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    2392 results match your criteria Cell Metabolism [Journal]

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    An Integrated Understanding of the Rapid Metabolic Benefits of a Carbohydrate-Restricted Diet on Hepatic Steatosis in Humans.
    Cell Metab 2018 Feb 7. Epub 2018 Feb 7.
    Department of Molecular and Clinical Medicine, University of Gothenburg, and Sahlgrenska University Hospital, Gothenburg, Sweden. Electronic address:
    A carbohydrate-restricted diet is a widely recommended intervention for non-alcoholic fatty liver disease (NAFLD), but a systematic perspective on the multiple benefits of this diet is lacking. Here, we performed a short-term intervention with an isocaloric low-carbohydrate diet with increased protein content in obese subjects with NAFLD and characterized the resulting alterations in metabolism and the gut microbiota using a multi-omics approach. We observed rapid and dramatic reductions of liver fat and other cardiometabolic risk factors paralleled by (1) marked decreases in hepatic de novo lipogenesis; (2) large increases in serum β-hydroxybutyrate concentrations, reflecting increased mitochondrial β-oxidation; and (3) rapid increases in folate-producing Streptococcus and serum folate concentrations. Read More

    Glucose-Dependent Granule Docking Limits Insulin Secretion and Is Decreased in Human Type 2 Diabetes.
    Cell Metab 2018 Feb;27(2):470-478.e4
    Department of Medical Cell Biology, Uppsala University, BMC 571, 75123 Uppsala, Sweden. Electronic address:
    Glucose-stimulated insulin secretion is biphasic, with a rapid first phase and a slowly developing sustained second phase; both are disturbed in type 2 diabetes (T2D). Biphasic secretion results from vastly different release probabilities of individual insulin granules, but the morphological and molecular basis for this is unclear. Here, we show that human insulin secretion and exocytosis critically depend on the availability of membrane-docked granules and that T2D is associated with a strong reduction in granule docking. Read More

    Palmitic Acid Hydroxystearic Acids Activate GPR40, Which Is Involved in Their Beneficial Effects on Glucose Homeostasis.
    Cell Metab 2018 Feb;27(2):419-427.e4
    Division of Endocrinology, Diabetes, and Metabolism, Department of Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, Center for Life Sciences, Room 747, 330 Brookline Avenue, Boston, MA 02215, USA. Electronic address:
    Palmitic acid hydroxystearic acids (PAHSAs) are endogenous lipids with anti-diabetic and anti-inflammatory effects. PAHSA levels are reduced in serum and adipose tissue of insulin-resistant people and high-fat diet (HFD)-fed mice. Here, we investigated whether chronic PAHSA treatment enhances insulin sensitivity and which receptors mediate PAHSA effects. Read More

    Kynurenic Acid and Gpr35 Regulate Adipose Tissue Energy Homeostasis and Inflammation.
    Cell Metab 2018 Feb;27(2):378-392.e5
    Department of Physiology and Pharmacology, Molecular and Cellular Exercise Physiology, Karolinska Institutet, 17177 Stockholm, Sweden. Electronic address:
    The role of tryptophan-kynurenine metabolism in psychiatric disease is well established, but remains less explored in peripheral tissues. Exercise training activates kynurenine biotransformation in skeletal muscle, which protects from neuroinflammation and leads to peripheral kynurenic acid accumulation. Here we show that kynurenic acid increases energy utilization by activating G protein-coupled receptor Gpr35, which stimulates lipid metabolism, thermogenic, and anti-inflammatory gene expression in adipose tissue. Read More

    The Small Intestine Converts Dietary Fructose into Glucose and Organic Acids.
    Cell Metab 2018 Feb;27(2):351-361.e3
    Department of Chemistry and Lewis-Sigler Institute for Integrative Genomics, Princeton University, Princeton, NJ 08544, USA. Electronic address:
    Excessive consumption of sweets is a risk factor for metabolic syndrome. A major chemical feature of sweets is fructose. Despite strong ties between fructose and disease, the metabolic fate of fructose in mammals remains incompletely understood. Read More

    Digoxin Suppresses Pyruvate Kinase M2-Promoted HIF-1α Transactivation in Steatohepatitis.
    Cell Metab 2018 Feb;27(2):339-350.e3
    Section of Digestive Diseases, Yale University, New Haven, CT 06520, USA; West Haven Veterans Medical Center, West Haven, CT 06516, USA. Electronic address:
    Sterile inflammation after tissue damage is a ubiquitous response, yet it has the highest amplitude in the liver. This has major clinical consequences, for alcoholic and non-alcoholic steatohepatitis (ASH and NASH) account for the majority of liver disease in industrialized countries and both lack therapy. Requirements for sustained sterile inflammation include increased oxidative stress and activation of the HIF-1α signaling pathway. Read More

    Metabolism in Pluripotent Stem Cells and Early Mammalian Development.
    Cell Metab 2018 Feb;27(2):332-338
    Department of Pathology and Laboratory Medicine, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA; California NanoSystems Institute, University of California, Los Angeles, Los Angeles, CA 90095, USA; Department of Bioengineering, University of California, Los Angeles, Los Angeles, CA 90095, USA; Molecular Biology Institute, University of California, Los Angeles, Los Angeles, CA 90095, USA; Jonsson Comprehensive Cancer Center, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA; Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research, University of California, Los Angeles, Los Angeles, CA 90095, USA. Electronic address:
    Emerging and seminal studies have shown that cell metabolism influences gene expression by modifying the epigenome, which can regulate stem cell pluripotency, differentiation, and somatic cell reprogramming. Core pluripotency factors and developmental regulators reciprocally control the expression of key metabolism genes and their encoded pathways. Recent technological advances enabling sensitive detection methods during early mammalian development revealed the state-specific and context-dependent coordination of signal transduction, histone modifications, and gene expression in developing, resting, and malnourished embryos. Read More

    The HETE Is on FFAR1 and Pancreatic Islet Cells.
    Cell Metab 2018 Feb;27(2):273-275
    Center for Basic Metabolic Research, University of Copenhagen, Denmark; Laboratory for Molecular Pharmacology, Department for Biomedical Research, Faculty of Health Sciences, University of Copenhagen, Denmark. Electronic address:
    It is known but generally unappreciated that the fatty acid receptor FFAR1 (GPR40) is responsible for a major part of glucose-induced insulin secretion. This puzzling fact is now explained by Tunaru et al. (2018), who demonstrate that glucose-induced 20-hydroxyeicosatetraenoic acid (20-HETE) amplifies insulin secretion through autocrine activation of FFAR1. Read More

    Metabolite-Induced Protein Expression Guided by Metabolomics and Systems Biology.
    Cell Metab 2018 Feb;27(2):270-272
    The Scripps Research Institute, Scripps Center for Metabolomics and Mass Spectrometry, La Jolla, CA, USA. Electronic address:
    Metabolomics combined with systems biology can be used to identify endogenous metabolites that modulate protein expression. Recent examples include the 2-fold enhancements of pertussis toxin protein in vaccine production and myelin basic protein expression in oligodendrocyte maturation; both applied a metabolomics-systems strategy to identify active metabolites. Read More

    Mealtime Is NONO Speckled: Timing Hepatic Adaptation to Food.
    Cell Metab 2018 Feb;27(2):268-270
    Charité Universitätsmedizin Berlin, Laboratory of Chronobiology, 10117 Berlin, Germany. Electronic address:
    You are what you eat; but when you eat also seems to be important for a healthy metabolism. In this issue of Cell Metabolism, Benegiamo et al. (2018) uncover a mechanism by which the RNA-binding protein NONO promotes the time-of-day-dependent expression of key metabolic genes at a post-transcriptional level in response to nutrition. Read More

    Cultivating a Relationship with Gut Bacteria.
    Cell Metab 2018 Feb;27(2):267-268
    California Institute of Technology, Pasadena, CA, USA.
    While the gut microbiome largely benefits host physiology, the impact of symbiosis on bacterial fitness has not been rigorously investigated. In this issue, Storelli et al. (2018) provide evidence that Drosophila actively cultivate a relationship with the growth-promoting bacterium Lactobacillus plantarum, delivering mutual benefits under nutrient-poor conditions. Read More

    The RNA-Binding Protein NONO Coordinates Hepatic Adaptation to Feeding.
    Cell Metab 2018 Feb 18;27(2):404-418.e7. Epub 2018 Jan 18.
    Regulatory Biology Laboratory, Salk Institute for Biological Studies, La Jolla, CA 92037, USA. Electronic address:
    The mechanisms by which feeding and fasting drive rhythmic gene expression for physiological adaptation to daily rhythm in nutrient availability are not well understood. Here we show that, upon feeding, the RNA-binding protein NONO accumulates within speckle-like structures in liver cell nuclei. Combining RNA-immunoprecipitation and sequencing (RIP-seq), we find that an increased number of RNAs are bound by NONO after feeding. Read More

    Let-7 Suppresses B Cell Activation through Restricting the Availability of Necessary Nutrients.
    Cell Metab 2018 Feb 11;27(2):393-403.e4. Epub 2018 Jan 11.
    Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA 91125, USA. Electronic address:
    The control of uptake and utilization of necessary extracellular nutrients-glucose and glutamine-is an important aspect of B cell activation. Let-7 is a family of microRNAs known to be involved in metabolic control. Here, we employed several engineered mouse models, including B cell-specific overexpression of Lin28a or the let-7a-1/let-7d/let-7f-1 cluster (let-7adf) and knockout of individual let-7 clusters to show that let-7adf specifically inhibits T cell-independent (TI) antigen-induced immunoglobulin (Ig)M antibody production. Read More

    Basal Mitophagy Occurs Independently of PINK1 in Mouse Tissues of High Metabolic Demand.
    Cell Metab 2018 Feb 11;27(2):439-449.e5. Epub 2018 Jan 11.
    MRC Protein Phosphorylation and Ubiquitylation Unit, University of Dundee, Dundee DD1 5EH, UK. Electronic address:
    Dysregulated mitophagy has been linked to Parkinson's disease (PD) due to the role of PTEN-induced kinase 1 (PINK1) in mediating depolarization-induced mitophagy in vitro. Elegant mouse reporters have revealed the pervasive nature of basal mitophagy in vivo, yet the role of PINK1 and tissue metabolic context remains unknown. Using mito-QC, we investigated the contribution of PINK1 to mitophagy in metabolically active tissues. Read More

    As Extracellular Glutamine Levels Decline, Asparagine Becomes an Essential Amino Acid.
    Cell Metab 2018 Feb 11;27(2):428-438.e5. Epub 2018 Jan 11.
    Department of Cancer Biology and Genetics, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA; Herman B. Wells Center for Pediatric Research, Indiana University School of Medicine, Indianapolis, IN 46202, USA. Electronic address:
    When mammalian cells are deprived of glutamine, exogenous asparagine rescues cell survival and growth. Here we report that this rescue results from use of asparagine in protein synthesis. All mammalian cell lines tested lacked cytosolic asparaginase activity and could not utilize asparagine to produce other amino acids or biosynthetic intermediates. Read More

    SERCA2b Cycles Its Way to UCP1-Independent Thermogenesis in Beige Fat.
    Cell Metab 2018 Jan;27(1):7-9
    Center for Integrative Metabolic and Endocrine Research, Wayne State University School of Medicine, Detroit, MI 48202, USA. Electronic address:
    A new study in Nature Medicine, by Ikeda et al. (2017), reports that calcium cycling in beige adipocytes elevates energy expenditure and glucose oxidation in the absence of uncoupling protein 1. Thermogenic calcium cycling in beige fat is mediated by SERCA2b and improves cold tolerance and metabolic status. Read More

    Anatomical, Physiological, and Functional Diversity of Adipose Tissue.
    Cell Metab 2018 Jan;27(1):68-83
    Department of Developmental and Cell Biology, University of California, Irvine, 845 Health Sciences Road, Irvine, CA 92697, USA; Sue and Bill Gross Stem Cell Research Center, University of California, Irvine, Irvine, CA 92697, USA; Center for Complex Biological Systems, University of California, Irvine, Irvine, CA 92697, USA. Electronic address:
    Adipose tissue depots can exist in close association with other organs, where they assume diverse, often non-traditional functions. In stem cell-rich skin, bone marrow, and mammary glands, adipocytes signal to and modulate organ regeneration and remodeling. Skin adipocytes and their progenitors signal to hair follicles, promoting epithelial stem cell quiescence and activation, respectively. Read More

    Apoptotic Regulatory T Cells Retain Suppressive Function through Adenosine.
    Cell Metab 2018 Jan;27(1):5-7
    Division of Nephrology and Department of Pediatrics, Children's Hospital of Philadelphia and University of Pennsylvania, Philadelphia, PA 19104, USA. Electronic address:
    Regulatory T cells maintain tolerance and prevent autoimmunity, but their suppressive effects can hinder immune responses against cancer. In Nature Immunology, Maj et al., 2017 report that regulatory T cells can execute these actions through the nucleoside adenosine even after cell death. Read More

    Metabolic Reprogramming via Targeting CD38 NADase Augments Adoptive T Cell Therapy.
    Cell Metab 2018 Jan;27(1):3-5
    Department of Tumor Biology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL 33612, USA. Electronic address:
    One strategy to improve the potency of adoptive T cell therapy is to augment the function and persistence of anti-tumor T cells. In this issue of Cell Metabolism, Chatterjee et al. (2018) demonstrate that intratumoral CD4T cell functions and memory can be improved by targeting a CD38-NAD-Sirt1-Foxo1 metabolic circuit. Read More

    SnapShot: Niche Determines Adipocyte Character II.
    Cell Metab 2018 Jan;27(1):266-266.e1
    Department of Molecular and Integrative Physiology, University of Michigan Medical School, Ann Arbor, MI, USA.
    The intrinsic cellular and metabolic properties of an adipocyte are shaped by the specific niche in which it resides. The diverse and discrete locations of major and minor rodent adipose depots are depicted in Part I. In Part II, the molecular and functional characteristics of four major types of adipocytes are described. Read More

    SnapShot: Niche Determines Adipocyte Character I.
    Cell Metab 2018 Jan;27(1):264-264.e1
    Department of Molecular and Integrative Physiology, University of Michigan Medical School, Ann Arbor, MI, USA.
    Adipose tissues are complex organs, with central roles in energy homeostasis as well as local functions. Adipocytes develop in diverse, discrete locations throughout the body. Important regional differences in adipocytes exist, and diseases that affect adipose tissues often demonstrate depot-specific effects. Read More

    An Adipose Tissue Atlas: An Image-Guided Identification of Human-like BAT and Beige Depots in Rodents.
    Cell Metab 2018 Jan;27(1):252-262.e3
    Department of Radiology, University of Texas Southwestern Medical Center, Dallas, TX 75390-8542, USA. Electronic address:
    [F]Fluorodeoxyglucose-PET/CT (F-FDG-PET/CT) imaging has been invaluable for visualizing metabolically active adipose tissues in humans with potential anti-diabetic and anti-obesity effects. To explore whether mice display human-like fat depots in anatomically comparable regions, we mapped fat depots using glucose or fatty acid imaging tracers, such asF-FDG through PET/CT or [I]-β-methyl-p-iodophenyl-pentadecanoic acid with SPECT/CT imaging, to analogous depots in mice. Using this type of image analysis with both probes, we define a large number of additional areas of high metabolic activity corresponding to novel fat pads. Read More

    Extracellular Vesicles Provide a Means for Tissue Crosstalk during Exercise.
    Cell Metab 2018 Jan;27(1):237-251.e4
    Cellular and Molecular Metabolism, Garvan Institute of Medical Research, Sydney, NSW, Australia; St Vincent's Clinical School, University of New South Wales, Sydney, NSW, Australia. Electronic address:
    Exercise stimulates the release of molecules into the circulation, supporting the concept that inter-tissue signaling proteins are important mediators of adaptations to exercise. Recognizing that many circulating proteins are packaged in extracellular vesicles (EVs), we employed quantitative proteomic techniques to characterize the exercise-induced secretion of EV-contained proteins. Following a 1-hr bout of cycling exercise in healthy humans, we observed an increase in the circulation of over 300 proteins, with a notable enrichment of several classes of proteins that compose exosomes and small vesicles. Read More

    Three-Dimensional Adipose Tissue Imaging Reveals Regional Variation in Beige Fat Biogenesis and PRDM16-Dependent Sympathetic Neurite Density.
    Cell Metab 2018 Jan;27(1):226-236.e3
    Laboratory of Molecular Metabolism, The Rockefeller University, New York, NY, USA. Electronic address:
    While the cell-intrinsic pathways governing beige adipocyte development and phenotype have been increasingly delineated, comparatively little is known about how beige adipocytes interact with other cell types in fat. Here, we introduce a whole-tissue clearing method for adipose that permits immunolabeling and three-dimensional profiling of structures including thermogenic adipocytes and sympathetic innervation. We found that tissue architecture and sympathetic innervation differ significantly between subcutaneous and visceral depots. Read More

    Repression of Adipose Tissue Fibrosis through a PRDM16-GTF2IRD1 Complex Improves Systemic Glucose Homeostasis.
    Cell Metab 2018 Jan;27(1):180-194.e6
    UCSF Diabetes Center, San Francisco, CA, USA; Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research, San Francisco, CA, USA; Department of Cell and Tissue Biology, University of California, San Francisco, San Francisco, CA, USA. Electronic address:
    Adipose tissue fibrosis is a hallmark of malfunction that is linked to insulin resistance and type 2 diabetes; however, what regulates this process remains unclear. Here we show that the PRDM16 transcriptional complex, a dominant activator of brown/beige adipocyte development, potently represses adipose tissue fibrosis in an uncoupling protein 1 (UCP1)-independent manner. By purifying the PRDM16 complex, we identified GTF2IRD1, a member of the TFII-I family of DNA-binding proteins, as a cold-inducible transcription factor that mediates the repressive action of the PRDM16 complex on fibrosis. Read More

    Aminoacylation of Proteins: New Targets for the Old ARSenal.
    Cell Metab 2018 Jan;27(1):1-3
    Goodman Cancer Research Center, McGill University, Montreal, QC H3A 1A3, Canada; Department of Biochemistry, McGill University, Montreal, QC H3A 1A3, Canada. Electronic address:
    Besides charging tRNAs with their cognate amino acids, aminoacyl-tRNA synthetases (ARSs) are involved in a plethora of non-canonical functions, including development, immune response, and angiogenesis. In this issue of Cell Metabolism, He et al. (2018) report a novel biochemical function of ARSs: posttranslational addition of amino acids to lysine residues in proteins. Read More

    Could Ceramides Become the New Cholesterol?
    Cell Metab 2018 Feb 4;27(2):276-280. Epub 2018 Jan 4.
    Department of Nutrition and Integrative Physiology, University of Utah, Salt Lake City, UT 84112, USA. Electronic address:
    The Mayo Clinic recently introduced a diagnostic test that quantifies plasma ceramides in order to identify patients at risk of major adverse cardiac events. By comparing recent discoveries about these biomarker ceramides with the exhaustive body of literature surrounding cholesterol, Summers aims to highlight important advances and critically needed areas of investigation on this exciting class of bioactive lipids. Read More

    Drosophila Perpetuates Nutritional Mutualism by Promoting the Fitness of Its Intestinal Symbiont Lactobacillus plantarum.
    Cell Metab 2018 Feb 28;27(2):362-377.e8. Epub 2017 Dec 28.
    Institut de Génomique Fonctionnelle de Lyon (IGFL), Université de Lyon, Ecole Normale Supérieure de Lyon, CNRS UMR 5242, Université Claude Bernard Lyon 1, 69364 Lyon Cedex 07, France. Electronic address:
    Facultative animal-bacteria symbioses, which are critical determinants of animal fitness, are largely assumed to be mutualistic. However, whether commensal bacteria benefit from the association has not been rigorously assessed. Using a simple and tractable gnotobiotic model- Drosophila mono-associated with one of its dominant commensals, Lactobacillus plantarum-we reveal that in addition to benefiting animal growth, this facultative symbiosis has a positive impact on commensal bacteria fitness. Read More

    mTORC1 Signaling: A Double-Edged Sword in Diabetic β Cells.
    Cell Metab 2018 Feb 21;27(2):314-331. Epub 2017 Dec 21.
    University of Bremen, Centre for Biomolecular Interactions Bremen, Bremen 28359, Germany. Electronic address:
    The mechanistic target of rapamycin complex 1 (mTORC1) is a central regulator of metabolic and nutrient cues that integrates environmental inputs into downstream signaling pathways to control cellular metabolism, growth, and survival. While numerous in vitro and in vivo studies reported the positive functions of mTORC1 in the regulation of β cell survival and proliferation under physiological conditions, more recent work demonstrates the opposite in the long term; this is exemplified by the constitutive inappropriate hyper-activation of mTORC1 in diabetic islets or β cells under conditions of increased β cell stress and metabolic demands. These recent findings uncover mTORC1's importance as an emerging significant player in the development and progression of β cell failure in type 2 diabetes and suggest that mTORC1 may act as a "double edge sword" in the regulation of β cell mass and function in response to metabolic stress such as nutrient overload and insulin resistance. Read More

    Inactivation of the Glucose-Dependent Insulinotropic Polypeptide Receptor Improves Outcomes following Experimental Myocardial Infarction.
    Cell Metab 2018 Feb 21;27(2):450-460.e6. Epub 2017 Dec 21.
    Lunenfeld Tanenbaum Research Institute, Mount Sinai Hospital, University of Toronto, Toronto, ON M5G 1X5, Canada. Electronic address:
    Incretin hormones exert pleiotropic metabolic actions beyond the pancreas. Although the heart expresses both incretin receptors, the cardiac biology of GIP receptor (GIPR) action remains incompletely understood. Here we show that GIPR agonism did not impair the response to cardiac ischemia. Read More

    mTORC1 Inactivation Promotes Colitis-Induced Colorectal Cancer but Protects from APC Loss-Dependent Tumorigenesis.
    Cell Metab 2018 Jan 21;27(1):118-135.e8. Epub 2017 Dec 21.
    Cancer Cell Biology Programme, Growth Factors, Nutrients and Cancer Group, Centro Nacional de Investigaciones Oncológicas, CNIO, Madrid 28029, Spain. Electronic address:
    Dietary habits that can induce inflammatory bowel disease (IBD) are major colorectal cancer (CRC) risk factors, but mechanisms linking nutrients, IBD, and CRC are unknown. Using human data and mouse models, we show that mTORC1 inactivation-induced chromosomal instability impairs intestinal crypt proliferation and regeneration, CDK4/6 dependently. This triggers interleukin (IL)-6-associated reparative inflammation, inducing crypt hyper-proliferation, wound healing, and CRC. Read More

    JAK/STAT3-Regulated Fatty Acid β-Oxidation Is Critical for Breast Cancer Stem Cell Self-Renewal and Chemoresistance.
    Cell Metab 2018 Jan 14;27(1):136-150.e5. Epub 2017 Dec 14.
    Department of Immuno-Oncology, Beckman Research Institute and City of Hope Comprehensive Cancer Center, Duarte, CA 91010, USA. Electronic address:
    Cancer stem cells (CSCs) are critical for cancer progression and chemoresistance. How lipid metabolism regulates CSCs and chemoresistance remains elusive. Here, we demonstrate that JAK/STAT3 regulates lipid metabolism, which promotes breast CSCs (BCSCs) and cancer chemoresistance. Read More

    NADIntermediates: The Biology and Therapeutic Potential of NMN and NR.
    Cell Metab 2017 Dec 14. Epub 2017 Dec 14.
    Department of Developmental Biology, Department of Medicine (Joint), Washington University School of Medicine, Campus Box 8103, 660 South Euclid Avenue, St. Louis, MO 63110, USA; Japan Agency for Medical Research and Development, Project for Elucidating and Controlling Mechanisms of Aging and Longevity, Tokyo, Japan. Electronic address:
    Research on the biology of NADhas been gaining momentum, providing many critical insights into the pathogenesis of age-associated functional decline and diseases. In particular, two key NADintermediates, nicotinamide riboside (NR) and nicotinamide mononucleotide (NMN), have been extensively studied over the past several years. Supplementing these NADintermediates has shown preventive and therapeutic effects, ameliorating age-associated pathophysiologies and disease conditions. Read More

    LEAP2 Is an Endogenous Antagonist of the Ghrelin Receptor.
    Cell Metab 2018 Feb 7;27(2):461-469.e6. Epub 2017 Dec 7.
    NGM Biopharmaceuticals, South San Francisco, CA 94080, USA. Electronic address:
    Ghrelin, an appetite-stimulatory hormone secreted by the stomach, was discovered as a ligand for the growth hormone secretagogue receptor (GHSR). Through GHSR, ghrelin stimulates growth hormone (GH) secretion, a function that evolved to protect against starvation-induced hypoglycemia. Though the biology mediated by ghrelin has been described in great detail, regulation of ghrelin action is poorly understood. Read More

    MAIT Cells: A Link between Gut Integrity and Type 1 Diabetes.
    Cell Metab 2017 Dec;26(6):813-815
    Department of Immunobiology, Yale University, New Haven, CT 06520, USA. Electronic address:
    Type 1 diabetes (T1D) is a multifactorial autoimmune disease whose etiology involves complex interactions between the immune system and the intestinal microbiota. Recent studies by Rouxel et al. (2017) suggest that innate-like mucosal-associated invariant T cells (MAIT cells) may link gut integrity, the microbiota, and T1D. Read More

    When Cancer Cells Are Given Lemo[NH]s, They Make Lemo[NH]ade.
    Cell Metab 2017 Dec;26(6):811-813
    Department of Molecular and Integrative Physiology, University of Michigan, Ann Arbor, MI 48109, USA; Department of Internal Medicine, Division of Gastroenterology, University of Michigan, Ann Arbor, MI 48109, USA. Electronic address:
    In normal physiology, end-products of metabolism are excreted from the body. In tumors, these metabolic wastes accumulate due to deregulated metabolism and vascular insufficiency. Spinelli et al. Read More

    Transcriptional Noise and Somatic Mutations in the Aging Pancreas.
    Cell Metab 2017 Dec;26(6):809-811
    Department of Developmental Biology and Cancer Research, The Institute for Medical Research Israel-Canada, The Hebrew University-Hadassah Medical School, Jerusalem, Israel. Electronic address:
    The underlying mechanisms and functional significance of pancreatic β cell heterogeneity are an intensive area of investigation. In a recent Cell paper, Enge and colleagues (2017) performed single-cell RNA sequencing of human pancreatic cells and concluded that with age, pancreatic cells become transcriptionally noisy and accumulate somatic mutations. Read More

    RevAMPing Mitochondrial Shape to Live Longer.
    Cell Metab 2017 Dec;26(6):805-806
    Department of Biology, University of Padova, Via U. Bassi 58B, 35121 Padova, Italy; Venetian Institute of Molecular Medicine, Via Orus 2, 35129 Padova, Italy. Electronic address:
    Whether and how mitochondria connect reduced energy intake to healthy aging are unclear. In this issue of Cell Metabolism, Weir et al. (2017) find that constitutive AMPK activation and dietary restriction promote longevity in C. Read More

    Sensing and Transmitting Intracellular Amino Acid Signals through Reversible Lysine Aminoacylations.
    Cell Metab 2018 Jan 30;27(1):151-166.e6. Epub 2017 Nov 30.
    Obstetrics and Gynecology Hospital of Fudan University, State Key Lab of Genetic Engineering, School of Life Sciences and Institutes of Biomedical Sciences, Fudan University, Shanghai 200032, PRC; Key Laboratory of Reproduction Regulation of NPFPC (SIPPR,IRD) and Collaborative Innovation Center for Genetics and Development, Fudan University, Shanghai 200032, PRC; State Key Laboratory of Biotherapy/ Collaborative Innovation Center for Biotherapy, West China Hospital, Sichuan University, Chengdu 610041, PRC. Electronic address:
    Amino acids are known regulators of cellular signaling and physiology, but how they are sensed intracellularly is not fully understood. Herein, we report that each aminoacyl-tRNA synthetase (ARS) senses its cognate amino acid sufficiency through catalyzing the formation of lysine aminoacylation (K-AA) on its specific substrate proteins. At physiologic levels, amino acids promote ARSs bound to their substrates and form K-AAs on the ɛ-amine of lysines in their substrates by producing reactive aminoacyl adenylates. Read More

    GDF15-From Biomarker to Allostatic Hormone.
    Cell Metab 2017 Dec 28;26(6):807-808. Epub 2017 Nov 28.
    MRC Metabolic Diseases Unit and Metabolic Research Laboratories, Wellcome Trust-MRC Institute of Metabolic Science, University of Cambridge, Addenbrooke's Hospital, Cambridge CB2 0QQ, UK. Electronic address:
    With the identification of its receptor in a highly specific region of the brain, interesting issues come to light regarding the normal physiological functions of GDF15, a secreted protein long identified as a biomarker of diverse disease states. Read More

    AMPK: Sensing Glucose as well as Cellular Energy Status.
    Cell Metab 2018 Feb 16;27(2):299-313. Epub 2017 Nov 16.
    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 2018 Jan 16;27(1):195-209.e6. Epub 2017 Nov 16.
    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-NADAxis Regulates Immunotherapeutic Anti-Tumor T Cell Response.
    Cell Metab 2018 Jan 9;27(1):85-100.e8. Epub 2017 Nov 9.
    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 2018 Jan 9;27(1):210-217.e3. Epub 2017 Nov 9.
    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 (V), explained by a reduction in hepatic acetyl-CoA content, and net hepatic glycogenolysis. Read More

    Advances in Hypoxia-Inducible Factor Biology.
    Cell Metab 2018 Feb 9;27(2):281-298. Epub 2017 Nov 9.
    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

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