 18.164) Pub Date : 2017-09-14
    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

    While activation of beige thermogenesis is a promising approach for treatment of obesity-associated diseases, there are currently no known pharmacological means of inducing beiging in humans. Intermittent fasting is an effective and natural strategy for weight control, but the mechanism for its efficacy is poorly understood. Here, we show that an every-other-day fasting (EODF) regimen selectively stimulates beige fat development within white adipose tissue and dramatically ameliorates obesity, insulin resistance, and hepatic steatosis. EODF treatment results in a shift in the gut microbiota composition leading to elevation of the fermentation products acetate and lactate and to the selective upregulation of monocarboxylate transporter 1 expression in beige cells. Microbiota-depleted mice are resistance to EODF-induced beiging, while transplantation of the microbiota from EODF-treated mice to microbiota-depleted mice activates beiging and improves metabolic homeostasis. These findings provide a new gut-microbiota-driven mechanism for activating adipose tissue browning and treating metabolic diseases.

    更新日期:2017-09-15
  • A Predictive Model for Selective Targeting of the Warburg Effect through GAPDH Inhibition with a Natural Product
    Cell Metab. (IF 18.164) Pub Date : 2017-09-14
    Maria V. Liberti, Ziwei Dai, Suzanne E. Wardell, Joshua A. Baccile, Xiaojing Liu, Xia Gao, Robert Baldi, Mahya Mehrmohamadi, Marc O. Johnson, Neel S. Madhukar, Alexander A. Shestov, Iok I. Christine Chio, Olivier Elemento, Jeffrey C. Rathmell, Frank C. Schroeder, Donald P. McDonnell, Jason W. Locasale

    Targeted cancer therapies that use genetics are successful, but principles for selectively targeting tumor metabolism that is also dependent on the environment remain unknown. We now show that differences in rate-controlling enzymes during the Warburg effect (WE), the most prominent hallmark of cancer cell metabolism, can be used to predict a response to targeting glucose metabolism. We establish a natural product, koningic acid (KA), to be a selective inhibitor of GAPDH, an enzyme we characterize to have differential control properties over metabolism during the WE. With machine learning and integrated pharmacogenomics and metabolomics, we demonstrate that KA efficacy is not determined by the status of individual genes, but by the quantitative extent of the WE, leading to a therapeutic window in vivo. Thus, the basis of targeting the WE can be encoded by molecular principles that extend beyond the status of individual genes.

    更新日期:2017-09-15
  • Dense Intra-adipose Sympathetic Arborizations Are Essential for Cold-Induced Beiging of Mouse White Adipose Tissue
    Cell Metab. (IF 18.164) Pub Date : 2017-09-14
    Haochen Jiang, Xiaofan Ding, Ying Cao, Huanhuan Wang, Wenwen Zeng

    Efferent signals from the central nervous system represent a key layer of regulation of white adipose tissue (WAT). However, the mechanism by which efferent neural signals control WAT metabolism remains to be better understood. Here, we exploit the volume fluorescence-imaging technique to visualize the neural arborizations in mouse inguinal WAT at single-fiber resolution. The imaging reveals a dense network of sympathetic arborizations that had been previously undetected by conventional methods, with sympathetic fibers being in close apposition to > 90% of adipocytes. We demonstrate that these sympathetic fibers originate from the celiac ganglia, which are activated by cold challenge. Sympathetic-specific deletion of TrkA receptor or pharmacologic ablation by 6-hydroxydopamine abolishes these intra-adipose arborizations and, as a result, cold-induced beiging of inguinal WAT. Furthermore, we find that local sympathetic arborizations function through beta-adrenergic receptors in this beiging process. These findings uncover an essential link connecting efferent neural signals with metabolism of individual adipocytes.

    更新日期:2017-09-15
  • Intermittent Fasting Promotes White Adipose Browning and Decreases Obesity by Shaping the Gut Microbiota
    Cell Metab. (IF 18.164) Pub Date : 2017-09-14
    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
    更新日期:2017-09-15
  • A Predictive Model for Selective Targeting of the Warburg Effect through GAPDH Inhibition with a Natural Product
    Cell Metab. (IF 18.164) Pub Date : 2017-09-14
    Maria V. Liberti, Ziwei Dai, Suzanne E. Wardell, Joshua A. Baccile, Xiaojing Liu, Xia Gao, Robert Baldi, Mahya Mehrmohamadi, Marc O. Johnson, Neel S. Madhukar, Alexander A. Shestov, Iok I. Christine Chio, Olivier Elemento, Jeffrey C. Rathmell, Frank C. Schroeder, Donald P. McDonnell, Jason W. Locasale
    更新日期:2017-09-15
  • Dense Intra-adipose Sympathetic Arborizations Are Essential for Cold-Induced Beiging of Mouse White Adipose Tissue
    Cell Metab. (IF 18.164) Pub Date : 2017-09-14
    Haochen Jiang, Xiaofan Ding, Ying Cao, Huanhuan Wang, Wenwen Zeng
    更新日期:2017-09-15
  • Exploring Metabolic Configurations of Single Cells within Complex Tissue Microenvironments
    Cell Metab. (IF 18.164) Pub Date : 2017-09-07
    Anne Miller, Csörsz Nagy, Bernhard Knapp, Johannes Laengle, Elisabeth Ponweiser, Marion Groeger, Philipp Starkl, Michael Bergmann, Oswald Wagner, Arvand Haschemi

    Over the past years, plenty of evidence has emerged illustrating how metabolism supports many aspects of cellular function and how metabolic reprogramming can drive cell differentiation and fate. Here, we present a method to assess the metabolic configuration of single cells within their native tissue microenvironment via the visualization and quantification of multiple enzymatic activities measured at saturating substrate conditions combined with subsequent cell type identification. After careful validation of the approach and to demonstrate its potential, we assessed the intracellular metabolic configuration of different human immune cell populations in healthy and tumor colon tissue. Additionally, we analyzed the intercellular metabolic relationship between cancer cells and cancer-associated fibroblasts in a breast cancer tissue array. This study demonstrates that the determination of metabolic configurations in single cells could be a powerful complementary tool for every researcher interested to study metabolic networksin situ.

    更新日期:2017-09-07
  • Pancreatic β Cell Regeneration as a Possible Therapy for Diabetes
    Cell Metab. (IF 18.164) Pub Date : 2017-09-07
    Cristina Aguayo-Mazzucato, Susan Bonner-Weir

    Diabetes is the result of having inadequate supply of functional insulin-producing β cells. Two possible approaches for replenishing the β cells are: (1) replacement by transplanting cadaveric islets or β cells derived from human embryonic stem cells/induced pluripotent stem cells and (2) induction of endogenous regeneration. This review focuses on endogenous regeneration, which can follow two pathways: enhanced replication of existing β cells and formation of new β cells from cells not expressing insulin, either by conversion from a differentiated cell type (transdifferentiation) or differentiation from progenitors (neogenesis). Exciting progress on both pathways suggest that regeneration may have therapeutic promise.

    更新日期:2017-09-07
  • Exploring Metabolic Configurations of Single Cells within Complex Tissue Microenvironments
    Cell Metab. (IF 18.164) Pub Date : 2017-09-07
    Anne Miller, Csörsz Nagy, Bernhard Knapp, Johannes Laengle, Elisabeth Ponweiser, Marion Groeger, Philipp Starkl, Michael Bergmann, Oswald Wagner, Arvand Haschemi
    更新日期:2017-09-07
  • Pancreatic β Cell Regeneration as a Possible Therapy for Diabetes
    Cell Metab. (IF 18.164) Pub Date : 2017-09-07
    Cristina Aguayo-Mazzucato, Susan Bonner-Weir
    更新日期:2017-09-07
  • Meds Modify Microbiome, Mediating Their Effects
    Cell Metab. (IF 18.164) Pub Date : 2017-09-05
    Nicole M. Koropatkin, Eric C. Martens

    The mechanisms of action of some common medications remain unknown but, in some cases, may involve the microorganisms within us. A new study by Wu et al. (2017) provides evidence that the type 2 diabetes drug metformin alters the gut microbiota, which in turn may mediate some of the drug’s effects.

    更新日期:2017-09-05
  • Women in Metabolism: The Next Generation
    Cell Metab. (IF 18.164) Pub Date : 2017-09-05
    更新日期:2017-09-05
  • Disentangling High Fat, Low Carb, and Healthy Aging
    Cell Metab. (IF 18.164) Pub Date : 2017-09-05
    Holly M. Brown-Borg

    Dietary interventions are simple, non-invasive tools that can be utilized to improve health and lifespan. In this issue, Roberts et al. (2017) and Newman et al. (2017) reveal the physiological benefits of feeding mice ketogenic diets and suggest different underlying mechanisms that may promote healthy aging.

    更新日期:2017-09-05
  • The Liver as a Hub in Thermogenesis
    Cell Metab. (IF 18.164) Pub Date : 2017-09-05
    Nada A. Abumrad
    更新日期:2017-09-05
  • Distinct Circadian Signatures in Liver and Gut Clocks Revealed by Ketogenic Diet
    Cell Metab. (IF 18.164) Pub Date : 2017-09-05
    Paola Tognini, Mari Murakami, Yu Liu, Kristin L. Eckel-Mahan, John C. Newman, Eric Verdin, Pierre Baldi, Paolo Sassone-Corsi
    更新日期:2017-09-05
  • Persistence of Pancreatic Insulin mRNA Expression and Proinsulin Protein in Type 1 Diabetes Pancreata
    Cell Metab. (IF 18.164) Pub Date : 2017-09-05
    Clive Wasserfall, Harry S. Nick, Martha Campbell-Thompson, Dawn Beachy, Leena Haataja, Irina Kusmartseva, Amanda Posgai, Maria Beery, Christopher Rhodes, Ezio Bonifacio, Peter Arvan, Mark Atkinson
    更新日期:2017-09-05
  • Cell-Intrinsic Glycogen Metabolism Supports Early Glycolytic Reprogramming Required for Dendritic Cell Immune Responses
    Cell Metab. (IF 18.164) Pub Date : 2017-09-05
    Phyu M. Thwe, Leonard Pelgrom, Rachel Cooper, Saritha Beauchamp, Julie A. Reisz, Angelo D’Alessandro, Bart Everts, Eyal Amiel
    更新日期:2017-09-05
  • Acetyl CoA Carboxylase Inhibition Reduces Hepatic Steatosis but Elevates Plasma Triglycerides in Mice and Humans: A Bedside to Bench Investigation
    Cell Metab. (IF 18.164) Pub Date : 2017-09-05
    Chai-Wan Kim, Carol Addy, Jun Kusunoki, Norma N. Anderson, Stanislaw Deja, Xiaorong Fu, Shawn C. Burgess, Cai Li, Marcie Ruddy, Manu Chakravarthy, Steve Previs, Stuart Milstein, Kevin Fitzgerald, David E. Kelley, Jay D. Horton
    更新日期:2017-09-05
  • A Stat6/Pten Axis Links Regulatory T Cells with Adipose Tissue Function
    Cell Metab. (IF 18.164) Pub Date : 2017-09-05
    Stefanie Kälin, Maike Becker, Verena B. Ott, Isabelle Serr, Fabian Hosp, Mohammad M.H. Mollah, Susanne Keipert, Daniel Lamp, Francoise Rohner-Jeanrenaud, Victoria K. Flynn, Martin G. Scherm, Lucas F.R. Nascimento, Katharina Gerlach, Vanessa Popp, Sarah Dietzen, Tobias Bopp, Purna Krishnamurthy, Mark H. Kaplan, Manuel Serrano, Stephen C. Woods, Philipp Tripal, Ralf Palmisano, Martin Jastroch, Matthias Blüher, Christian Wolfrum, Benno Weigmann, Anette-Gabriele Ziegler, Matthias Mann, Matthias H. Tschöp, Carolin Daniel
    更新日期:2017-09-05
  • Global Analysis of Plasma Lipids Identifies Liver-Derived Acylcarnitines as a Fuel Source for Brown Fat Thermogenesis
    Cell Metab. (IF 18.164) Pub Date : 2017-09-05
    Judith Simcox, Gisela Geoghegan, John Alan Maschek, Claire L. Bensard, Marzia Pasquali, Ren Miao, Sanghoon Lee, Lei Jiang, Ian Huck, Erin E. Kershaw, Anthony J. Donato, Udayan Apte, Nicola Longo, Jared Rutter, Renate Schreiber, Rudolf Zechner, James Cox, Claudio J. Villanueva
    更新日期:2017-09-05
  • A Ketogenic Diet Extends Longevity and Healthspan in Adult Mice
    Cell Metab. (IF 18.164) Pub Date : 2017-09-05
    Megan N. Roberts, Marita A. Wallace, Alexey A. Tomilov, Zeyu Zhou, George R. Marcotte, Dianna Tran, Gabriella Perez, Elena Gutierrez-Casado, Shinichiro Koike, Trina A. Knotts, Denise M. Imai, Stephen M. Griffey, Kyoungmi Kim, Kevork Hagopian, Fawaz G. Haj, Keith Baar, Gino A. Cortopassi, Jon J. Ramsey, Jose Alberto Lopez-Dominguez
    更新日期:2017-09-05
  • Ketogenic Diet Reduces Midlife Mortality and Improves Memory in Aging Mice
    Cell Metab. (IF 18.164) Pub Date : 2017-09-05
    John C. Newman, Anthony J. Covarrubias, Minghao Zhao, Xinxing Yu, Philip Gut, Che-Ping Ng, Yu Huang, Saptarsi Haldar, Eric Verdin
    更新日期:2017-09-05
  • A Hypothalamic Phosphatase Switch Coordinates Energy Expenditure with Feeding
    Cell Metab. (IF 18.164) Pub Date : 2017-09-05
    Garron T. Dodd, Zane B. Andrews, Stephanie E. Simonds, Natalie J. Michael, Michael DeVeer, Jens C. Brüning, David Spanswick, Michael A. Cowley, Tony Tiganis
    更新日期:2017-09-05
  • Nonalcoholic Fatty Liver Disease as a Nexus of Metabolic and Hepatic Diseases
    Cell Metab. (IF 18.164) Pub Date : 2017-08-31
    Varman T. Samuel, Gerald I. Shulman

    NAFLD is closely linked with hepatic insulin resistance. Accumulation of hepatic diacylglycerol activates PKC-ε, impairing insulin receptor activation and insulin-stimulated glycogen synthesis. Peripheral insulin resistance indirectly influences hepatic glucose and lipid metabolism by increasing flux of substrates that promote lipogenesis (glucose and fatty acids) and gluconeogenesis (glycerol and fatty acid-derived acetyl-CoA, an allosteric activator of pyruvate carboxylase). Weight loss with diet or bariatric surgery effectively treats NAFLD, but drugs specifically approved for NAFLD are not available. Some new pharmacological strategies act broadly to alter energy balance or influence pathways that contribute to NAFLD (e.g., agonists for PPAR γ, PPAR α/δ, FXR and analogs for FGF-21, and GLP-1). Others specifically inhibit key enzymes involved in lipid synthesis (e.g., mitochondrial pyruvate carrier, acetyl-CoA carboxylase, stearoyl-CoA desaturase, and monoacyl- and diacyl-glycerol transferases). Finally, a novel class of liver-targeted mitochondrial uncoupling agents increases hepatocellular energy expenditure, reversing the metabolic and hepatic complications of NAFLD.

    更新日期:2017-08-31
  • Nonalcoholic Fatty Liver Disease as a Nexus of Metabolic and Hepatic Diseases
    Cell Metab. (IF 18.164) Pub Date : 2017-08-31
    Varman T. Samuel, Gerald I. Shulman
    更新日期:2017-08-31
  • Creatine Fuels the Thermic Effect of Feeding
    Cell Metab. (IF 18.164) Pub Date : 2017-08-24
    Alan R. Saltiel

    The current obesity epidemic has focused a great deal of attention on cellular pathways of energy expenditure. While a crucial part of this process is diet-induced thermogenesis, the underlying mechanisms have remained unexplained. In this issue ofCell Metabolism, Kazak et al. (2017) describe a new thermogenic pathway in adipocytes that responds to diet overload, involving creatine cycling. These data suggest that this pathway might limit weight gain during overnutrition.

    更新日期:2017-08-24
  • Genetic Depletion of Adipocyte Creatine Metabolism Inhibits Diet-Induced Thermogenesis and Drives Obesity
    Cell Metab. (IF 18.164) Pub Date : 2017-08-24
    Lawrence Kazak, Edward T. Chouchani, Gina Z. Lu, Mark P. Jedrychowski, Curtis J. Bare, Amir I. Mina, Manju Kumari, Song Zhang, Ivan Vuckovic, Dina Laznik-Bogoslavski, Petras Dzeja, Alexander S. Banks, Evan D. Rosen, Bruce M. Spiegelman

    Diet-induced thermogenesis is an important homeostatic mechanism that limits weight gain in response to caloric excess and contributes to the relative stability of body weight in most individuals. We previously demonstrated that creatine enhances energy expenditure through stimulation of mitochondrial ATP turnover, but the physiological role and importance of creatine energetics in adipose tissue have not been explored. Here, we have inactivated the first and rate-limiting enzyme of creatine biosynthesis, glycine amidinotransferase (GATM), selectively in fat (Adipo-Gatm KO). Adipo-Gatm KO mice are prone to diet-induced obesity due to the suppression of elevated energy expenditure that occurs in response to high-calorie feeding. This is paralleled by a blunted capacity for β3-adrenergic activation of metabolic rate, which is rescued by dietary creatine supplementation. These results provide strong in vivo genetic support for a role of GATM and creatine metabolism in energy expenditure, diet-induced thermogenesis, and defense against diet-induced obesity.

    更新日期:2017-08-24
  • The FGF21-CCL11 Axis Mediates Beiging of White Adipose Tissues by Coupling Sympathetic Nervous System to Type 2 Immunity
    Cell Metab. (IF 18.164) Pub Date : 2017-08-24
    Zhe Huang, Ling Zhong, Jimmy Tsz Hang Lee, Jialiang Zhang, Donghai Wu, Leiluo Geng, Yu Wang, Chi-Ming Wong, Aimin Xu

    Type 2 cytokines are important signals triggering biogenesis of thermogenic beige adipocytes in white adipose tissue (WAT) during cold acclimation. However, how cold activates type 2 immunity in WAT remains obscure. Here we show that cold-induced type 2 immune responses and beiging in subcutaneous WAT (scWAT) are abrogated in mice with adipose-selective ablation of FGF21 or its co-receptor β-Klotho, whereas such impairments are reversed by replenishment with chemokine CCL11. Mechanistically, FGF21 acts on adipocytes in an autocrine manner to promote the expression and secretion of CCL11 via activation of ERK1/2, which drives recruitment of eosinophils into scWAT, leading to increases in accumulation of M2 macrophages, and proliferation and commitment of adipocyte precursors into beige adipocytes. These FGF21-elicited type 2 immune responses and beiging are blocked by CCL11 neutralization. Thus, the adipose-derived FGF21-CCL11 axis triggers cold-induced beiging and thermogenesis by coupling sympathetic nervous system to activation of type 2 immunity in scWAT.

    更新日期:2017-08-24
  • The Lymphatic Vasculature: Its Role in Adipose Metabolism and Obesity
    Cell Metab. (IF 18.164) Pub Date : 2017-08-24
    Noelia Escobedo, Guillermo Oliver

    Obesity is a key risk factor for metabolic and cardiovascular diseases, and although we understand the mechanisms regulating weight and energy balance, the causes of some forms of obesity remain enigmatic. Despite the well-established connections between lymphatics and lipids, and the fact that intestinal lacteals play key roles in dietary fat absorption, the function of the lymphatic vasculature in adipose metabolism has only recently been recognized. It is well established that angiogenesis is tightly associated with the outgrowth of adipose tissue, as expanding adipose tissue requires increased nutrient supply from blood vessels. Results supporting a crosstalk between lymphatic vessels and adipose tissue, and linking lymphatic function with metabolic diseases, obesity, and adipose tissue, also started to accumulate in the last years. Here we review our current knowledge of the mechanisms by which defective lymphatics contribute to obesity and fat accumulation in mouse models, as well as our understanding of the lymphatic-adipose tissue relationship.

    更新日期:2017-08-24
  • Creatine Fuels the Thermic Effect of Feeding
    Cell Metab. (IF 18.164) Pub Date : 2017-08-24
    Alan R. Saltiel

    The current obesity epidemic has focused a great deal of attention on cellular pathways of energy expenditure. While a crucial part of this process is diet-induced thermogenesis, the underlying mechanisms have remained unexplained. In this issue ofCell Metabolism, Kazak et al. (2017) describe a new thermogenic pathway in adipocytes that responds to diet overload, involving creatine cycling. These data suggest that this pathway might limit weight gain during overnutrition.

    更新日期:2017-08-24
  • Genetic Depletion of Adipocyte Creatine Metabolism Inhibits Diet-Induced Thermogenesis and Drives Obesity
    Cell Metab. (IF 18.164) Pub Date : 2017-08-24
    Lawrence Kazak, Edward T. Chouchani, Gina Z. Lu, Mark P. Jedrychowski, Curtis J. Bare, Amir I. Mina, Manju Kumari, Song Zhang, Ivan Vuckovic, Dina Laznik-Bogoslavski, Petras Dzeja, Alexander S. Banks, Evan D. Rosen, Bruce M. Spiegelman
    更新日期:2017-08-24
  • The FGF21-CCL11 Axis Mediates Beiging of White Adipose Tissues by Coupling Sympathetic Nervous System to Type 2 Immunity
    Cell Metab. (IF 18.164) Pub Date : 2017-08-24
    Zhe Huang, Ling Zhong, Jimmy Tsz Hang Lee, Jialiang Zhang, Donghai Wu, Leiluo Geng, Yu Wang, Chi-Ming Wong, Aimin Xu
    更新日期:2017-08-24
  • The Lymphatic Vasculature: Its Role in Adipose Metabolism and Obesity
    Cell Metab. (IF 18.164) Pub Date : 2017-08-24
    Noelia Escobedo, Guillermo Oliver
    更新日期:2017-08-24
  • Regulation of Stem Cell Aging by Metabolism and Epigenetics
    Cell Metab. (IF 18.164) Pub Date : 2017-08-17
    Ruotong Ren, Alejandro Ocampo, Guang-Hui Liu, Juan Carlos Izpisua Belmonte

    Stem cell aging and exhaustion are considered important drivers of organismal aging. Age-associated declines in stem cell function are characterized by metabolic and epigenetic changes. Understanding the mechanisms underlying these changes will likely reveal novel therapeutic targets for ameliorating age-associated phenotypes and for prolonging human healthspan. Recent studies have shown that metabolism plays an important role in regulating epigenetic modifications and that this regulation dramatically affects the aging process. This review focuses on current knowledge regarding the mechanisms of stem cell aging, and the links between cellular metabolism and epigenetic regulation. In addition, we discuss how these interactions sense and respond to environmental stress in order to maintain stem cell homeostasis, and how environmental stimuli regulate stem cell function. Additionally, we highlight recent advances in the development of therapeutic strategies to rejuvenate dysfunctional aged stem cells.

    更新日期:2017-08-24
  • Regulation of Stem Cell Aging by Metabolism and Epigenetics
    Cell Metab. (IF 18.164) Pub Date : 2017-08-17
    Ruotong Ren, Alejandro Ocampo, Guang-Hui Liu, Juan Carlos Izpisua Belmonte
    更新日期:2017-08-24
  • Insulin Regulation of Proteostasis and Clinical Implications
    Cell Metab. (IF 18.164) Pub Date : 2017-07-13
    Haleigh A. James, Brian T. O'Neill, K. Sreekumaran Nair
    更新日期:2017-08-24
  • Burning Fat and Building Bone by FSH Blockade
    Cell Metab. (IF 18.164) Pub Date : 2017-08-01
    Carlos Henrique Sponton, Shingo Kajimura
    更新日期:2017-08-24
  • What’s So Special about FGF19—Unique Effects Reported on Skeletal Muscle Mass and Function
    Cell Metab. (IF 18.164) Pub Date : 2017-08-01
    David J. Glass

    In a recent study published inNature Medicine, Benoit et al. (2017) reported unique effects of FGF19 on mouse skeletal muscle: FGF19 induced skeletal muscle hypertrophy and blocked muscle atrophy, acting via FGF receptors and ßKlotho, while a related FGF21 hormone was ineffective.

    更新日期:2017-08-24
  • Long-Term Cold Adaptation Does Not Require FGF21 or UCP1
    Cell Metab. (IF 18.164) Pub Date : 2017-08-01
    Susanne Keipert, Maria Kutschke, Mario Ost, Thomas Schwarzmayr, Evert M. van Schothorst, Daniel Lamp, Laura Brachthäuser, Isabel Hamp, Sithandiwe E. Mazibuko, Sonja Hartwig, Stefan Lehr, Elisabeth Graf, Oliver Plettenburg, Frauke Neff, Matthias H. Tschöp, Martin Jastroch
    更新日期:2017-08-24
  • Holding Onto Youth
    Cell Metab. (IF 18.164) Pub Date : 2017-08-01
    Alain Dagher, Bratislav Misic

    Aerobic glycolysis (AG), the synthesis of lactate despite the presence of oxygen, has been implicated in the growth of cancer cells, synaptic development, and brain plasticity. In this issue ofCell Metabolism, Goyal et al. (2017) demonstrate that AG declines with age in the human brain, disappearing almost completely by age 60.

    更新日期:2017-08-24
  • Once Blind, Now We See GLP-1 Molecular Action
    Cell Metab. (IF 18.164) Pub Date : 2017-08-01
    John P. Mayer, Matthias H. Tschöp, Richard D. DiMarchi
    更新日期:2017-08-24
  • A Hypothalamic Phosphatase Switch Coordinates Energy Expenditure with Feeding
    Cell Metab. (IF 18.164) Pub Date : 2017-08-01
    Garron T. Dodd, Zane B. Andrews, Stephanie E. Simonds, Natalie J. Michael, Michael DeVeer, Jens C. Brüning, David Spanswick, Michael A. Cowley, Tony Tiganis
    更新日期:2017-08-24
  • Triglyceride Synthesis by DGAT1 Protects Adipocytes from Lipid-Induced ER Stress during Lipolysis
    Cell Metab. (IF 18.164) Pub Date : 2017-08-01
    Chandramohan Chitraju, Niklas Mejhert, Joel T. Haas, L. Grisell Diaz-Ramirez, Carrie A. Grueter, Jason E. Imbriglio, Shirly Pinto, Suneil K. Koliwad, Tobias C. Walther, Robert V. Farese
    更新日期:2017-08-24
  • The Sustained Effects of a Dual GIP/GLP-1 Receptor Agonist, NNC0090-2746, in Patients with Type 2 Diabetes
    Cell Metab. (IF 18.164) Pub Date : 2017-08-01
    Juan Pablo Frias, Edward J. Bastyr, Louis Vignati, Matthias H. Tschöp, Christophe Schmitt, Klara Owen, Rune Haubo Christensen, Richard D. DiMarchi
    更新日期:2017-08-24
  • Loss of Brain Aerobic Glycolysis in Normal Human Aging
    Cell Metab. (IF 18.164) Pub Date : 2017-08-01
    Manu S. Goyal, Andrei G. Vlassenko, Tyler M. Blazey, Yi Su, Lars E. Couture, Tony J. Durbin, Randall J. Bateman, Tammie L.-S. Benzinger, John C. Morris, Marcus E. Raichle
    更新日期:2017-08-24
  • Acetyl CoA Carboxylase Inhibition Reduces Hepatic Steatosis but Elevates Plasma Triglycerides in Mice and Humans: A Bedside to Bench Investigation
    Cell Metab. (IF 18.164) Pub Date : 2017-08-01
    Chai-Wan Kim, Carol Addy, Jun Kusunoki, Norma N. Anderson, Stanislaw Deja, Xiaorong Fu, Shawn C. Burgess, Cai Li, Manu Chakravarthy, Steve Previs, Stuart Milstein, Kevin Fitzgerald, David E. Kelley, Jay D. Horton
    更新日期:2017-08-24
  • Causes, Characteristics, and Consequences of Metabolically Unhealthy Normal Weight in Humans
    Cell Metab. (IF 18.164) Pub Date : 2017-08-01
    Norbert Stefan, Fritz Schick, Hans-Ulrich Häring
    更新日期:2017-08-24
  • mTORC1 Regulates Mitochondrial Integrated Stress Response and Mitochondrial Myopathy Progression
    Cell Metab. (IF 18.164) Pub Date : 2017-08-01
    Nahid A. Khan, Joni Nikkanen, Shuichi Yatsuga, Christopher Jackson, Liya Wang, Swagat Pradhan, Riikka Kivelä, Alberto Pessia, Vidya Velagapudi, Anu Suomalainen
    更新日期:2017-08-24
  • Plasma Mannose Levels Are Associated with Incident Type 2 Diabetes and Cardiovascular Disease
    Cell Metab. (IF 18.164) Pub Date : 2017-08-01
    Adil Mardinoglu, Alena Stančáková, Luca A. Lotta, Johanna Kuusisto, Jan Boren, Matthias Blüher, Nicholas J. Wareham, Ele Ferrannini, Per Henrik Groop, Markku Laakso, Claudia Langenberg, Ulf Smith

    Plasma mannose levels are elevated in subjects with insulin resistance independently of obesity. Here, we found that elevated plasma mannose levels are strong markers of future risk of several chronic diseases including T2D, CVD, and albuminuria, and that it may contribute to their development rather than just being a novel biomarker.

    更新日期:2017-08-24
  • DNA-PK Promotes the Mitochondrial, Metabolic, and Physical Decline that Occurs During Aging
    Cell Metab. (IF 18.164) Pub Date : 2017-08-01
    Sung-Jun Park, Oksana Gavrilova, Alexandra L. Brown, Jamie E. Soto, Shannon Bremner, Jeonghan Kim, Xihui Xu, Shutong Yang, Jee-Hyun Um, Lauren G. Koch, Steven L. Britton, Richard L. Lieber, Andrew Philp, Keith Baar, Steven G. Kohama, E. Dale Abel, Myung K. Kim, Jay H. Chung

    (Cell Metabolism 25, 1135–1146; May 2, 2017)

    更新日期:2017-08-24
  • Sweet Sixteenth for ChREBP: Established Roles and Future Goals
    Cell Metab. (IF 18.164) Pub Date : 2017-08-01
    Aya Abdul-Wahed, Sandra Guilmeau, Catherine Postic
    更新日期:2017-08-24
  • Increased Total mtDNA Copy Number Cures Male Infertility Despite Unaltered mtDNA Mutation Load
    Cell Metab. (IF 18.164) Pub Date : 2017-08-01
    Min Jiang, Timo Eino Sakari Kauppila, Elisa Motori, Xinping Li, Ilian Atanassov, Kat Folz-Donahue, Nina Anna Bonekamp, Sara Albarran-Gutierrez, James Bruce Stewart, Nils-Göran Larsson
    更新日期:2017-08-24
  • Chronic Sucralose or L-Glucose Ingestion Does Not Suppress Food Intake
    Cell Metab. (IF 18.164) Pub Date : 2017-08-01
    Qiao-Ping Wang, Stephen J. Simpson, Herbert Herzog, G. Gregory Neely

    Despite widespread consumption of non-nutritive sweeteners (NNSs), the impact of manipulating the perceived sweetness of food is unclear. Previously we reported that chronic consumption of the NNSs sucralose or L-glucose led to increased calories consumed post-exposure; however, a recent study suggested this effect occurs because NNSs acutely suppress food intake, leading to a caloric debt. Here we show that acute ingestion of sucralose in the context of a low-carbohydrate diet causes a pronounced increase in calories consumed. Moreover, neither sucralose nor L-glucose had a lasting effect on food intake during chronic exposure; however, both NNSs enhance food intake post-exposure. Together these data confirm that sucralose and L-glucose promote food intake under a variety of experimental conditions.

    更新日期:2017-08-24
  • The Dawn of the Age of Amino Acid Sensors for the mTORC1 Pathway
    Cell Metab. (IF 18.164) Pub Date : 2017-08-01
    Rachel L. Wolfson, David M. Sabatini
    更新日期:2017-08-24
  • Neuronal Stimulation Triggers Neuronal Glycolysis and Not Lactate Uptake
    Cell Metab. (IF 18.164) Pub Date : 2017-08-01
    Carlos Manlio Díaz-García, Rebecca Mongeon, Carolina Lahmann, Dorothy Koveal, Hannah Zucker, Gary Yellen
    更新日期:2017-08-24
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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