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    2309 results match your criteria Cell Metabolism [Journal]

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    A Predictive Model for Selective Targeting of the Warburg Effect through GAPDH Inhibition with a Natural Product.
    Cell Metab 2017 Sep 8. Epub 2017 Sep 8.
    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 Sep 13. Epub 2017 Sep 13.
    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 Sep 5. Epub 2017 Sep 5.
    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 Sep 5. Epub 2017 Sep 5.
    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

    A Ketogenic Diet Extends Longevity and Healthspan in Adult Mice.
    Cell Metab 2017 Sep;26(3):539-546.e5
    Department of Molecular Biosciences, School of Veterinary Medicine, University of California, Davis, Davis, CA, USA. Electronic address:
    Calorie restriction, without malnutrition, has been shown to increase lifespan and is associated with a shift away from glycolysis toward beta-oxidation. The objective of this study was to mimic this metabolic shift using low-carbohydrate diets and to determine the influence of these diets on longevity and healthspan in mice. C57BL/6 mice were assigned to a ketogenic, low-carbohydrate, or control diet at 12 months of age and were either allowed to live their natural lifespan or tested for physiological function after 1 or 14 months of dietary intervention. Read More

    Distinct Circadian Signatures in Liver and Gut Clocks Revealed by Ketogenic Diet.
    Cell Metab 2017 Sep;26(3):523-538.e5
    Center for Epigenetics and Metabolism, Department of Biological Chemistry, U1233 INSERM, University of California, Irvine, Irvine, CA, USA. Electronic address:
    The circadian clock orchestrates rhythms in physiology and behavior, allowing organismal adaptation to daily environmental changes. While food intake profoundly influences diurnal rhythms in the liver, how nutritional challenges are differentially interpreted by distinct tissue-specific clocks remains poorly explored. Ketogenic diet (KD) is considered to have metabolic and therapeutic value, though its impact on circadian homeostasis is virtually unknown. Read More

    Global Analysis of Plasma Lipids Identifies Liver-Derived Acylcarnitines as a Fuel Source for Brown Fat Thermogenesis.
    Cell Metab 2017 Sep;26(3):509-522.e6
    Department of Biochemistry, University of Utah School of Medicine, Salt Lake City, UT 84112, USA. Electronic address:
    Cold-induced thermogenesis is an energy-demanding process that protects endotherms against a reduction in ambient temperature. Using non-targeted liquid chromatography-mass spectrometry-based lipidomics, we identified elevated levels of plasma acylcarnitines in response to the cold. We found that the liver undergoes a metabolic switch to provide fuel for brown fat thermogenesis by producing acylcarnitines. Read More

    A Stat6/Pten Axis Links Regulatory T Cells with Adipose Tissue Function.
    Cell Metab 2017 Sep;26(3):475-492.e7
    Institute for Diabetes Research, Research Group Immune Tolerance in Diabetes, Helmholtz Diabetes Center at Helmholtz Zentrum München, 80939 Munich, Germany; German Center for Diabetes Research (DZD), 85764 Munich-Neuherberg, Germany. Electronic address:
    Obesity and type 2 diabetes are associated with metabolic defects and adipose tissue inflammation. Foxp3(+) regulatory T cells (Tregs) control tissue homeostasis by counteracting local inflammation. However, if and how T cells interlink environmental influences with adipocyte function remains unknown. Read More

    Disentangling High Fat, Low Carb, and Healthy Aging.
    Cell Metab 2017 Sep;26(3):458-459
    Department of Biomedical Sciences, University of North Dakota School of Medicine & Health Sciences, 504 Hamline Street, Grand Forks, ND 58203-9061, USA. Electronic address:
    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. Read More

    Meds Modify Microbiome, Mediating Their Effects.
    Cell Metab 2017 Sep;26(3):456-457
    University of Michigan Medical School, Ann Arbor, MI, USA. Electronic address:
    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. Read More

    The Liver as a Hub in Thermogenesis.
    Cell Metab 2017 Sep;26(3):454-455
    Medicine and Cell Biology and Physiology, Washington University School of Medicine, St. Louis, MO, USA. Electronic address:
    Manipulating thermogenesis could increase energy expenditure and improve metabolism. Brown fat is a major site of nonshivering thermogenesis, but other tissues, notably muscle and liver, can contribute to cold adaptation. In this issue, Simcox et al. Read More

    Women in Metabolism: The Next Generation.
    • Authors:
    Cell Metab 2017 Sep;26(3):449-453
    The "Rosies" of Cell Metabolism persist as a new generation enters the stage. With inspiration from this issue's cover art, we celebrate young and diverse scientists and the mentorship that has guided them throughout. Their stories come from different corners of the world but are tied together by a common thread of tenacity and perseverance. Read More

    Nonalcoholic Fatty Liver Disease as a Nexus of Metabolic and Hepatic Diseases.
    Cell Metab 2017 Aug 29. Epub 2017 Aug 29.
    Department of Medicine, Yale University School of Medicine, New Haven, CT 06510, USA; Department of Cellular and Molecular Physiology, Yale University School of Medicine, New Haven, CT 06510, USA; Howard Hughes Medical Institute, Yale University School of Medicine, New Haven, CT 06510, USA. Electronic address:
    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). Read More

    The Lymphatic Vasculature: Its Role in Adipose Metabolism and Obesity.
    Cell Metab 2017 Aug 22. Epub 2017 Aug 22.
    Center for Vascular and Developmental Biology, Feinberg Cardiovascular Research Institute, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA. Electronic address:
    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. Read More

    Genetic Depletion of Adipocyte Creatine Metabolism Inhibits Diet-Induced Thermogenesis and Drives Obesity.
    Cell Metab 2017 Aug 24. Epub 2017 Aug 24.
    Dana-Farber Cancer Institute, Boston, MA 02115, USA; Department of Cell Biology, Harvard University Medical School, Boston, MA 02115, USA. Electronic address:
    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). Read More

    The FGF21-CCL11 Axis Mediates Beiging of White Adipose Tissues by Coupling Sympathetic Nervous System to Type 2 Immunity.
    Cell Metab 2017 Sep 24;26(3):493-508.e4. Epub 2017 Aug 24.
    The State Key Laboratory of Pharmaceutical Biotechnology, The University of Hong Kong, 21 Sassoon Road, Laboratory Block, Pokfulam, Hong Kong, China; Department of Medicine, The University of Hong Kong, Hong Kong, China; Department of Pharmacology and Pharmacy, The University of Hong Kong, Hong Kong, China. Electronic address:
    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. Read More

    Creatine Fuels the Thermic Effect of Feeding.
    Cell Metab 2017 Aug 17. Epub 2017 Aug 17.
    Department of Medicine, University of California, San Diego, La Jolla, CA 92093, USA. Electronic address:
    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 of Cell Metabolism, Kazak et al. Read More

    Regulation of Stem Cell Aging by Metabolism and Epigenetics.
    Cell Metab 2017 Sep 17;26(3):460-474. Epub 2017 Aug 17.
    Gene Expression Laboratory, Salk Institute for Biological Studies, 10010 North Torrey Pines Road, La Jolla, CA 92037, USA. Electronic address:
    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. Read More

    Long-Term Cold Adaptation Does Not Require FGF21 or UCP1.
    Cell Metab 2017 Aug;26(2):437-446.e5
    Institute for Diabetes and Obesity, Helmholtz Diabetes Center, German Research Center for Environmental Health (GmbH), Neuherberg, Germany; German Center for Diabetes Research (DZD), Neuherberg, Germany; Department of Animal Physiology, Faculty of Biology, Philipps University of Marburg, Marburg, Germany. Electronic address:
    Brown adipose tissue (BAT)-dependent thermogenesis and its suggested augmenting hormone, FGF21, are potential therapeutic targets in current obesity and diabetes research. Here, we studied the role of UCP1 and FGF21 for metabolic homeostasis in the cold and dissected underlying molecular mechanisms using UCP1-FGF21 double-knockout mice. We report that neither UCP1 nor FGF21, nor even compensatory increases of FGF21 serum levels in UCP1 knockout mice, are required for defense of body temperature or for maintenance of energy metabolism and body weight. Read More

    Increased Total mtDNA Copy Number Cures Male Infertility Despite Unaltered mtDNA Mutation Load.
    Cell Metab 2017 Aug;26(2):429-436.e4
    Department of Mitochondrial Biology, Max Planck Institute for Biology of Ageing, 50931 Cologne, Germany; Department of Medical Biochemistry and Biophysics, Karolinska Institutet, 171 77 Stockholm, Sweden. Electronic address:
    Mutations of mtDNA cause mitochondrial diseases and are implicated in age-associated diseases and aging. Pathogenic mtDNA mutations are often present in a fraction of all mtDNA copies, and it has been widely debated whether the proportion of mutant genomes or the absolute number of wild-type molecules determines if oxidative phosphorylation (OXPHOS) will be impaired. Here, we have studied the male infertility phenotype of mtDNA mutator mice and demonstrate that decreasing mtDNA copy number worsens mitochondrial aberrations of spermatocytes and spermatids in testes, whereas an increase in mtDNA copy number rescues the fertility phenotype and normalizes testes morphology as well as spermatocyte proteome changes. Read More

    mTORC1 Regulates Mitochondrial Integrated Stress Response and Mitochondrial Myopathy Progression.
    Cell Metab 2017 Aug;26(2):419-428.e5
    Research Programs Unit, Molecular Neurology, University of Helsinki, 00290 Helsinki, Finland; Department of Neurology, Helsinki University Hospital, 00290 Helsinki, Finland; Neuroscience Center, University of Helsinki, 00790 Helsinki, Finland. Electronic address:
    Mitochondrial dysfunction elicits various stress responses in different model systems, but how these responses relate to each other and contribute to mitochondrial disease has remained unclear. Mitochondrial myopathy (MM) is the most common manifestation of adult-onset mitochondrial disease and shows a multifaceted tissue-specific stress response: (1) transcriptional response, including metabolic cytokines FGF21 and GDF15; (2) remodeling of one-carbon metabolism; and (3) mitochondrial unfolded protein response. We show that these processes are part of one integrated mitochondrial stress response (ISRmt), which is controlled by mTORC1 in muscle. Read More

    Triglyceride Synthesis by DGAT1 Protects Adipocytes from Lipid-Induced ER Stress during Lipolysis.
    Cell Metab 2017 Aug;26(2):407-418.e3
    Department of Genetics and Complex Diseases, Harvard T.H. Chan School of Public Health, Boston, MA 02115, USA; Department of Cell Biology, Harvard Medical School, Boston, MA 02115, USA; Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA. Electronic address:
    Triglyceride (TG) storage in adipose tissue provides the major reservoir for metabolic energy in mammals. During lipolysis, fatty acids (FAs) are hydrolyzed from adipocyte TG stores and transported to other tissues for fuel. For unclear reasons, a large portion of hydrolyzed FAs in adipocytes is re-esterified to TGs in a "futile," ATP-consuming, energy dissipating cycle. Read More

    Acetyl CoA Carboxylase Inhibition Reduces Hepatic Steatosis but Elevates Plasma Triglycerides in Mice and Humans: A Bedside to Bench Investigation.
    Cell Metab 2017 Aug;26(2):394-406.e6
    Departments of Internal Medicine and Molecular Genetics, University of Texas Southwestern Medical Center, Dallas, TX 75390-9046, USA. Electronic address:
    Inhibiting lipogenesis prevents hepatic steatosis in rodents with insulin resistance. To determine if reducing lipogenesis functions similarly in humans, we developed MK-4074, a liver-specific inhibitor of acetyl-CoA carboxylase (ACC1) and (ACC2), enzymes that produce malonyl-CoA for fatty acid synthesis. MK-4074 administered to subjects with hepatic steatosis for 1 month lowered lipogenesis, increased ketones, and reduced liver triglycerides by 36%. Read More

    A Hypothalamic Phosphatase Switch Coordinates Energy Expenditure with Feeding.
    Cell Metab 2017 Aug;26(2):375-393.e7
    Metabolic Disease and Obesity Program, Biomedicine Discovery Institute, Monash University, Victoria 3800, Australia; Department of Biochemistry and Molecular Biology, Monash University, Victoria 3800, Australia. Electronic address:
    Beige adipocytes can interconvert between white and brown-like states and switch between energy storage versus expenditure. Here we report that beige adipocyte plasticity is important for feeding-associated changes in energy expenditure and is coordinated by the hypothalamus and the phosphatase TCPTP. A fasting-induced and glucocorticoid-mediated induction of TCPTP, inhibited insulin signaling in AgRP/NPY neurons, repressed the browning of white fat and decreased energy expenditure. Read More

    Neuronal Stimulation Triggers Neuronal Glycolysis and Not Lactate Uptake.
    Cell Metab 2017 Aug;26(2):361-374.e4
    Department of Neurobiology, Harvard Medical School, 200 Longwood Avenue, Boston, MA 02115, USA. Electronic address:
    Proper brain function requires a substantial energy supply, up to 20% of whole-body energy in humans, and brain activation produces large dynamic variations in energy demand. While local increases in cerebral blood flow are well known, the cellular responses to energy demand are controversial. During brain excitation, glycolysis of glucose to lactate temporarily exceeds the rate of mitochondrial fuel oxidation; although the increased energy demand occurs mainly within neurons, some have suggested this glycolysis occurs mainly in astrocytes, which then shuttle lactate to neurons as their primary fuel. Read More

    Loss of Brain Aerobic Glycolysis in Normal Human Aging.
    Cell Metab 2017 Aug;26(2):353-360.e3
    Mallinckrodt Institute of Radiology, Washington University School of Medicine, St. Louis, MO 63110, USA; Knight Alzheimer's Disease Research Center, Washington University School of Medicine, St. Louis, MO 63110, USA.
    The normal aging human brain experiences global decreases in metabolism, but whether this affects the topography of brain metabolism is unknown. Here we describe PET-based measurements of brain glucose uptake, oxygen utilization, and blood flow in cognitively normal adults from 20 to 82 years of age. Age-related decreases in brain glucose uptake exceed that of oxygen use, resulting in loss of brain aerobic glycolysis (AG). Read More

    The Sustained Effects of a Dual GIP/GLP-1 Receptor Agonist, NNC0090-2746, in Patients with Type 2 Diabetes.
    Cell Metab 2017 Aug;26(2):343-352.e2
    Novo Nordisk Research Center Indianapolis, Indianapolis, IN 46241, USA. Electronic address:
    Unimolecular dual incretins derived from hybridized glucagon-like peptide 1 (GLP-1) and glucose-dependent insulinotropic peptide (GIP) sequences have demonstrated synergistic reduction of adiposity in animal models and reductions of hyperglycemia in short-duration human trials. Here, we extend the characterization of NNC0090-2746 (also known as RG7697), a fatty-acylated dual agonist possessing in vitro balanced GIPR and GLP-1R agonism. In this 12-week, randomized, placebo-controlled, double-blind phase 2a trial, patients with type 2 diabetes inadequately controlled with metformin received 1. Read More

    Sweet Sixteenth for ChREBP: Established Roles and Future Goals.
    Cell Metab 2017 Aug;26(2):324-341
    Inserm, U1016, Institut Cochin, 75014 Paris, France; CNRS UMR 8104, 75014 Paris, France; Université Paris Descartes, Sorbonne Paris Cité, 75006 Paris, France. Electronic address:
    With the identification of ChREBP in 2001, our interest in understanding the molecular control of carbohydrate sensing has surged. While ChREBP was initially studied as a master regulator of lipogenesis in liver and fat tissue, it is now clear that ChREBP functions as a central metabolic coordinator in a variety of cell types in response to environmental and hormonal signals, with wide implications in health and disease. Celebrating its sweet sixteenth birthday, we review here the current knowledge about the function and regulation of ChREBP throughout usual and less explored tissues, to recapitulate ChREBP's role as a whole-body glucose sensor. Read More

    The Dawn of the Age of Amino Acid Sensors for the mTORC1 Pathway.
    Cell Metab 2017 Aug;26(2):301-309
    Whitehead Institute for Biomedical Research, 455 Main Street, Cambridge, MA 02142, USA; Department of Biology, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, MA 02139, USA; Howard Hughes Medical Institute, Department of Biology, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, MA 02139, USA; Koch Institute for Integrative Cancer Research at MIT, 77 Massachusetts Avenue, Cambridge, MA 02139, USA; Broad Institute, 415 Main Street, Cambridge, MA 02142, USA. Electronic address:
    The mechanistic target of rapamycin complex 1 (mTORC1) is a master regulator of cell growth that responds to a diverse set of environmental inputs, including amino acids. Over the past 10 years, a number of proteins have been identified that help transmit amino acid availability to mTORC1. However, amino acid sensors for this pathway have only recently been discovered. Read More

    Causes, Characteristics, and Consequences of Metabolically Unhealthy Normal Weight in Humans.
    Cell Metab 2017 Aug;26(2):292-300
    Department of Internal Medicine IV, University Hospital Tübingen, Tübingen, Germany; Institute of Diabetes Research and Metabolic Diseases (IDM) of the Helmholtz Center Munich at the University of Tübingen, Tübingen, Germany; German Center for Diabetes Research (DZD), Tübingen, Germany. Electronic address:
    A BMI in the normal range associates with a decreased risk of cardiometabolic disease and all-cause mortality. However, not all subjects in this BMI range have this low risk. Compared to people who are of normal weight and metabolically healthy, subjects who are of normal weight but metabolically unhealthy (∼20% of the normal weight adult population) have a greater than 3-fold higher risk of all-cause mortality and/or cardiovascular events. Read More

    Once Blind, Now We See GLP-1 Molecular Action.
    Cell Metab 2017 Aug;26(2):289-291
    Department of Chemistry, Indiana University, Bloomington, IN 47405, USA. Electronic address:
    The macromolecular mechanics of GLP-1 with its cell surface receptor came into focus as two landmark publications recently published in Nature collectively herald advancement in structure-based design for a receptor class of great therapeutic importance (Jazayeri et al., 2017; Zhang et al., 2017). Read More

    What's So Special about FGF19-Unique Effects Reported on Skeletal Muscle Mass and Function.
    Cell Metab 2017 Aug;26(2):287-288
    Novartis Institutes for Biomedical Research, 181 Massachusetts Avenue, Cambridge, MA 02139, USA. Electronic address:
    In a recent study published in Nature 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. Read More

    Burning Fat and Building Bone by FSH Blockade.
    Cell Metab 2017 Aug;26(2):285-287
    Diabetes Center and Department of Cell and Tissue Biology, University of California, San Francisco, San Francisco, CA, USA. Electronic address:
    The rise of follicle-stimulating hormone (FSH) is a hallmark of menopause associated with osteoporosis and visceral adiposity. In Nature, Zaidi and colleagues (Liu et al., 2017) report that blocking FSH action reduces body fat by promoting brown/beige fat thermogenesis, potentially providing a new intervention for the treatment of menopause-related metabolic diseases. Read More

    Holding Onto Youth.
    Cell Metab 2017 Aug;26(2):284-285
    Montreal Neurological Institute, McGill University, Montreal, QC H3A 2B4, Canada.
    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 of Cell Metabolism, Goyal et al. (2017) demonstrate that AG declines with age in the human brain, disappearing almost completely by age 60. Read More

    Plasma Mannose Levels Are Associated with Incident Type 2 Diabetes and Cardiovascular Disease.
    Cell Metab 2017 Aug;26(2):281-283
    Department of Molecular and Clinical Medicine, University of Gothenburg and Sahlgrenska University Hospital, Gothenburg 41345, Sweden. Electronic address:
    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. Read More

    Chronic Sucralose or L-Glucose Ingestion Does Not Suppress Food Intake.
    Cell Metab 2017 Aug;26(2):279-280
    Charles Perkins Centre and School of Life and Environmental Sciences, University of Sydney, Camperdown, NSW 2006, Australia; Dr. John and Anne Chong Lab for Functional Genomics, University of Sydney, Camperdown, NSW 2006, Australia. Electronic address:
    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. Read More

    Insulin Regulation of Proteostasis and Clinical Implications.
    Cell Metab 2017 Aug 14;26(2):310-323. Epub 2017 Jul 14.
    Division of Endocrinology, Diabetes, Metabolism, and Nutrition, Mayo Clinic, 200 First Street SW, Rochester, MN 55905, USA. Electronic address:
    Maintenance and modification of the cellular proteome are at the core of normal cellular physiology. Although insulin is well known for its control of glucose homeostasis, its critical role in maintaining proteome homeostasis (proteostasis) is less appreciated. Insulin signaling regulates protein synthesis and degradation as well as posttranslational modifications at the tissue level and coordinates proteostasis at the organism level. Read More

    Metabolic Regulation of T Cell Longevity and Function in Tumor Immunotherapy.
    Cell Metab 2017 Jul;26(1):94-109
    Center for Cell-Based Therapy, National Cancer Institute (NCI), National Institutes of Health (NIH), Bethesda, MD 20892, USA; Surgery Branch, National Cancer Institute (NCI), National Institutes of Health (NIH), Bethesda, MD 20892, USA. Electronic address:
    Cancer immunotherapy is an increasingly successful strategy for the treatment of patients who have advanced or conventional therapy-resistant cancers. T cells are key mediators of tumor destruction and their specificity for tumor-expressed antigens is of paramount importance, but other T cell-intrinsic qualities, such as durability, longevity, and functionality also play important roles in determining the efficacy of immunotherapy. The cellular energetic pathways that are utilized by T cells play a key role in regulating each of these qualities. Read More

    Fighting Fire with Fiber: Preventing T Cell Infiltration in Diabetes.
    Cell Metab 2017 Jul;26(1):8-10
    Departments of Immunology and Infectious Diseases and Genetics and Complex Diseases, Harvard T.H. Chan School of Public Health, Boston, MA 02115, USA; Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA; Department and Division of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA 02215, USA. Electronic address:
    Diet can alter the gut microbiota and shift its production of metabolites, which affect systemic immune function. In Nature Immunology, Mariño et al. (2017) explore diet-gut microbiome interactions in type 1 diabetes and identify mechanisms by which short-chain fatty acids prevent T cell destruction of pancreatic β-cells. Read More

    Inflammasomes on the Crossroads of Innate Immune Recognition and Metabolic Control.
    Cell Metab 2017 Jul;26(1):71-93
    Institute of Innate Immunity, University Hospitals Bonn, 53127 Bonn, Germany; Division of Infectious Diseases and Immunology, Department of Medicine, University of Massachusetts Medical School, Worcester, MA 01655, USA; German Center of Neurodegenerative Diseases (DZNE), 53127 Bonn, Germany; Centre for Molecular Inflammation Research (CEMIR), Norwegian University of Science and Technology, 7491 Trondheim, Norway. Electronic address:
    Inflammasomes are protein complexes formed upon encounter of microbial or damage-associated stimuli. The main output of inflammasome assembly is activation of caspase-1, a protease involved in both pro-inflammatory and host-protective responses. Defined bacterial or viral ligands have been identified for the inflammasome-forming receptors AIM2, NLRP1, and NLRC4. Read More

    Will Gut Microbiota Help Design the Next Generation of GLP-1-Based Therapies for Type 2 Diabetes?
    Cell Metab 2017 Jul;26(1):6-7
    Department of Food and Nutritional Sciences, University of Reading, Whiteknights Campus, PO Box 226, Reading RG6 6AP, UK. Electronic address:
    Glucagon-like peptide one (GLP-1)-based therapies for reducing hyperglycemia in type 2 diabetic patients are efficient, though some individuals develop GLP-1 resistance. In a recent issue of Cell Metabolism, Grasset et al. (2017) demonstrated that GLP-1 sensitivity is modulated by gut bacteria through NO signaling in the enteric nervous system. Read More

    Similarities and Distinctions of Cancer and Immune Metabolism in Inflammation and Tumors.
    Cell Metab 2017 Jul;26(1):49-70
    Vanderbilt Center for Immunobiology, Department of Pathology, Microbiology, and Immunology, Vanderbilt University Medical Center and Department of Cancer Biology, Vanderbilt University, Nashville, TN 37232, USA. Electronic address:
    It has been appreciated for nearly 100 years that cancer cells are metabolically distinct from resting tissues. More recently understood is that this metabolic phenotype is not unique to cancer cells but instead reflects characteristics of proliferating cells. Similar metabolic transitions also occur in the immune system as cells transition from resting state to stimulated effectors. Read More

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