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    2349 results match your criteria Cell Metabolism [Journal]

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    AMPK: Sensing Glucose as well as Cellular Energy Status.
    Cell Metab 2017 Nov 15. Epub 2017 Nov 15.
    Division of Cell Signalling & Immunology, School of Life Sciences, University of Dundee, Dundee DD1 5EH, UK. Electronic address:
    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. Read More

    Brown Fat AKT2 Is a Cold-Induced Kinase that Stimulates ChREBP-Mediated De Novo Lipogenesis to Optimize Fuel Storage and Thermogenesis.
    Cell Metab 2017 Nov 15. Epub 2017 Nov 15.
    Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, MA 01605, USA. Electronic address:
    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. Read More

    CD38-NAD(+)Axis Regulates Immunotherapeutic Anti-Tumor T Cell Response.
    Cell Metab 2017 Nov 8. Epub 2017 Nov 8.
    Department of Surgery, Hollings Cancer Center, Medical University of South Carolina, Charleston, SC 29425, USA. Electronic address:
    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 established ex vivo culture conditions to generate hybrid Th1/17 cells, which persisted long-term in vivo while 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. Read More

    Mechanisms by which a Very-Low-Calorie Diet Reverses Hyperglycemia in a Rat Model of Type 2 Diabetes.
    Cell Metab 2017 Nov 8. Epub 2017 Nov 8.
    Department of Internal Medicine, Yale University School of Medicine, New Haven, CT 06520, USA; Department of Cellular & Molecular Physiology, Yale University School of Medicine, New Haven, CT 06520, USA; Howard Hughes Medical Institute, Yale University School of Medicine, New Haven, CT 06520, USA. Electronic address:
    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. Read More

    Advances in Hypoxia-Inducible Factor Biology.
    Cell Metab 2017 Nov 8. Epub 2017 Nov 8.
    Molecular Oncology Laboratories, Department of Oncology, University of Oxford, Weatherall Institute of Molecular Medicine, Oxford OX3 9DS, UK. Electronic address:
    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. Read More

    Resistance Is Futile: Targeting Mitochondrial Energetics and Metabolism to Overcome Drug Resistance in Cancer Treatment.
    Cell Metab 2017 Nov;26(5):705-707
    Inserm, Cancer Research Center of Toulouse, U1037, 31024 Toulouse, France; Université de Toulouse, 31300 Toulouse, France. Electronic address:
    Metabolism is a key regulator of cancer biology; however, its role in therapeutic resistance has remained largely unresolved. Several new studies disclose that mitochondrial metabolism and oxidative phosphorylation at least in part drive chemoresistance in cancer and thus have important implications for targeted and more effective chemotherapies. Read More

    Glial Cell Evolution: The Origins of a Lipid Store.
    Cell Metab 2017 Nov;26(5):701-702
    Institut für Neuro- and Verhaltensbiologie, University of Münster, Münster, Germany.
    In Drosophila, neuronal mitochondria that lack OXPHOS generate ROS-protective fatty acids and lipid droplets in associated glia. In this issue, Liu et al. (2017) demonstrate that neuronal lipid synthesis is driven by the glial lactate shuttle. Read More

    NFIL-trating the Host Circadian Rhythm-Microbes Fine-Tune the Epithelial Clock.
    Cell Metab 2017 Nov;26(5):699-700
    Department of Immunology, Weizmann Institute of Science, Rehovot 76100, Israel. Electronic address:
    The diurnal activities of the intestinal microbiota and its host are closely connected, but the nature of their circadian communication pathways remains obscure. Wang et al. (2017) have described a signaling circuit linking microbial sensing by the immune system to the epithelial clock, thereby orchestrating local and systemic lipid metabolism. Read More

    What Ignites UCP1?
    Cell Metab 2017 Nov;26(5):697-698
    Department of Molecular Biosciences, The Wenner-Gren Institute, Stockholm University, Stockholm, Sweden.
    We thought we knew how the heat-producing uncoupling protein 1 in brown adipose tissue was activated: by fatty acids released upon lipid droplet breakdown in the brown adipocytes. However, two studies in this issue (Schreiber et al., 2017; Shin et al. Read More

    Dealing with Consequences of Irreproducibility and Modifying the Published Literature: Retractions versus Revisions.
    Cell Metab 2017 Nov;26(5):695-696
    Department of Medicine and Neurobiology, Harvard Medical School, 220 Longwood Avenue, Goldenson 542, Boston, MA 02115, USA. Electronic address:
    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. Read More

    Dietary Restriction and AMPK Increase Lifespan via Mitochondrial Network and Peroxisome Remodeling.
    Cell Metab 2017 Oct 23. Epub 2017 Oct 23.
    Department of Genetics and Complex Diseases, Harvard T.H. Chan School of Public Health, Boston, MA 02115, USA. Electronic address:
    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 in C. Read More

    System-wide Benefits of Intermeal Fasting by Autophagy.
    Cell Metab 2017 Oct 24. Epub 2017 Oct 24.
    Department of Medicine, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Forchheimer 505D, Bronx, NY 10461, USA; Department of Molecular Pharmacology, Albert Einstein College of Medicine, Bronx, NY 10461, USA; Institute for Aging Research, Albert Einstein College of Medicine, Bronx, NY 10461, USA; Diabetes Research Center, Albert Einstein College of Medicine, Bronx, NY 10461, USA. Electronic address:
    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 as ad libitum controls but at two short windows early and late in the diurnal cycle. Read More

    Overlapping Brain Circuits for Homeostatic and Hedonic Feeding.
    Cell Metab 2017 Oct 26. Epub 2017 Oct 26.
    Department of Psychiatry, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA; Neuroscience Center, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA; Department of Cell Biology and Physiology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA. Electronic address:
    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. Read More

    Abrogating Mitochondrial Dynamics in Mouse Hearts Accelerates Mitochondrial Senescence.
    Cell Metab 2017 Oct 21. Epub 2017 Oct 21.
    Center for Pharmacogenomics, Department of Internal Medicine, Washington University School of Medicine, St. Louis, MO, USA. Electronic address:
    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. Read More

    Artemether Does Not Turn α Cells into β Cells.
    Cell Metab 2017 Nov 1. Epub 2017 Nov 1.
    Department of Neurobiology, Physiology & Behavior, College of Biological Sciences, University of California, Davis, CA 95616, USA; Department of Physiology and Membrane Biology, School of Medicine, University of California, Davis, CA 95616, USA. Electronic address:
    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. Read More

    17β-Estradiol Directly Lowers Mitochondrial Membrane Microviscosity and Improves Bioenergetic Function in Skeletal Muscle.
    Cell Metab 2017 Nov 1. Epub 2017 Nov 1.
    East Carolina Diabetes and Obesity Institute, East Carolina University, 115 Heart Drive, ECHI - Mail Stop 743, Greenville, NC 27834, USA; Department of Kinesiology, College of Health and Human Performance, East Carolina University, Greenville, NC 27834, USA; Department of Physiology, Brody School of Medicine, East Carolina University, Greenville, NC 27834, USA. Electronic address:
    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. Read More

    In Vivo Imaging of Glutamine Metabolism to the Oncometabolite 2-Hydroxyglutarate in IDH1/2 Mutant Tumors.
    Cell Metab 2017 Oct 16. Epub 2017 Oct 16.
    Department of Radiology, Memorial Sloan Kettering Cancer Center (MSKCC), New York, NY 10065, USA; Molecular Pharmacology Program, Memorial Sloan Kettering Cancer Center (MSKCC), New York, NY 10065, USA; Weill Cornell Medical College, New York, NY 10065, USA. Electronic address:
    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 access in vivo. Here, utilizing patient-derived chondrosarcoma cells harboring endogenous mutations in IDH1 and IDH2, we report that 2-HG can be rapidly generated from glutamine in vitro. Read More

    Molecular Mechanisms Linking Exercise to Cancer Prevention and Treatment.
    Cell Metab 2017 Oct 17. Epub 2017 Oct 17.
    Centre of Inflammation and Metabolism (CIM) and Centre for Physical Activity Research (CFAS), Rigshospitalet, Faculty of Health Science, University of Copenhagen, Copenhagen, Denmark.
    The benefits of exercise training for cancer patients are becoming increasingly evident. Physical exercise has been shown to reduce cancer incidence and inhibit tumor growth. Here we provide the status of the current molecular understanding of the effect of exercise on cancer. Read More

    Metformin Alters Upper Small Intestinal Microbiota that Impact a Glucose-SGLT1-Sensing Glucoregulatory Pathway.
    Cell Metab 2017 Oct 17. Epub 2017 Oct 17.
    Toronto General Hospital Research Institute, UHN, Toronto, ON M5G 1L7, Canada; Department of Physiology, University of Toronto, Toronto, ON M5S 1A8, Canada; Department of Medicine, University of Toronto, Toronto, ON M5S 1A8, Canada; Banting and Best Diabetes Centre, University of Toronto, Toronto, ON M5G 2C4, Canada. Electronic address:
    The gut microbiota alters energy homeostasis. In parallel, metformin regulates upper small intestinal sodium glucose cotransporter-1 (SGLT1), but whether changes of the microbiota or SGLT1-dependent pathways in the upper small intestine mediate metformin action is unknown. Here we report that upper small intestinal glucose sensing triggers an SGLT1-dependent pathway to lower glucose production in rodents. Read More

    Acetyl-CoA Carboxylase 1-Dependent Protein Acetylation Controls Breast Cancer Metastasis and Recurrence.
    Cell Metab 2017 Oct 12. Epub 2017 Oct 12.
    Institute for Diabetes and Cancer, Helmholtz Center Munich, Neuherberg, Germany; Joint Heidelberg-IDC Translational Diabetes Program, Inner Medicine 1, Heidelberg University Hospital, Heidelberg, Germany; Technical University Munich, 85764 Neuherberg, Germany; Deutsches Zentrum für Diabetesforschung, 85764 Neuherberg, Germany. Electronic address:
    Breast tumor recurrence and metastasis represent the main causes of cancer-related death in women, and treatments are still lacking. Here, we define the lipogenic enzyme acetyl-CoA carboxylase (ACC) 1 as a key player in breast cancer metastasis. ACC1 phosphorylation was increased in invading cells both in murine and human breast cancer, serving as a point of convergence for leptin and transforming growth factor (TGF) β signaling. Read More

    CANTOS Ushers in a New Calculus of Inflammasome Targeting for Vascular Protection-and Maybe More.
    Cell Metab 2017 Nov 19;26(5):703-705. Epub 2017 Oct 19.
    Cardiovascular Division, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
    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. Read More

    PGC-1α Promotes Breast Cancer Metastasis and Confers Bioenergetic Flexibility against Metabolic Drugs.
    Cell Metab 2017 Nov 5;26(5):778-787.e5. Epub 2017 Oct 5.
    Department of Biochemistry, McGill University, Montreal, QC H3G 1Y6, Canada; Goodman Cancer Research Centre, McGill University, Montreal, QC H3G 1Y6, Canada. Electronic address:
    Metabolic adaptations play a key role in fueling tumor growth. However, less is known regarding the metabolic changes that promote cancer progression to metastatic disease. Herein, we reveal that breast cancer cells that preferentially metastasize to the lung or bone display relatively high expression of PGC-1α compared with those that metastasize to the liver. Read More

    Citrobacter rodentium Subverts ATP Flux and Cholesterol Homeostasis in Intestinal Epithelial Cells In Vivo.
    Cell Metab 2017 Nov 5;26(5):738-752.e6. Epub 2017 Oct 5.
    MRC Centre for Molecular Bacteriology and Infection, Department of Life Sciences, Imperial College London, London, UK. Electronic address:
    The intestinal epithelial cells (IECs) that line the gut form a robust line of defense against ingested pathogens. We investigated the impact of infection with the enteric pathogen Citrobacter rodentium on mouse IEC metabolism using global proteomic and targeted metabolomics and lipidomics. The major signatures of the infection were upregulation of the sugar transporter Sglt4, aerobic glycolysis, and production of phosphocreatine, which mobilizes cytosolic energy. Read More

    FGF19, FGF21, and an FGFR1/β-Klotho-Activating Antibody Act on the Nervous System to Regulate Body Weight and Glycemia.
    Cell Metab 2017 Nov 5;26(5):709-718.e3. Epub 2017 Oct 5.
    Department of Pharmacology, UT Southwestern Medical Center, Dallas, TX 75390, USA; Howard Hughes Medical Institute, UT Southwestern Medical Center, Dallas, TX 75390, USA. Electronic address:
    Despite the different physiologic functions of FGF19 and FGF21 as hormonal regulators of fed and fasted metabolism, their pharmacologic administration causes similar increases in energy expenditure, weight loss, and enhanced insulin sensitivity in obese animals. Here, in genetic loss-of-function studies of the shared co-receptor β-Klotho, we show that these pharmacologic effects are mediated through a common, tissue-specific pathway. Surprisingly, FGF19 and FGF21 actions in liver and adipose tissue are not required for their longer-term weight loss and glycemic effects. Read More

    Lipolysis in Brown Adipocytes Is Not Essential for Cold-Induced Thermogenesis in Mice.
    Cell Metab 2017 Nov 5;26(5):764-777.e5. Epub 2017 Oct 5.
    Department of Animal and Avian Sciences, University of Maryland, College Park, MD 20742, USA; Center for Molecular and Translational Medicine, Institute for Biomedical Sciences, Georgia State University, Atlanta, GA 30303, USA. Electronic address:
    Lipid droplet (LD) lipolysis in brown adipose tissue (BAT) is generally considered to be required for cold-induced nonshivering thermogenesis. Here, we show that mice lacking BAT Comparative Gene Identification-58 (CGI-58), a lipolytic activator essential for the stimulated LD lipolysis, have normal thermogenic capacity and are not cold sensitive. Relative to littermate controls, these animals had higher body temperatures when they were provided food during cold exposure. Read More

    Cold-Induced Thermogenesis Depends on ATGL-Mediated Lipolysis in Cardiac Muscle, but Not Brown Adipose Tissue.
    Cell Metab 2017 Nov 5;26(5):753-763.e7. Epub 2017 Oct 5.
    Institute of Molecular Biosciences, University of Graz, 8010 Graz, Austria; BioTechMed-Graz, 8010 Graz, Austria. Electronic address:
    Fatty acids (FAs) activate and fuel UCP1-mediated non-shivering thermogenesis (NST) in brown adipose tissue (BAT). Release of FAs from intracellular fat stores by adipose triglyceride lipase (ATGL) is considered a key step in NST. Accordingly, the severe cold intolerance of global ATGL knockout (AKO) mice has been attributed to defective BAT lipolysis. Read More

    ATF4-Induced Metabolic Reprograming Is a Synthetic Vulnerability of the p62-Deficient Tumor Stroma.
    Cell Metab 2017 Sep 27. Epub 2017 Sep 27.
    Cancer Metabolism and Signaling Networks Program, Sanford Burnham Prebys Medical Discovery Institute, 10901 North Torrey Pines Road, La Jolla, CA 92037, USA. Electronic address:
    Tumors undergo nutrient stress and need to reprogram their metabolism to survive. The stroma may play a critical role in this process by providing nutrients to support the epithelial compartment of the tumor. Here we show that p62 deficiency in stromal fibroblasts promotes resistance to glutamine deprivation by the direct control of ATF4 stability through its p62-mediated polyubiquitination. Read More

    MYC and MCL1 Cooperatively Promote Chemotherapy-Resistant Breast Cancer Stem Cells via Regulation of Mitochondrial Oxidative Phosphorylation.
    Cell Metab 2017 Oct;26(4):633-647.e7
    Department of Medicine, Vanderbilt University Medical Center, Nashville, TN 37232, USA; Breast Cancer Research Program, Vanderbilt-Ingram Cancer Center, Vanderbilt University Medical Center, Nashville, TN 37232, USA; Department of Cancer Biology, Vanderbilt University Medical Center, Nashville, TN 37232, USA. Electronic address:
    Most patients with advanced triple-negative breast cancer (TNBC) develop drug resistance. MYC and MCL1 are frequently co-amplified in drug-resistant TNBC after neoadjuvant chemotherapy. Herein, we demonstrate that MYC and MCL1 cooperate in the maintenance of chemotherapy-resistant cancer stem cells (CSCs) in TNBC. Read More

    Improvement of Insulin Sensitivity after Lean Donor Feces in Metabolic Syndrome Is Driven by Baseline Intestinal Microbiota Composition.
    Cell Metab 2017 Oct;26(4):611-619.e6
    Department of Vascular Medicine, Academic Medical Center, University of Amsterdam, 1105 AZ Amsterdam, the Netherlands; Top Institute of Food and Nutrition, 6700 AN Wageningen, the Netherlands; Department of Internal Medicine, VUMC, Free University, Amsterdam, the Netherlands; Wallenberg Laboratory, Sahlgrenska Hospital, University of Gothenburg, Gothenburg, Sweden. Electronic address:
    The intestinal microbiota has been implicated in insulin resistance, although evidence regarding causality in humans is scarce. We therefore studied the effect of lean donor (allogenic) versus own (autologous) fecal microbiota transplantation (FMT) to male recipients with the metabolic syndrome. Whereas we did not observe metabolic changes at 18 weeks after FMT, insulin sensitivity at 6 weeks after allogenic FMT was significantly improved, accompanied by altered microbiota composition. Read More

    Antigen-Specific Peptide Immunotherapy for Type 1 Diabetes: Proof of Safety, Hope for Efficacy.
    Cell Metab 2017 Oct;26(4):595-597
    Type 1 Diabetes Research Center, Novo Nordisk, Seattle, WA, USA; Type 1 Diabetes Center, La Jolla Institute for Allergy and Immunology, La Jolla, CA 92014, USA. Electronic address:
    Antigen-specific immunotherapy has long been hailed as the ideal disease-modifying approach for type 1 diabetes, both for disease prevention and reversal. A small phase 1 trial now demonstrates safety of a peptide-based treatment in recently diagnosed adults. Read More

    Slowing Down Aging.
    Cell Metab 2017 Oct;26(4):592-593
    Department of Genetics, Harvard Medical School, Boston, MA 02115, USA. Electronic address:
    The hypothalamus plays a key role in coordinating the physiological changes that underlie mammalian aging. In a recent issue of Nature, Cai and colleagues (2017) shed new light on the mechanism of this effect by providing evidence that hypothalamic stem cells may regulate aging through the release of microRNAs in exosomes. Read More

    TREM2: Keeping Microglia Fit during Good Times and Bad.
    Cell Metab 2017 Oct;26(4):590-591
    F.M. Kirby Neurobiology Center, Boston Children's Hospital and Harvard Medical School, Boston, MA 02115, USA; Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA. Electronic address:
    Microglia are the macrophages of the brain and play an important role in Alzheimer's disease (AD). In Cell, Ulland et al. (2017) recently reported that mutations in TREM2, a protein implicated in AD, disrupt microglial energy state and function, thus sabotaging the microglia's ability to defend the brain against amyloid plaques. Read More

    The Burgeoning World of Immunometabolites: Th17 Cells Take Center Stage.
    Cell Metab 2017 Oct;26(4):588-590
    Immunobiology, Department of Biomedicine, University of Basel and University Hospital Basel, Basel, Switzerland. Electronic address:
    Dysregulation of the Th17/Treg balance is a key driver of autoimmunity. A new study by Xu et al. (2017) has revealed that small-molecule inhibition of 2-hydroxyglutarate synthesis skews Th17 differentiation to the Treg lineage, which is protective against autoimmune inflammation. Read More

    Dietary Carbohydrates Impair Healthspan and Promote Mortality.
    Cell Metab 2017 Oct;26(4):585-587
    Energy Metabolism Laboratory, Institute of Translational Medicine, Swiss Federal Institute of Technology (ETH) Zurich, Zurich-Schwerzenbach 8603, Switzerland. Electronic address:
    The prospective cohort study, named PURE, found that in >135,000 participants from 18 countries, nutritive carbohydrates increase human mortality, whereas dietary fat reduces it, requesting a fundamental change of current nutritional guidelines. Experimental evidence from animal models provides synergizing mechanistic concepts as well as pharmacological options to mimic low-carb or ketogenic diets. Read More

    Fasting the Microbiota to Improve Metabolism?
    Cell Metab 2017 Oct;26(4):584-585
    European Genomic Institute for Diabetes (E.G.I.D), University of Lille, EGID, 59000 Lille, France; INSERM UMR 1011, 59000 Lille, France; Institut Pasteur de Lille, 59000 Lille, France; University Hospital CHU Lille, 59000 Lille, France. Electronic address:
    While intermittent or periodic fasting provides a variety of favorable health benefits, the molecular mediators of these effects are poorly understood. In this issue of Cell Metabolism, Li and colleagues (2017) highlight the role of gut microbiota in mediating benefits of intermittent fasting through activation of adipose tissue beiging. Read More

    Metabolic Disease Therapies.
    • Authors:
    Cell Metab 2017 Oct;26(4):579-583
    In anticipation of our upcoming Cell Symposium on Metabolic Disease Therapies in San Diego, CA, on October 15(th)-17(th) (http://cell-symposia.com/metabolic-therapies-2017/), the speakers and organizers share their perspectives on why now, more than ever, cutting-edge research is needed to support effective therapies to combat metabolic disease. Read More

    The Glia-Neuron Lactate Shuttle and Elevated ROS Promote Lipid Synthesis in Neurons and Lipid Droplet Accumulation in Glia via APOE/D.
    Cell Metab 2017 Nov 28;26(5):719-737.e6. Epub 2017 Sep 28.
    Department of Neuroscience, Baylor College of Medicine, Houston, TX 77030, USA; Jan and Dan Duncan Neurological Research Institute at Texas Children's Hospital, Houston, TX 77030, USA; Department of Molecular and Human Genetics, Baylor College of Medicine, Baylor College of Medicine, Houston, TX 77030, USA; Howard Hughes Medical Institute, Baylor College of Medicine, Houston, TX 77030, USA. Electronic address:
    Elevated reactive oxygen species (ROS) induce the formation of lipids in neurons that are transferred to glia, where they form lipid droplets (LDs). We show that glial and neuronal monocarboxylate transporters (MCTs), fatty acid transport proteins (FATPs), and apolipoproteins are critical for glial LD formation. MCTs enable glia to secrete and neurons to absorb lactate, which is converted to pyruvate and acetyl-CoA in neurons. Read More

    Molecular Integration of Incretin and Glucocorticoid Action Reverses Immunometabolic Dysfunction and Obesity.
    Cell Metab 2017 Oct 21;26(4):620-632.e6. Epub 2017 Sep 21.
    Institute for Diabetes and Obesity, Helmholtz Diabetes Center, Helmholtz Zentrum München, 85764 Neuherberg, Germany; Division of Metabolic Diseases, Department of Medicine, Technische Universität München, 80333 Munich, Germany; German Center for Diabetes Research (DZD), Helmholtz Zentrum München, Ingolstädter Landstraße, 85764 Neuherberg, Germany. Electronic address:
    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. Read More

    A Predictive Model for Selective Targeting of the Warburg Effect through GAPDH Inhibition with a Natural Product.
    Cell Metab 2017 Oct 14;26(4):648-659.e8. Epub 2017 Sep 14.
    Department of Pharmacology and Cancer Biology, Duke Cancer Institute, Duke University School of Medicine, Durham, NC 27710, USA. Electronic address:
    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. Read More

    Intermittent Fasting Promotes White Adipose Browning and Decreases Obesity by Shaping the Gut Microbiota.
    Cell Metab 2017 Oct 14;26(4):672-685.e4. Epub 2017 Sep 14.
    Laboratory of Metabolism, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA. Electronic address:
    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. Read More

    Dense Intra-adipose Sympathetic Arborizations Are Essential for Cold-Induced Beiging of Mouse White Adipose Tissue.
    Cell Metab 2017 Oct 14;26(4):686-692.e3. Epub 2017 Sep 14.
    Center for Life Sciences, Tsinghua University, Beijing 100084, China; Institute for Immunology and School of Medicine, Tsinghua University, Beijing 100084, China. Electronic address:
    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. Read More

    Pancreatic β Cell Regeneration as a Possible Therapy for Diabetes.
    Cell Metab 2017 Sep 5. Epub 2017 Sep 5.
    Joslin Diabetes Center, Harvard Medical School, Harvard Stem Cell Institute, Boston, MA 02215, USA. Electronic address:
    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). Read More

    Exploring Metabolic Configurations of Single Cells within Complex Tissue Microenvironments.
    Cell Metab 2017 Nov 7;26(5):788-800.e6. Epub 2017 Sep 7.
    Department of Laboratory Medicine, Medical University of Vienna, 1090 Vienna, Austria. Electronic address:
    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. Read More

    Persistence of Pancreatic Insulin mRNA Expression and Proinsulin Protein in Type 1 Diabetes Pancreata.
    Cell Metab 2017 Sep;26(3):568-575.e3
    Department of Pathology, Immunology, and Laboratory Medicine, The University of Florida Diabetes Institute, Gainesville, FL, USA. Electronic address:
    The canonical notion that type 1 diabetes (T1D) results following a complete destruction of β cells has recently been questioned as small amounts of C-peptide are detectable in patients with long-standing disease. We analyzed protein and gene expression levels for proinsulin, insulin, C-peptide, and islet amyloid polypeptide within pancreatic tissues from T1D, autoantibody positive (Ab+), and control organs. Insulin and C-peptide levels were low to undetectable in extracts from the T1D cohort; however, proinsulin and INS mRNA were detected in the majority of T1D pancreata. Read More

    Cell-Intrinsic Glycogen Metabolism Supports Early Glycolytic Reprogramming Required for Dendritic Cell Immune Responses.
    Cell Metab 2017 Sep;26(3):558-567.e5
    Cell, Molecular, and Biomedical Sciences Program, University of Vermont, Burlington, VT 05405, USA; Department of Medical Laboratory and Radiation Sciences, College of Nursing and Health Sciences, University of Vermont, Burlington, VT 05405, USA. Electronic address:
    Dendritic cell (DC) activation by Toll-like receptor (TLR) agonists causes rapid glycolytic reprogramming that is required to meet the metabolic demands of their immune activation. Recent efforts in the field have identified an important role for extracellular glucose sourcing to support DC activation. However, the contributions of intracellular glucose stores to these processes have not been well characterized. Read More

    Ketogenic Diet Reduces Midlife Mortality and Improves Memory in Aging Mice.
    Cell Metab 2017 Sep;26(3):547-557.e8
    Buck Institute for Research on Aging, Novato, CA 94945, USA; UCSF Division of Geriatrics, San Francisco, CA 94118, USA; Gladstone Institute of Virology and Immunology, San Francisco, CA 94158, USA. Electronic address:
    Ketogenic diets recapitulate certain metabolic aspects of dietary restriction such as reliance on fatty acid metabolism and production of ketone bodies. We investigated whether an isoprotein ketogenic diet (KD) might, like dietary restriction, affect longevity and healthspan in C57BL/6 male mice. We find that Cyclic KD, KD alternated weekly with the Control diet to prevent obesity, reduces midlife mortality but does not affect maximum lifespan. Read More

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