2,954 results match your criteria Cell Metab.[Journal]


Omics-Driven Systems Interrogation of Metabolic Dysregulation in COVID-19 Pathogenesis.

Cell Metab 2020 Jun 24. Epub 2020 Jun 24.

State Key Laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing 100101, China. Electronic address:

The coronavirus disease 2019 (COVID-19) pandemic presents an unprecedented threat to global public health. Herein, we utilized a combination of targeted and untargeted tandem mass spectrometry to analyze the plasma lipidome and metabolome in mild, moderate, and severe COVID-19 patients and healthy controls. A panel of 10 plasma metabolites effectively distinguished COVID-19 patients from healthy controls (AUC = 0. Read More

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http://dx.doi.org/10.1016/j.cmet.2020.06.016DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7311890PMC

A Universal Gut-Microbiome-Derived Signature Predicts Cirrhosis.

Cell Metab 2020 Jun 24. Epub 2020 Jun 24.

NAFLD Research Center, Department of Medicine, University of California, San Diego, La Jolla, CA 92093, USA; Division of Epidemiology, Department of Family and Preventative Medicine, University of California, San Diego, La Jolla, CA 92093, USA; Division of Gastroenterology, Department of Medicine, University of California, San Diego, La Jolla, CA 92093, USA. Electronic address:

Dysregulation of the gut microbiome has been implicated in the progression of non-alcoholic fatty liver disease (NAFLD) to advanced fibrosis and cirrhosis. To determine the diagnostic capacity of this association, we compared stool microbiomes across 163 well-characterized participants encompassing non-NAFLD controls, NAFLD-cirrhosis patients, and their first-degree relatives. Interrogation of shotgun metagenomic and untargeted metabolomic profiles by using the random forest machine learning algorithm and differential abundance analysis identified discrete metagenomic and metabolomic signatures that were similarly effective in detecting cirrhosis (diagnostic accuracy 0. Read More

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http://dx.doi.org/10.1016/j.cmet.2020.06.005DOI Listing

In-Hospital Use of Statins Is Associated with a Reduced Risk of Mortality among Individuals with COVID-19.

Cell Metab 2020 Jun 24. Epub 2020 Jun 24.

Department of Cardiology, Renmin Hospital, School of Basic Medical Science, Wuhan University, Wuhan, China; Institute of Model Animal, Wuhan University, Wuhan, China; Medical Science Research Center, Zhongnan Hospital of Wuhan University, Wuhan, China; Department of Hepatobiliary and Pancreatic Surgery, Zhongnan Hospital of Wuhan University, Wuhan, China. Electronic address:

Statins are lipid-lowering therapeutics with favorable anti-inflammatory profiles and have been proposed as an adjunct therapy for COVID-19. However, statins may increase the risk of SARS-CoV-2 viral entry by inducing ACE2 expression. Here, we performed a retrospective study on 13,981 patients with COVID-19 in Hubei Province, China, among which 1,219 received statins. Read More

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http://dx.doi.org/10.1016/j.cmet.2020.06.015DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7311917PMC

Age-Induced Reduction in Human Lipolysis: A Potential Role for Adipocyte Noradrenaline Degradation.

Cell Metab 2020 Jun 19. Epub 2020 Jun 19.

Department of Medicine (H7), Karolinska Institutet, Karolinska University Hospital, Huddinge, 141 86 Stockholm, Sweden. Electronic address:

Gao et al. report that the observed reduction in adipose lipolysis with age in women could be explained by an upregulation of the catecholamine-degradation pathway in subcutaneous adipocytes. However, in contrast to findings in mice, these pathways are enriched in adipocytes and not in immune cells, suggesting species-specific differences in aging mechanisms. Read More

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http://dx.doi.org/10.1016/j.cmet.2020.06.007DOI Listing

Adenosine/A2B Receptor Signaling Ameliorates the Effects of Aging and Counteracts Obesity.

Cell Metab 2020 Jun 22. Epub 2020 Jun 22.

Institute of Pharmacology and Toxicology, University Hospital, University of Bonn, 53127 Bonn, Germany. Electronic address:

The combination of aging populations with the obesity pandemic results in an alarming rise in non-communicable diseases. Here, we show that the enigmatic adenosine A2B receptor (A2B) is abundantly expressed in skeletal muscle (SKM) as well as brown adipose tissue (BAT) and might be targeted to counteract age-related muscle atrophy (sarcopenia) as well as obesity. Mice with SKM-specific deletion of A2B exhibited sarcopenia, diminished muscle strength, and reduced energy expenditure (EE), whereas pharmacological A2B activation counteracted these processes. Read More

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http://dx.doi.org/10.1016/j.cmet.2020.06.006DOI Listing

NAD+ Regeneration Rescues Lifespan, but Not Ataxia, in a Mouse Model of Brain Mitochondrial Complex I Dysfunction.

Cell Metab 2020 Jun 16. Epub 2020 Jun 16.

Northwestern University Feinberg School of Medicine, Department of Medicine Division of Pulmonary and Critical Care Medicine, Chicago, IL 60611, USA; Northwestern University Feinberg School of Medicine, Department of Biochemistry and Molecular Genetics, Chicago, IL 60611, USA. Electronic address:

Mitochondrial complex I regenerates NAD+ and proton pumps for TCA cycle function and ATP production, respectively. Mitochondrial complex I dysfunction has been implicated in many brain pathologies including Leigh syndrome and Parkinson's disease. We sought to determine whether NAD+ regeneration or proton pumping, i. Read More

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http://dx.doi.org/10.1016/j.cmet.2020.06.003DOI Listing

Small Extracellular Vesicles Have GST Activity and Ameliorate Senescence-Related Tissue Damage.

Cell Metab 2020 Jun 17. Epub 2020 Jun 17.

Epigenetics & Cellular Senescence Group, Blizard Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, 4 Newark Street, London E1 2AT, UK. Electronic address:

Aging is a process of cellular and tissue dysfunction characterized by different hallmarks, including cellular senescence. However, there is proof that certain features of aging and senescence can be ameliorated. Here, we provide evidence that small extracellular vesicles (sEVs) isolated from primary fibroblasts of young human donors ameliorate certain biomarkers of senescence in cells derived from old and Hutchinson-Gilford progeria syndrome donors. Read More

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http://dx.doi.org/10.1016/j.cmet.2020.06.004DOI Listing

Targeting DGAT1 Ameliorates Glioblastoma by Increasing Fat Catabolism and Oxidative Stress.

Cell Metab 2020 Jun 9. Epub 2020 Jun 9.

Department of Radiation Oncology, James Comprehensive Cancer Center and College of Medicine at The Ohio State University, Columbus, OH 43210, USA; Center for Cancer Metabolism, James Comprehensive Cancer Center at The Ohio State University, Columbus, OH 43210, USA. Electronic address:

Glioblastoma (GBM), a mostly lethal brain tumor, acquires large amounts of free fatty acids (FAs) to promote cell growth. But how the cancer avoids lipotoxicity is unknown. Here, we identify that GBM upregulates diacylglycerol-acyltransferase 1 (DGAT1) to store excess FAs into triglycerides and lipid droplets. Read More

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http://dx.doi.org/10.1016/j.cmet.2020.06.002DOI Listing
June 2020
17.565 Impact Factor

Oligodendrocytes Provide Antioxidant Defense Function for Neurons by Secreting Ferritin Heavy Chain.

Cell Metab 2020 Jun 5. Epub 2020 Jun 5.

Institute of Neuronal Cell Biology, Technical University Munich, 80802 Munich, Germany; German Center for Neurodegenerative Diseases (DZNE), 81377 Munich, Germany; Max Planck Institute of Experimental Medicine, 37075 Göttingen, Germany; Munich Cluster of Systems Neurology (SyNergy), 81377 Munich, Germany. Electronic address:

An evolutionarily conserved function of glia is to provide metabolic and structural support for neurons. To identify molecules generated by glia and with vital functions for neurons, we used Drosophila melanogaster as a screening tool, and subsequently translated the findings to mice. We found that a cargo receptor operating in the secretory pathway of glia was essential to maintain axonal integrity by regulating iron buffering. Read More

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http://dx.doi.org/10.1016/j.cmet.2020.05.019DOI Listing

Local Mitochondrial ATP Production Regulates Endothelial Fatty Acid Uptake and Transport.

Cell Metab 2020 Jun 2. Epub 2020 Jun 2.

Cardiovascular Institute, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA. Electronic address:

Most organs use fatty acids (FAs) as a key nutrient, but little is known of how blood-borne FAs traverse the endothelium to reach underlying tissues. We conducted a small-molecule screen and identified niclosamide as a suppressor of endothelial FA uptake and transport. Structure/activity relationship studies demonstrated that niclosamide acts through mitochondrial uncoupling. Read More

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http://dx.doi.org/10.1016/j.cmet.2020.05.018DOI Listing

Toll-Like Receptors Induce Signal-Specific Reprogramming of the Macrophage Lipidome.

Cell Metab 2020 May 30. Epub 2020 May 30.

Department of Microbiology, Immunology and Molecular Genetics, University of California, Los Angeles, CA 90095, USA; Department of Molecular and Medical Pharmacology, David Geffen School of Medicine, University of California, Los Angeles, CA 90095, USA. Electronic address:

Macrophages reprogram their lipid metabolism in response to activation signals. However, a systems-level understanding of how different pro-inflammatory stimuli reshape the macrophage lipidome is lacking. Here, we use complementary "shotgun" and isotope tracer mass spectrometry approaches to define the changes in lipid biosynthesis, import, and composition of macrophages induced by various Toll-like receptors (TLRs) and inflammatory cytokines. Read More

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http://dx.doi.org/10.1016/j.cmet.2020.05.003DOI Listing

Distinct iNKT Cell Populations Use IFNγ or ER Stress-Induced IL-10 to Control Adipose Tissue Homeostasis.

Cell Metab 2020 Jun 5. Epub 2020 Jun 5.

Division of Rheumatology, Inflammation, and Immunity, Brigham and Women's Hospital, Boston, MA, USA; Program in Immunology, Harvard Medical School, Boston, MA, USA; Department of Medicine, Brigham and Women's Hospital, Boston, MA, USA. Electronic address:

Adipose tissue invariant natural killer T (iNKT) cells are phenotypically different from other iNKT cells because they produce IL-10 and control metabolic homeostasis. Why that is the case is unclear. Here, using single-cell RNA sequencing, we found several adipose iNKT clusters, which we grouped into two functional populations based on NK1. Read More

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http://dx.doi.org/10.1016/j.cmet.2020.05.017DOI Listing

Deletion of Fructokinase in the Liver or in the Intestine Reveals Differential Effects on Sugar-Induced Metabolic Dysfunction.

Cell Metab 2020 May 28. Epub 2020 May 28.

University of Colorado, Division of Renal Diseases and Hypertension, University of Colorado School of Medicine, Aurora, CO, USA. Electronic address:

Intake of fructose-containing sugars is strongly associated with metabolic syndrome. Compared with other sugars, dietary fructose is uniquely metabolized by fructokinase. However, the tissue-specific role of fructokinase in sugar-induced metabolic syndrome, and the specific roles of glucose and fructose in driving it, is not fully understood. Read More

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http://dx.doi.org/10.1016/j.cmet.2020.05.012DOI Listing

The Major Pre- and Postmenopausal Estrogens Play Opposing Roles in Obesity-Driven Mammary Inflammation and Breast Cancer Development.

Cell Metab 2020 Jun;31(6):1154-1172.e9

Braman Family Breast Cancer Institute, Sylvester Comprehensive Cancer Center, Miami, FL 33136, USA; Department of Medicine, Miller School of Medicine, University of Miami, Miami, FL, USA; Department of Biochemistry and Molecular Biology, Miller School of Medicine, University of Miami, Miami, FL, USA. Electronic address:

Many inflammation-associated diseases, including cancers, increase in women after menopause and with obesity. In contrast to anti-inflammatory actions of 17β-estradiol, we find estrone, which dominates after menopause, is pro-inflammatory. In human mammary adipocytes, cytokine expression increases with obesity, menopause, and cancer. Read More

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http://dx.doi.org/10.1016/j.cmet.2020.05.008DOI Listing
June 2020
17.565 Impact Factor

Endothelial Lactate Controls Muscle Regeneration from Ischemia by Inducing M2-like Macrophage Polarization.

Cell Metab 2020 Jun;31(6):1136-1153.e7

Laboratory of Exercise and Health, Department Health Sciences and Technology, Swiss Federal Institute of Technology (ETH) Zurich, 8603 Zurich, Switzerland. Electronic address:

Endothelial cell (EC)-derived signals contribute to organ regeneration, but angiocrine metabolic communication is not described. We found that EC-specific loss of the glycolytic regulator pfkfb3 reduced ischemic hindlimb revascularization and impaired muscle regeneration. This was caused by the reduced ability of macrophages to adopt a proangiogenic and proregenerative M2-like phenotype. Read More

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http://dx.doi.org/10.1016/j.cmet.2020.05.004DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7267778PMC

Exome Sequencing Identifies Genes and Gene Sets Contributing to Severe Childhood Obesity, Linking PHIP Variants to Repressed POMC Transcription.

Cell Metab 2020 Jun;31(6):1107-1119.e12

Wellcome Sanger Institute, Cambridge, UK; University of Cambridge MRC Epidemiology Unit, Wellcome Trust-MRC Institute of Metabolic Science, Addenbrooke's Hospital, Cambridge, UK. Electronic address:

Obesity is genetically heterogeneous with monogenic and complex polygenic forms. Using exome and targeted sequencing in 2,737 severely obese cases and 6,704 controls, we identified three genes (PHIP, DGKI, and ZMYM4) with an excess burden of very rare predicted deleterious variants in cases. In cells, we found that nuclear PHIP (pleckstrin homology domain interacting protein) directly enhances transcription of pro-opiomelanocortin (POMC), a neuropeptide that suppresses appetite. Read More

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http://dx.doi.org/10.1016/j.cmet.2020.05.007DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7267775PMC

Ketone Bodies Exert Ester-Ordinary Suppression of Bifidobacteria and Th17 Cells.

Cell Metab 2020 Jun;31(6):1049-1051

Department of Integrative Biology and Physiology, University of California, Los Angeles, Los Angeles, CA 90095, USA. Electronic address:

The ketogenic diet is used to treat neurological and metabolic symptoms of disease, but the extent of its influences across organ systems remains unclear. Ang et al., 2020 reveal that ketone bodies induced by the diet inhibit specific bacteria of the gut microbiota and suppress pro-inflammatory T cells in the intestine. Read More

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http://dx.doi.org/10.1016/j.cmet.2020.05.011DOI Listing

Break on Through: Golgi-Derived Vesicles Aid in Mitochondrial Fission.

Cell Metab 2020 Jun;31(6):1047-1049

Department of Cell and Developmental Biology, Vanderbilt University, Nashville, TN, USA; Vanderbilt Center for Stem Cell Biology, Vanderbilt University, Nashville, TN, USA; Vanderbilt Brain Institute, Vanderbilt University, Nashville, TN, USA. Electronic address:

Mitochondrial fission is sustained through contact with several organelles, including the endoplasmic reticulum, lysosomes, and the actin cytoskeleton. Nagashima et al. (2020) now demonstrate that PI(4)P-containing Golgi-derived vesicles also modulate mitochondrial fission, driven by Arf1 and PI(4)KIIIβ activity, identifying a new organelle contact involved in maintaining mitochondrial homeostasis. Read More

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http://dx.doi.org/10.1016/j.cmet.2020.05.010DOI Listing

Pseudomonas Persists by Feeding off Itaconate.

Cell Metab 2020 Jun;31(6):1045-1047

School of Biochemistry and Immunology, Trinity Biomedical Sciences Institute, Trinity College Dublin, 152-160 Pearse Street, Dublin D02R590, Ireland. Electronic address:

Itaconate is an immunometabolite with anti-inflammatory and anti-microbial properties. Riquelme et al. (2020) demonstrate that pathogenic Pseudomonas aeruginosa drives itaconate production by macrophages, which it then uses as a carbon source for biofilm formation, allowing it to persist during infection and suppress inflammation. Read More

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http://dx.doi.org/10.1016/j.cmet.2020.05.005DOI Listing

A Sympathetic Treatment for Obesity.

Cell Metab 2020 Jun;31(6):1043-1045

Program in Cell Signaling and Neurobiology of Metabolism, Yale University School of Medicine, New Haven, CT 06520, USA; Departments of Cellular and Molecular Physiology, Yale University School of Medicine, New Haven, CT 06520, USA; Department of Comparative Medicine, Yale University School of Medicine, New Haven, CT 06520, USA; Department of Neuroscience, Yale University School of Medicine, New Haven, CT 06520, USA. Electronic address:

Amphetamine (AMPH), mainly used in the treatment of attention deficit hyperactivity disorder and narcolepsy, has weight loss properties, although with detrimental cardiovascular effects. In this issue, Mahú et al. (2020) describe the effect of a new derivative of AMPH, "PEGyAMPH," a brain-spared anti-obesity drug that alters sympathetic activity without cardiovascular side effects. Read More

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http://dx.doi.org/10.1016/j.cmet.2020.05.009DOI Listing

Of Mice and Men: NAD Boosting with Niacin Provides Hope for Mitochondrial Myopathy Patients.

Cell Metab 2020 Jun;31(6):1041-1043

Department of Anesthesiology and Experimental Therapeutics, Kogod Center on Aging and Co-director of Mayo Clinic Mitochondrial Research Center, Mayo Clinic, Rochester, MN 55905, USA. Electronic address:

In this issue of Cell Metabolism, Pirinen et al. (2020) show that disruption in NAD homeostasis is a key component of the pathogenesis of mitochondrial myopathy in humans that can be targeted by the administration of the NAD precursor niacin, identifying NAD boosting as a potential treatment for this devastating disease. Read More

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http://dx.doi.org/10.1016/j.cmet.2020.05.013DOI Listing

Voices: The Author's Journey.

Authors:

Cell Metab 2020 Jun;31(6):1037-1040

In the era of a pandemic, networking opportunities have evaporated, and researchers are reinventing ways to connect with the community. It is our pleasure to build some of those connections, especially for young authors, by introducing you to eleven scientists whose work is featured in this issue. Here, they share their diverse and splendid journeys-from early concepts to the fruition of published work. Read More

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http://dx.doi.org/10.1016/j.cmet.2020.05.014DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7265860PMC

Voices: Meet the Advisory Board.

Authors:

Cell Metab 2020 Jun;31(6):1035-1036

We are excited to announce that the Cell Metabolism Advisory Board has grown to better represent the metabolism community. We are honored to present these leaders as they share their perspectives. From taking unexpected journeys to pushing for a stronger future, they emphasize the indisputable value of curiosity, teamwork, diversity, and support. Read More

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http://dx.doi.org/10.1016/j.cmet.2020.05.015DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7265839PMC

Valuing Diversity.

Cell Metab 2020 Jun;31(6):1033-1034

Editor-in-Chief, Cell Metabolism.

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http://dx.doi.org/10.1016/j.cmet.2020.05.016DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7265968PMC

Defined p16 Senescent Cell Types Are Indispensable for Mouse Healthspan.

Cell Metab 2020 May 26. Epub 2020 May 26.

Institute for Research on Cancer and Aging of Nice (IRCAN), INSERM, Université Côte d'Azur, Centre National de la Recherche Scientifique (CNRS), Nice, France. Electronic address:

The accumulation of senescent cells can drive many age-associated phenotypes and pathologies. Consequently, it has been proposed that removing senescent cells might extend lifespan. Here, we generated two knockin mouse models targeting the best-characterized marker of senescence, p16. Read More

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http://dx.doi.org/10.1016/j.cmet.2020.05.002DOI Listing

A Metabolic Roadmap for Somatic Stem Cell Fate.

Cell Metab 2020 Jun 19;31(6):1052-1067. Epub 2020 May 19.

Centre for Muscle Research, Department of Physiology, The University of Melbourne, Melbourne, VIC 3010, Australia. Electronic address:

While metabolism was initially thought to play a passive role in cell biology by generating ATP to meet bioenergetic demands, recent studies have identified critical roles for metabolism in the generation of new biomass and provision of obligate substrates for the epigenetic modification of histones and DNA. This review details how metabolites generated through glycolysis and the tricarboxylic acid cycle are utilized by somatic stem cells to support cell proliferation and lineage commitment. Importantly, we also discuss the evolving hypothesis that histones can act as an energy reservoir during times of energy stress. Read More

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http://dx.doi.org/10.1016/j.cmet.2020.04.022DOI Listing

GLP-1 Receptor Signaling in Astrocytes Regulates Fatty Acid Oxidation, Mitochondrial Integrity, and Function.

Cell Metab 2020 Jun 19;31(6):1189-1205.e13. Epub 2020 May 19.

Max Planck Institute for Metabolism Research, Department of Neuronal Control of Metabolism, Gleueler Str. 50, 50931 Cologne, Germany; Center for Endocrinology, Diabetes and Preventive Medicine (CEDP), University Hospital Cologne, Kerpener Str. 26, 50924 Cologne, Germany; Excellence Cluster on Cellular Stress Responses in Aging Associated Diseases (CECAD) and Center of Molecular Medicine Cologne (CMMC), University of Cologne, Joseph-Stelzmann-Str. 26, 50931 Cologne, Germany; National Center for Diabetes Research (DZD), Ingolstädter Landstrasse 1, 85764 Neuherberg, Germany. Electronic address:

Astrocytes represent central regulators of brain glucose metabolism and neuronal function. They have recently been shown to adapt their function in response to alterations in nutritional state through responding to the energy state-sensing hormones leptin and insulin. Here, we demonstrate that glucagon-like peptide (GLP)-1 inhibits glucose uptake and promotes β-oxidation in cultured astrocytes. Read More

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http://dx.doi.org/10.1016/j.cmet.2020.05.001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7272126PMC

Pseudomonas aeruginosa Utilizes Host-Derived Itaconate to Redirect Its Metabolism to Promote Biofilm Formation.

Cell Metab 2020 Jun 18;31(6):1091-1106.e6. Epub 2020 May 18.

Department of Pediatrics, Columbia University, New York, NY 10032, USA. Electronic address:

The bacterium Pseudomonas aeruginosa is especially pathogenic, often being associated with intractable pneumonia and high mortality. How P. aeruginosa avoids immune clearance and persists in the inflamed human airway remains poorly understood. Read More

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http://dx.doi.org/10.1016/j.cmet.2020.04.017DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7272298PMC

Positive Reinforcing Mechanisms between GPR120 and PPARγ Modulate Insulin Sensitivity.

Cell Metab 2020 Jun 14;31(6):1173-1188.e5. Epub 2020 May 14.

Touchstone Diabetes Center, Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA; Division of Endocrinology and Metabolism, Department of Medicine, University of California, San Diego, La Jolla, CA 92093, USA. Electronic address:

G protein-coupled receptor 120 (GPR120) and PPARγ agonists each have insulin sensitizing effects. But whether these two pathways functionally interact and can be leveraged together to markedly improve insulin resistance has not been explored. Here, we show that treatment with the PPARγ agonist rosiglitazone (Rosi) plus the GPR120 agonist Compound A leads to additive effects to improve glucose tolerance and insulin sensitivity, but at lower doses of Rosi, thus avoiding its known side effects. Read More

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http://dx.doi.org/10.1016/j.cmet.2020.04.020DOI Listing

Untangling Determinants of Enhanced Health and Lifespan through a Multi-omics Approach in Mice.

Cell Metab 2020 May 11. Epub 2020 May 11.

Translational Gerontology Branch, National Institute on Aging, National Institutes of Health, Baltimore, MD 21224, USA. Electronic address:

The impact of chronic caloric restriction (CR) on health and survival is complex with poorly understood underlying molecular mechanisms. A recent study in mice addressing the diets used in nonhuman primate CR studies found that while diet composition did not impact longevity, fasting time and total calorie intake were determinant for increased survival. Here, integrated analysis of physiological and multi-omics data from ad libitum, meal-fed, or CR animals was used to gain insight into pathways associated with improved health and survival. Read More

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http://dx.doi.org/10.1016/j.cmet.2020.04.018DOI Listing

Disulfiram Treatment Normalizes Body Weight in Obese Mice.

Cell Metab 2020 May 7. Epub 2020 May 7.

Experimental Gerontology Section, Translational Gerontology Branch, National Institute on Aging, National Institutes of Health, Baltimore, MD 21224, USA. Electronic address:

Obesity is a top public health concern, and a molecule that safely treats obesity is urgently needed. Disulfiram (known commercially as Antabuse), an FDA-approved treatment for chronic alcohol addiction, exhibits anti-inflammatory properties and helps protect against certain types of cancer. Here, we show that in mice disulfiram treatment prevented body weight gain and abrogated the adverse impact of an obesogenic diet on insulin responsiveness while mitigating liver steatosis and pancreatic islet hypertrophy. Read More

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http://dx.doi.org/10.1016/j.cmet.2020.04.019DOI Listing
May 2020
17.565 Impact Factor

Metformin Enhances Autophagy and Normalizes Mitochondrial Function to Alleviate Aging-Associated Inflammation.

Cell Metab 2020 May 5. Epub 2020 May 5.

Department of Pharmacology and Nutritional Sciences, University of Kentucky, Lexington, KY, USA; Barnstable Brown Diabetes and Obesity Center, University of Kentucky, Lexington, KY, USA. Electronic address:

Age is a non-modifiable risk factor for the inflammation that underlies age-associated diseases; thus, anti-inflammaging drugs hold promise for increasing health span. Cytokine profiling and bioinformatic analyses showed that Th17 cytokine production differentiates CD4 T cells from lean, normoglycemic older and younger subjects, and mimics a diabetes-associated Th17 profile. T cells from older compared to younger subjects also had defects in autophagy and mitochondrial bioenergetics that associate with redox imbalance. Read More

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http://dx.doi.org/10.1016/j.cmet.2020.04.015DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7217133PMC
May 2020
17.565 Impact Factor

Brain-Sparing Sympathofacilitators Mitigate Obesity without Adverse Cardiovascular Effects.

Cell Metab 2020 Jun 12;31(6):1120-1135.e7. Epub 2020 May 12.

Department of Physiology, Anatomy and Genetics, University of Oxford, Parks Road, Oxford OX1 3PT, UK; Obesity Laboratory, Instituto Gulbenkian de Ciência, Oeiras 2780-156, Portugal; Howard Hughes Medical Institute, IGC, Oeiras, Portugal. Electronic address:

Anti-obesity drugs in the amphetamine (AMPH) class act in the brain to reduce appetite and increase locomotion. They are also characterized by adverse cardiovascular effects with origin that, despite absence of any in vivo evidence, is attributed to a direct sympathomimetic action in the heart. Here, we show that the cardiac side effects of AMPH originate from the brain and can be circumvented by PEGylation (PEGyAMPH) to exclude its central action. Read More

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http://dx.doi.org/10.1016/j.cmet.2020.04.013DOI Listing

CD4 T Cells at the Center of Inflammaging.

Cell Metab 2020 Apr 25. Epub 2020 Apr 25.

Suzhou Institute for Systems Medicine, Chinese Academy of Medical Sciences, Suzhou, China; Faculty of Medicine, Université Paris Saclay, Le Kremlin-Bicêtre, France; Gustave Roussy Comprehensive Cancer Institute, Villejuif, France; INSERM U1015, Villejuif, France; Center of Clinical Investigations in Biotherapies of Cancer (CICBT) 1428, Villejuif, France.

Bharath et al., 2020 report that CD4 T lymphocytes from aged individuals exhibit defective mitochondrial autophagy, resulting in altered redox metabolism and upregulation of TH17 cytokines, which in turn may contribute to aging-associated chronic inflammation or "inflammaging." Of note, the antiaging drug metformin reverses this autophagy defect and rejuvenates CD4 T cell function. Read More

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http://dx.doi.org/10.1016/j.cmet.2020.04.016DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7217078PMC

Niacin Cures Systemic NAD Deficiency and Improves Muscle Performance in Adult-Onset Mitochondrial Myopathy.

Cell Metab 2020 Jun 7;31(6):1078-1090.e5. Epub 2020 May 7.

Research Program of Stem Cells and Metabolism, Faculty of Medicine, University of Helsinki, Helsinki 00290, Finland; HUSlab, Helsinki University Hospital, Helsinki 00290, Finland; Neuroscience Center, HiLife, University of Helsinki, Helsinki 00290, Finland. Electronic address:

NAD is a redox-active metabolite, the depletion of which has been proposed to promote aging and degenerative diseases in rodents. However, whether NAD depletion occurs in patients with degenerative disorders and whether NAD repletion improves their symptoms has remained open. Here, we report systemic NAD deficiency in adult-onset mitochondrial myopathy patients. Read More

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http://dx.doi.org/10.1016/j.cmet.2020.04.008DOI Listing

Low-Dose Sorafenib Acts as a Mitochondrial Uncoupler and Ameliorates Nonalcoholic Steatohepatitis.

Cell Metab 2020 May;31(5):892-908.e11

Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan 430060, China; Institute of Model Animal of Wuhan University, Wuhan 430071, China; Medical Science Research Center, Zhongnan Hospital of Wuhan University, Wuhan 430071, China; School of Basic Medical Sciences, Wuhan University, Wuhan 430071, China. Electronic address:

Nonalcoholic steatohepatitis (NASH) is becoming one of the leading causes of hepatocellular carcinoma (HCC). Sorafenib is the only first-line therapy for advanced HCC despite its serious adverse effects. Here, we report that at an equivalent of approximately one-tenth the clinical dose for HCC, sorafenib treatment effectively prevents the progression of NASH in both mice and monkeys without any observed significant adverse events. Read More

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http://dx.doi.org/10.1016/j.cmet.2020.04.011DOI Listing
May 2020
17.565 Impact Factor

Dietary Fat Makes Germinal Center B Cells Happy.

Authors:
Shuai Jiang

Cell Metab 2020 May;31(5):890-891

Department of Microbiology and Immunology, Louisiana State University Health Sciences Center, Shreveport, LA 71130, USA. Electronic address:

It is unclear whether ex vivo bona fide distinct types of lymphocytes require the availability of different nutrients in the extracellular environment to support cell growth upon activation. Weisel et al. (2020) recently identified fatty acids as a predominant energy source for ex vivo bona fide germinal center B cell growth. Read More

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http://dx.doi.org/10.1016/j.cmet.2020.04.010DOI Listing

From the Transcriptome to Electrophysiology: Searching for the Underlying Cause of Diabetes.

Cell Metab 2020 May;31(5):888-889

Department of Bioengineering, University of Colorado Anschutz Medical Campus, Aurora, CO, USA; Barbara Davis Center of Childhood Diabetes, University of Colorado Anschutz Medical Campus, Aurora, CO, USA. Electronic address:

Cells within the islet of Langerhans are heterogeneous. Camunas-Soler et al. (2020) implement a patch-seq technique to collect both transcriptomic and electrophysiological data from the same cell. Read More

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http://dx.doi.org/10.1016/j.cmet.2020.04.012DOI Listing

OPA1 and Angiogenesis: Beyond the Fusion Function.

Cell Metab 2020 May;31(5):886-887

Department of Biochemistry, University of Utah School of Medicine, Salt Lake City, UT 84112, USA. Electronic address:

In this issue of Cell Metabolism, Herkenne et al. (2020) show that the mitochondrial fusion protein OPA1 promotes angiogenesis independent of its function in mitochondrial dynamics, identifying a key new therapeutic target to prevent vascular growth during development and tumor formation. Read More

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http://dx.doi.org/10.1016/j.cmet.2020.04.014DOI Listing

A Nutrient-Sensing Transition at Birth Triggers Glucose-Responsive Insulin Secretion.

Cell Metab 2020 May;31(5):1004-1016.e5

Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA 02138, USA; Howard Hughes Medical Institute, Cambridge, MA 02139, USA. Electronic address:

A drastic transition at birth, from constant maternal nutrient supply in utero to intermittent postnatal feeding, requires changes in the metabolic system of the neonate. Despite their central role in metabolic homeostasis, little is known about how pancreatic β cells adjust to the new nutritional challenge. Here, we find that after birth β cell function shifts from amino acid- to glucose-stimulated insulin secretion in correlation with the change in the nutritional environment. Read More

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http://dx.doi.org/10.1016/j.cmet.2020.04.004DOI Listing

Association of Blood Glucose Control and Outcomes in Patients with COVID-19 and Pre-existing Type 2 Diabetes.

Cell Metab 2020 06 1;31(6):1068-1077.e3. Epub 2020 May 1.

Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan 410013, China; Institute of Model Animal, Wuhan University, Wuhan 430072, China; Medical Science Research Center, Zhongnan Hospital of Wuhan University, Wuhan 430072, China; Basic Medical School, Wuhan University, Wuhan 430072, China. Electronic address:

Type 2 diabetes (T2D) is a major comorbidity of COVID-19. However, the impact of blood glucose (BG) control on the degree of required medical interventions and on mortality in patients with COVID-19 and T2D remains uncertain. Thus, we performed a retrospective, multi-centered study of 7,337 cases of COVID-19 in Hubei Province, China, among which 952 had pre-existing T2D. Read More

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http://dx.doi.org/10.1016/j.cmet.2020.04.021DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7252168PMC
June 2020
17.565 Impact Factor

Benefits of Metformin in Attenuating the Hallmarks of Aging.

Cell Metab 2020 Apr 23. Epub 2020 Apr 23.

Institute for Aging Research, Albert Einstein College of Medicine, Bronx, New York, NY, USA; Department of Medicine, Division of Endocrinology, Albert Einstein College of Medicine, Bronx, New York, NY, USA. Electronic address:

Biological aging involves an interplay of conserved and targetable molecular mechanisms, summarized as the hallmarks of aging. Metformin, a biguanide that combats age-related disorders and improves health span, is the first drug to be tested for its age-targeting effects in the large clinical trial-TAME (targeting aging by metformin). This review focuses on metformin's mechanisms in attenuating hallmarks of aging and their interconnectivity, by improving nutrient sensing, enhancing autophagy and intercellular communication, protecting against macromolecular damage, delaying stem cell aging, modulating mitochondrial function, regulating transcription, and lowering telomere attrition and senescence. Read More

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http://dx.doi.org/10.1016/j.cmet.2020.04.001DOI Listing
April 2020
17.565 Impact Factor

Deamidation Shunts RelA from Mediating Inflammation to Aerobic Glycolysis.

Cell Metab 2020 May 22;31(5):937-955.e7. Epub 2020 Apr 22.

Section of Infection and Immunity, Herman Ostrow School of Dentistry, Norris Comprehensive Cancer Center, University of Southern California, 925 W 34(th) Street, Los Angeles, CA 90089, USA. Electronic address:

Cell proliferation and inflammation are two metabolically demanding biological processes. How these competing processes are selectively executed in the same cell remains unknown. Here, we report that the enzyme carbamoyl-phosphate synthetase, aspartyl transcarbamoylase, and dihydroorotase (CAD) deamidates the RelA subunit of NF-κB in cancer cells to promote aerobic glycolysis and fuel cell proliferation in tumorigenesis. Read More

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http://dx.doi.org/10.1016/j.cmet.2020.04.006DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7257911PMC

Developmental and Tumor Angiogenesis Requires the Mitochondria-Shaping Protein Opa1.

Cell Metab 2020 May 20;31(5):987-1003.e8. Epub 2020 Apr 20.

Department of Biology, University of Padova, Via U. Bassi 58B, 35121 Padova, Italy; Veneto Institute of Molecular Medicine, Via Orus 2, 35129 Padova, Italy. Electronic address:

While endothelial cell (EC) function is influenced by mitochondrial metabolism, the role of mitochondrial dynamics in angiogenesis, the formation of new blood vessels from existing vasculature, is unknown. Here we show that the inner mitochondrial membrane mitochondrial fusion protein optic atrophy 1 (OPA1) is required for angiogenesis. In response to angiogenic stimuli, OPA1 levels rapidly increase to limit nuclear factor kappa-light-chain-enhancer of activated B cell (NFκB) signaling, ultimately allowing angiogenic genes expression and angiogenesis. Read More

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http://dx.doi.org/10.1016/j.cmet.2020.04.007DOI Listing

SGLT-2 Inhibitors and Regenerative Cell Exhaustion.

Cell Metab 2020 May 16;31(5):884-885. Epub 2020 Apr 16.

Division of Cardiac Surgery, Keenan Research Centre for Biomedical Science of St. Michael's Hospital, Toronto, ON, Canada; Insitute of Medical Sciences, University of Toronto, Toronto, ON, Canada; Department of Surgery, University of Toronto, Toronto, ON, Canada; Department of Pharmacology and Toxicology, University of Toronto, Toronto, ON, Canada. Electronic address:

In response to the Letter by Fadini, Hess et al. discuss the interpretation of their data and the details of the multiparametric analyses employed to measure the changes in circulating provascular cell content in patients with type 2 diabetes receiving empagliflozin compared to placebo treatment. Read More

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http://dx.doi.org/10.1016/j.cmet.2020.04.003DOI Listing

Patch-Seq Links Single-Cell Transcriptomes to Human Islet Dysfunction in Diabetes.

Cell Metab 2020 May 16;31(5):1017-1031.e4. Epub 2020 Apr 16.

Department of Pharmacology, University of Alberta, Edmonton, AB T6G 2E1, Canada; Alberta Diabetes Institute, University of Alberta, Edmonton, AB T6G 2E1, Canada. Electronic address:

Impaired function of pancreatic islet cells is a major cause of metabolic dysregulation and disease in humans. Despite this, it remains challenging to directly link physiological dysfunction in islet cells to precise changes in gene expression. Here we show that single-cell RNA sequencing combined with electrophysiological measurements of exocytosis and channel activity (patch-seq) can be used to link endocrine physiology and transcriptomes at the single-cell level. Read More

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http://dx.doi.org/10.1016/j.cmet.2020.04.005DOI Listing

SGLT-2 Inhibitors and Circulating Progenitor Cells in Diabetes.

Cell Metab 2020 May 16;31(5):883. Epub 2020 Apr 16.

Department of Medicine, University of Padova, Via Giustiniani 2, 35128 Padova, Italy. Electronic address:

Hess et al. recently hypothesized that shifts in circulating progenitor cell populations may drive cardiovascular protection by SGLT-2 inhibitors in patients with type 2 diabetes. In this Letter, Fadini challenges that interpretation and discusses previous findings from an independent randomized placebo-controlled trial indicating that cardiovascular protection by SGLT-2 inhibitors may not directly involve circulating stem/progenitor cells. Read More

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http://dx.doi.org/10.1016/j.cmet.2020.04.002DOI Listing

Pimozide Alleviates Hyperglycemia in Diet-Induced Obesity by Inhibiting Skeletal Muscle Ketone Oxidation.

Cell Metab 2020 May 9;31(5):909-919.e8. Epub 2020 Apr 9.

Faculty of Pharmacy and Pharmaceutical Sciences, University of Alberta, Edmonton, AB, Canada; Alberta Diabetes Institute, University of Alberta, Edmonton, AB, Canada; Cardiovascular Research Centre, University of Alberta, Edmonton, AB, Canada. Electronic address:

Perturbations in carbohydrate, lipid, and protein metabolism contribute to obesity-induced type 2 diabetes (T2D), though whether alterations in ketone body metabolism influence T2D pathology is unknown. We report here that activity of the rate-limiting enzyme for ketone body oxidation, succinyl-CoA:3-ketoacid-CoA transferase (SCOT/Oxct1), is increased in muscles of obese mice. We also found that the diphenylbutylpiperidine pimozide, which is approved to suppress tics in individuals with Tourette syndrome, is a SCOT antagonist. Read More

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http://dx.doi.org/10.1016/j.cmet.2020.03.017DOI Listing