2,697 results match your criteria Cell Metabolism [Journal]


Time of Exercise Specifies the Impact on Muscle Metabolic Pathways and Systemic Energy Homeostasis.

Cell Metab 2019 Apr 12. Epub 2019 Apr 12.

Center for Epigenetics and Metabolism, INSERM U1233, Department of Biological Chemistry, School of Medicine, University of California, Irvine, Irvine, CA, USA. Electronic address:

While the timing of food intake is important, it is unclear whether the effects of exercise on energy metabolism are restricted to unique time windows. As circadian regulation is key to controlling metabolism, understanding the impact of exercise performed at different times of the day is relevant for physiology and homeostasis. Using high-throughput transcriptomic and metabolomic approaches, we identify distinct responses of metabolic oscillations that characterize exercise in either the early rest phase or the early active phase in mice. Read More

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http://dx.doi.org/10.1016/j.cmet.2019.03.013DOI Listing

Pyruvate-Carboxylase-Mediated Anaplerosis Promotes Antioxidant Capacity by Sustaining TCA Cycle and Redox Metabolism in Liver.

Cell Metab 2019 Apr 16. Epub 2019 Apr 16.

Center for Human Nutrition, The University of Texas Southwestern Medical Center, Dallas, TX, USA; Department of Pharmacology, The University of Texas Southwestern Medical Center, Dallas, TX, USA. Electronic address:

The hepatic TCA cycle supports oxidative and biosynthetic metabolism. This dual responsibility requires anaplerotic pathways, such as pyruvate carboxylase (PC), to generate TCA cycle intermediates necessary for biosynthesis without disrupting oxidative metabolism. Liver-specific PC knockout (LPCKO) mice were created to test the role of anaplerotic flux in liver metabolism. Read More

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https://linkinghub.elsevier.com/retrieve/pii/S15504131193018
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http://dx.doi.org/10.1016/j.cmet.2019.03.014DOI Listing
April 2019
8 Reads

Physiological and Molecular Dissection of Daily Variance in Exercise Capacity.

Cell Metab 2019 Apr 11. Epub 2019 Apr 11.

Department of Biomolecular Sciences, Weizmann Institute of Science, 7610001 Rehovot, Israel. Electronic address:

Physical performance relies on the concerted action of myriad responses, many of which are under circadian clock control. Little is known, however, regarding the time-dependent effect on exercise performance at the molecular level. We found that both mice and humans exhibit daytime variance in exercise capacity between the early and late part of their active phase. Read More

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http://dx.doi.org/10.1016/j.cmet.2019.03.012DOI Listing
April 2019
1 Read

Choline Uptake and Metabolism Modulate Macrophage IL-1β and IL-18 Production.

Cell Metab 2019 Apr 8. Epub 2019 Apr 8.

Departments of Pharmacology and Pathology, University of California San Diego, La Jolla, CA, 92037, USA. Electronic address:

Choline is a vitamin-like nutrient that is taken up via specific transporters and metabolized by choline kinase, which converts it to phosphocholine needed for de novo synthesis of phosphatidylcholine (PC), the main phospholipid of cellular membranes. We found that Toll-like receptor (TLR) activation enhances choline uptake by macrophages and microglia through induction of the choline transporter CTL1. Inhibition of CTL1 expression or choline phosphorylation attenuated NLRP3 inflammasome activation and IL-1β and IL-18 production in stimulated macrophages. Read More

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https://linkinghub.elsevier.com/retrieve/pii/S15504131193013
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http://dx.doi.org/10.1016/j.cmet.2019.03.011DOI Listing
April 2019
8 Reads
17.565 Impact Factor

Epigenetics in Human Obesity and Type 2 Diabetes.

Cell Metab 2019 Apr 9. Epub 2019 Apr 9.

Epigenetics and Diabetes Unit, Department of Clinical Sciences Malmö, Lund University Diabetes Centre, Scania University Hospital, Malmö, Sweden.

Epigenetic mechanisms control gene activity and the development of an organism. The epigenome includes DNA methylation, histone modifications, and RNA-mediated processes, and disruption of this balance may cause several pathologies and contribute to obesity and type 2 diabetes (T2D). This Review summarizes epigenetic signatures obtained from human tissues of relevance for metabolism-i. Read More

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https://linkinghub.elsevier.com/retrieve/pii/S15504131193013
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http://dx.doi.org/10.1016/j.cmet.2019.03.009DOI Listing
April 2019
3 Reads

Insulin-Driven PI3K-AKT Signaling in the Hepatocyte Is Mediated by Redundant PI3Kα and PI3Kβ Activities and Is Promoted by RAS.

Cell Metab 2019 Apr 3. Epub 2019 Apr 3.

The Wallenberg Laboratory and Sahlgrenska Center for Cardiovascular and Metabolic Research, Department of Molecular and Clinical Medicine, Institute of Medicine, University of Gothenburg, Gothenburg, Sweden. Electronic address:

Phosphatidylinositol-3-kinase (PI3K) activity is aberrant in tumors, and PI3K inhibitors are investigated as cancer therapeutics. PI3K signaling mediates insulin action in metabolism, but the role of PI3K isoforms in insulin signaling remains unresolved. Defining the role of PI3K isoforms in insulin signaling is necessary for a mechanistic understanding of insulin action and to develop PI3K inhibitors with optimal therapeutic index. Read More

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http://dx.doi.org/10.1016/j.cmet.2019.03.010DOI Listing

Transmembrane 4 L Six Family Member 5 Senses Arginine for mTORC1 Signaling.

Cell Metab 2019 Apr 1. Epub 2019 Apr 1.

Interdisciplinary Program in Genetic Engineering, Seoul National University, Seoul 08826, South Korea; Department of Pharmacy, Research Institute of Pharmaceutical Sciences, College of Pharmacy, Seoul National University, Seoul 08826, South Korea. Electronic address:

The mechanistic target of rapamycin complex (mTORC1) is a signaling hub on the lysosome surface, responding to lysosomal amino acids. Although arginine is metabolically important, the physiological arginine sensor that activates mTOR remains unclear. Here, we show that transmembrane 4 L six family member 5 (TM4SF5) translocates from plasma membrane to lysosome upon arginine sufficiency and senses arginine, culminating in mTORC1/S6K1 activation. Read More

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http://dx.doi.org/10.1016/j.cmet.2019.03.005DOI Listing
April 2019
17.565 Impact Factor

Watch What You (Self-) Eat: Autophagic Mechanisms that Modulate Metabolism.

Cell Metab 2019 Apr;29(4):803-826

Life Sciences Institute, University of Michigan, Ann Arbor, MI 48109, USA; Department of Molecular, Cellular and Developmental Biology, University of Michigan, Ann Arbor, MI 48109, USA. Electronic address:

Autophagy is an evolutionarily conserved lysosome- or vacuole-dependent catabolic pathway in eukaryotes. Autophagy functions basally for cellular quality control and is induced to act as an alternative source of basic metabolites during nutrient deprivation. These functions of autophagy are intimately connected to the regulation of metabolism, and the metabolic status of the cell in turn controls the nature and extent of autophagic induction. Read More

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http://dx.doi.org/10.1016/j.cmet.2019.03.003DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6450419PMC

Vascular Organoids: Are We Entering a New Area of Cardiometabolic Research?

Cell Metab 2019 Apr;29(4):792-794

Division of Cardiac Surgery, St Michael's Hospital, Toronto, ON, Canada; Department of Pharmacology and Toxicology, University of Toronto, Toronto, ON, Canada; Institute of Medical Science, University of Toronto, Toronto, ON, Canada; Department of Surgery, University of Toronto, Toronto, ON, Canada.

Recently in Nature, Wimmer et al. (2019) reported on the development of a human organoid model of vascular development recapitulating vascular pathology during type 2 diabetes. Integration of these organoids into the vasculature of immunodeficient mice may provide cardiometabolic researchers with a "personalized" platform for novel therapeutic discovery. Read More

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http://dx.doi.org/10.1016/j.cmet.2019.03.008DOI Listing

Fatty Acid Desaturation Gets a NAD Reputation.

Cell Metab 2019 Apr;29(4):790-792

Division of Geriatrics and Nutritional Sciences, Center for Human Nutrition, Department of Medicine, Washington University School of Medicine, St. Louis, MO, USA. Electronic address:

delta-5 desaturase and delta-6 desaturase are enzymes known to be involved in the synthesis of highly unsaturated fatty acids. In this issue, Kim et al. (2019) show that production of NAD by this desaturase reaction is an adaptive response to NAD depletion that may regulate cellular REDOX status. Read More

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http://dx.doi.org/10.1016/j.cmet.2019.03.007DOI Listing
April 2019
1 Read

Gut T Cells Feast on GLP-1 to Modulate Cardiometabolic Disease.

Cell Metab 2019 Apr;29(4):787-789

Division of Cellular & Molecular Biology, Diabetes Research Group, Toronto General Hospital Research Institute (TGHRI), University Health Network, Toronto, ON M5G 1L7, Canada; Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON M5S 1A8, Canada; Department of Immunology, University of Toronto, Toronto, ON M5S 1A8, Canada; Department of Pathology, University Health Network, Toronto, ON M5G 2C4, Canada; Buck Institute for Research on Aging, 8001 Redwood Boulevard, Novato, CA 94945, USA. Electronic address:

Glucagon-like peptide-1 (GLP-1) is an enteroendocrine hormone that controls insulin secretion, intestinal function, and food intake. Recently in Nature, He et al. (2019) reported that gut intraepithelial T cells regulate GLP-1 bioavailability by capturing it on GLP-1 receptors and impacting L-cell numbers. Read More

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https://linkinghub.elsevier.com/retrieve/pii/S15504131193013
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http://dx.doi.org/10.1016/j.cmet.2019.03.002DOI Listing
April 2019
7 Reads

Metabolic Adaptation Fuels Lymph Node Metastasis.

Cell Metab 2019 Apr;29(4):785-786

Children's Research Institute and Department of Pediatrics, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA; Howard Hughes Medical Institute, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA. Electronic address:

Many cancers metastasize regionally through lymphatics before metastasizing systemically through blood vessels. However, metastasis through blood has been studied much more extensively than metastasis through lymph. Recently in Science, Lee et al. Read More

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http://dx.doi.org/10.1016/j.cmet.2019.03.006DOI Listing
April 2019
1 Read

Membrane Cholesterol Efflux Drives Tumor-Associated Macrophage Reprogramming and Tumor Progression.

Cell Metab 2019 Mar 21. Epub 2019 Mar 21.

CNRS, Aix Marseille University, INSERM, CIML, Marseille 13009, France; Centre for Inflammation Biology and Cancer Immunology, School of Immunology & Micriboal Sciences, King's College London, London SE1 1UL, UK; Henan Key Laboratory of Immunology and Targeted Therapy, School of Laboratory Medicine, Xinxiang Medical University, Xinxiang 453003, Henan Province, China. Electronic address:

Macrophages possess intrinsic tumoricidal activity, yet tumor-associated macrophages (TAMs) rapidly adopt an alternative phenotype within the tumor microenvironment that is marked by tumor-promoting immunosuppressive and trophic functions. The mechanisms that promote such TAM polarization remain poorly understood, but once identified, they may represent important therapeutic targets to block the tumor-promoting functions of TAMs and restore their anti-tumor potential. Here, we have characterized TAMs in a mouse model of metastatic ovarian cancer. Read More

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http://dx.doi.org/10.1016/j.cmet.2019.02.016DOI Listing

Metabolic Reprogramming in Astrocytes Distinguishes Region-Specific Neuronal Susceptibility in Huntington Mice.

Cell Metab 2019 Mar 26. Epub 2019 Mar 26.

Division of Molecular Biophysics and Integrated Bioimaging, Lawrence Berkeley National Laboratory, Berkeley, CA 94720, USA. Electronic address:

The basis for region-specific neuronal toxicity in Huntington disease is unknown. Here, we show that region-specific neuronal vulnerability is a substrate-driven response in astrocytes. Glucose is low in HdhQ(150/150) animals, and astrocytes in each brain region adapt by metabolically reprogramming their mitochondria to use endogenous, non-glycolytic metabolites as an alternative fuel. Read More

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http://dx.doi.org/10.1016/j.cmet.2019.03.004DOI Listing
March 2019
1 Read

Telomere Dysfunction Induces Sirtuin Repression that Drives Telomere-Dependent Disease.

Cell Metab 2019 Mar 20. Epub 2019 Mar 20.

Department of Physiology and Biophysics, Baylor College of Medicine, Houston, TX 77030, USA; Huffington Center on Aging, Baylor College of Medicine, Houston, TX 77030, USA. Electronic address:

Telomere shortening is associated with stem cell decline, fibrotic disorders, and premature aging through mechanisms that are incompletely understood. Here, we show that telomere shortening in livers of telomerase knockout mice leads to a p53-dependent repression of all seven sirtuins. P53 regulates non-mitochondrial sirtuins (Sirt1, 2, 6, and 7) post-transcriptionally through microRNAs (miR-34a, 26a, and 145), while the mitochondrial sirtuins (Sirt3, 4, and 5) are regulated in a peroxisome proliferator-activated receptor gamma co-activator 1 alpha-/beta-dependent manner at the transcriptional level. Read More

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http://dx.doi.org/10.1016/j.cmet.2019.03.001DOI Listing
March 2019
1 Read
17.565 Impact Factor

Increased Serine Synthesis Provides an Advantage for Tumors Arising in Tissues Where Serine Levels Are Limiting.

Cell Metab 2019 Mar 13. Epub 2019 Mar 13.

Koch Institute for Integrative Cancer Research, Cambridge, MA, USA; Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Dana-Farber Cancer Institute, Boston, MA 02215, USA; Broad Institute, Cambridge, MA 02139, USA. Electronic address:

Tumors exhibit altered metabolism compared to normal tissues. Many cancers upregulate expression of serine synthesis pathway enzymes, and some tumors exhibit copy-number gain of the gene encoding the first enzyme in the pathway, phosphoglycerate dehydrogenase (PHGDH). However, whether increased serine synthesis promotes tumor growth and how serine synthesis benefits tumors is controversial. Read More

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https://linkinghub.elsevier.com/retrieve/pii/S15504131193012
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http://dx.doi.org/10.1016/j.cmet.2019.02.015DOI Listing
March 2019
5 Reads

Mitochondria Bound to Lipid Droplets: Where Mitochondrial Dynamics Regulate Lipid Storage and Utilization.

Cell Metab 2019 Apr 21;29(4):827-835. Epub 2019 Mar 21.

Division of Endocrinology, Department of Medicine, and Department of Molecular and Medical Pharmacology, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA; Obesity Research Center, Department of Medicine, Boston University School of Medicine, Boston, MA, USA. Electronic address:

The isolation and biochemical characterization of lipid droplet (LD)-associated mitochondria revealed the capacity of the cell to produce and maintain distinct mitochondrial populations carrying disparate proteome and dissimilar capacities to oxidize fatty acids and pyruvate. With mitochondrial motility being a central parameter determining mitochondrial fusion, adherence to LDs provides a mechanism by which peridroplet mitochondria (PDM) remain segregated from cytoplasmic mitochondria (CM). The existence of metabolically distinct subpopulations provides an explanation for the capacity of mitochondria within the individual cell to be involved simultaneously in fatty acid oxidation and LD formation. Read More

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https://linkinghub.elsevier.com/retrieve/pii/S15504131193007
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http://dx.doi.org/10.1016/j.cmet.2019.02.011DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6476311PMC
April 2019
9 Reads

Dietary Restriction Extends Lifespan through Metabolic Regulation of Innate Immunity.

Cell Metab 2019 Mar 21. Epub 2019 Mar 21.

Research Division, Joslin Diabetes Center, Boston, MA 02215, USA; Department of Genetics, Harvard Medical School, Boston, MA 02115, USA; Harvard Stem Cell Institute, Cambridge, MA 02138, USA. Electronic address:

Chronic inflammation predisposes to aging-associated disease, but it is unknown whether immunity regulation might be important for extending healthy lifespan. Here we show that in C. elegans, dietary restriction (DR) extends lifespan by modulating a conserved innate immunity pathway that is regulated by p38 signaling and the transcription factor ATF-7. Read More

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https://linkinghub.elsevier.com/retrieve/pii/S15504131193010
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http://dx.doi.org/10.1016/j.cmet.2019.02.013DOI Listing
March 2019
4 Reads

Phosphoproteomics Reveals the GSK3-PDX1 Axis as a Key Pathogenic Signaling Node in Diabetic Islets.

Cell Metab 2019 Mar 7. Epub 2019 Mar 7.

Proteomics and Signal Transduction, Max-Planck Institute of Biochemistry, 82152 Martinsried, Germany. Electronic address:

Progressive decline of pancreatic beta cell function is central to the pathogenesis of type 2 diabetes. Protein phosphorylation regulates glucose-stimulated insulin secretion from beta cells, but how signaling networks are remodeled in diabetic islets in vivo remains unknown. Using high-sensitivity mass spectrometry-based proteomics, we quantified 6,500 proteins and 13,000 phosphopeptides in islets of obese diabetic mice and matched controls, revealing drastic remodeling of key kinase hubs and signaling pathways. Read More

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http://dx.doi.org/10.1016/j.cmet.2019.02.012DOI Listing
March 2019
1 Read

Case Reports of Pre-clinical Replication Studies in Metabolism and Diabetes.

Cell Metab 2019 Apr 14;29(4):795-802. Epub 2019 Mar 14.

Novo Nordisk A/S, Måløv, Denmark.

Recent articles have highlighted the lack of reproducibility of data from scientific publications. Here we would argue that a better way to describe and also tackle this matter is to use the term "lack of robustness," since it points toward potential solutions. Presenting several case reports, we highlight examples with common underlying issues from Novo Nordisk's experience: animal model variability, reagent quality, and inter-lab variability. Read More

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http://dx.doi.org/10.1016/j.cmet.2019.02.004DOI Listing

High Glucose Triggers Nucleotide Imbalance through O-GlcNAcylation of Key Enzymes and Induces KRAS Mutation in Pancreatic Cells.

Cell Metab 2019 Mar 4. Epub 2019 Mar 4.

Genomics Research Center, Academia Sinica, Taipei 11529, Taiwan; Drug Development Center, China Medical University, Taichung 40402, Taiwan. Electronic address:

KRAS mutations are the earliest events found in approximately 90% of pancreatic ductal adenocarcinomas (PDACs). However, little is known as to why KRAS mutations preferentially occur in PDACs and what processes/factors generate these mutations. While abnormal carbohydrate metabolism is associated with a high risk of pancreatic cancer, it remains elusive whether a direct relationship between KRAS mutations and sugar metabolism exists. Read More

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http://dx.doi.org/10.1016/j.cmet.2019.02.005DOI Listing
March 2019
1 Read

LINE1 Derepression in Aged Wild-Type and SIRT6-Deficient Mice Drives Inflammation.

Cell Metab 2019 Apr 7;29(4):871-885.e5. Epub 2019 Mar 7.

Department of Biology, University of Rochester, Rochester, NY 14627, USA. Electronic address:

Mice deficient for SIRT6 exhibit a severely shortened lifespan, growth retardation, and highly elevated LINE1 (L1) activity. Here we report that SIRT6-deficient cells and tissues accumulate abundant cytoplasmic L1 cDNA, which triggers strong type I interferon response via activation of cGAS. Remarkably, nucleoside reverse-transcriptase inhibitors (NRTIs), which inhibit L1 retrotransposition, significantly improved health and lifespan of SIRT6 knockout mice and completely rescued type I interferon response. Read More

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http://dx.doi.org/10.1016/j.cmet.2019.02.014DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6449196PMC
April 2019
2 Reads

Improving Drug Discovery by Nucleic Acid Delivery in Engineered Human Microlivers.

Cell Metab 2019 Mar;29(3):727-735.e3

Institute for Medical Engineering and Science, Massachusetts Institute of Technology, Cambridge, MA 02142, USA; Broad Institute, Cambridge, MA 02142, USA; Howard Hughes Medical Institute, Chevy Chase, MD 20815, USA; Koch Institute for Integrative Cancer Research, Cambridge, MA 02142, USA; Department of Medicine, Brigham and Women's Hospital, Boston, MA 02115, USA. Electronic address:

The liver plays a central role in metabolism; however, xenobiotic metabolism variations between human hepatocytes and those in model organisms create challenges in establishing functional test beds to detect the potential drug toxicity and efficacy of candidate small molecules. In the emerging areas of RNA interference, viral gene therapy, and genome editing, more robust, long-lasting, and predictive human liver models may accelerate progress. Here, we apply a new modality to a previously established, functionally stable, multi-well bioengineered microliver-fabricated from primary human hepatocytes and supportive stromal cells-in order to advance both small molecule and nucleic acid therapeutic pipelines. Read More

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https://linkinghub.elsevier.com/retrieve/pii/S15504131193006
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http://dx.doi.org/10.1016/j.cmet.2019.02.003DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6408324PMC
March 2019
5 Reads

Caloric Restriction Mimetics against Age-Associated Disease: Targets, Mechanisms, and Therapeutic Potential.

Cell Metab 2019 Mar;29(3):592-610

Equipe 11 labellisée Ligue contre le Cancer, Centre de Recherche des Cordeliers, INSERM U 1138, Paris, France; Metabolomics and Cell Biology Platforms, Gustave Roussy Comprehensive Cancer Center, Villejuif, France; Université Paris Descartes, Sorbonne Paris Cité, Paris, France; Université Pierre et Marie Curie, Paris, France; Pôle de Biologie, Hôpital Européen Georges Pompidou, Paris, France; Karolinska Institute, Department of Women's and Children's Health, Karolinska University Hospital, Stockholm, Sweden; Center of Systems Medicine, Chinese Academy of Science, Suzhou, China. Electronic address:

The increase in life expectancy has boosted the incidence of age-related pathologies beyond social and economic sustainability. Consequently, there is an urgent need for interventions that revert or at least prevent the pathogenic age-associated deterioration. The permanent or periodic reduction of calorie intake without malnutrition (caloric restriction and fasting) is the only strategy that reliably extends healthspan in mammals including non-human primates. Read More

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http://dx.doi.org/10.1016/j.cmet.2019.01.018DOI Listing

Navigating Two Roads to Glucose Normalization in Diabetes: Automated Insulin Delivery Devices and Cell Therapy.

Cell Metab 2019 Mar;29(3):545-563

Departments of Cellular and Physiological Sciences, and Surgery, Life Sciences Institute, School of Biomedical Engineering, University of British Columbia, Vancouver, BC V6T 1Z3, Canada. Electronic address:

Incredible strides have been made since the discovery of insulin almost 100 years ago. Insulin formulations have improved dramatically, glucose levels can be measured continuously, and recently first-generation biomechanical "artificial pancreas" systems have been approved by regulators around the globe. However, still only a small fraction of patients with diabetes achieve glycemic goals. Read More

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http://dx.doi.org/10.1016/j.cmet.2019.02.007DOI Listing
March 2019
4 Reads

"Deepening" Insight on Skin Aging and Anti-microbial Immunity.

Cell Metab 2019 Mar;29(3):515-517

Cutaneous Leukocyte Biology Section, Dermatology Branch, NIAMS, NIH, Bethesda, MD 20892, USA. Electronic address:

Skin aging is of considerable interest from various perspectives, ranging from aesthetics to cancer development. Zhang et al. (2019) elucidate an immunological consequence of aging in the adipose layer of skin. Read More

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http://dx.doi.org/10.1016/j.cmet.2019.02.006DOI Listing

A New Transkingdom Dimension to NO Signaling.

Cell Metab 2019 Mar;29(3):513-515

Institut de Génomique Fonctionnelle de Lyon, Université de Lyon, Ecole Normale Supérieure de Lyon, CNRS UMR5242, UCBL1, Lyon, France. Electronic address:

Bacterial-derived metabolites profoundly influence the host's cellular and organismal physiology. Seth et al. (2019) report that via interspecies S-nitrosylation, microbiota-derived nitric oxide directly alters the host's Argonaute family protein activity, and consequently impinges on the overall post-transcriptional gene silencing program through the microRNA (miRNA) machinery. Read More

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http://dx.doi.org/10.1016/j.cmet.2019.02.008DOI Listing
March 2019
1 Read

Bioengineering and Metabolism Voices.

Authors:

Cell Metab 2019 Mar;29(3):506-512

To explore the world where technology fuses with the life sciences, we asked a diverse group of scientists to tell us about bioengineering innovations that impact metabolism and physiology. From miniaturized models of physiological systems to smart drugs with feedback control, we take a journey with them through the frontiers of biomedicine. Read More

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http://dx.doi.org/10.1016/j.cmet.2019.02.009DOI Listing

Editorial: Bioengineering and Metabolism.

Cell Metab 2019 Mar;29(3):505

Editor-in-Chief, Cell Metabolism.

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http://dx.doi.org/10.1016/j.cmet.2019.02.010DOI Listing
March 2019
5 Reads

Transcriptional Basis for Rhythmic Control of Hunger and Metabolism within the AgRP Neuron.

Cell Metab 2019 Feb 18. Epub 2019 Feb 18.

Department of Medicine, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA. Electronic address:

The alignment of fasting and feeding with the sleep/wake cycle is coordinated by hypothalamic neurons, though the underlying molecular programs remain incompletely understood. Here, we demonstrate that the clock transcription pathway maximizes eating during wakefulness and glucose production during sleep through autonomous circadian regulation of NPY/AgRP neurons. Tandem profiling of whole-cell and ribosome-bound mRNAs in morning and evening under dynamic fasting and fed conditions identified temporal control of activity-dependent gene repertoires in AgRP neurons central to synaptogenesis, bioenergetics, and neurotransmitter and peptidergic signaling. Read More

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https://linkinghub.elsevier.com/retrieve/pii/S15504131193006
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http://dx.doi.org/10.1016/j.cmet.2019.01.023DOI Listing
February 2019
21 Reads
17.565 Impact Factor

Macrophage-Released Pyrimidines Inhibit Gemcitabine Therapy in Pancreatic Cancer.

Cell Metab 2019 Feb 21. Epub 2019 Feb 21.

Department of Molecular and Integrative Physiology, University of Michigan, Ann Arbor, MI 48109, USA; University of Michigan Rogel Cancer Center, University of Michigan, Ann Arbor, MI 48109, USA; Department of Internal Medicine, Division of Gastroenterology and Hepatology, University of Michigan, Ann Arbor, MI 48109, USA. Electronic address:

Pancreatic ductal adenocarcinoma (PDA) is characterized by abundant infiltration of tumor-associated macrophages (TAMs). TAMs have been reported to drive resistance to gemcitabine, a frontline chemotherapy in PDA, though the mechanism of this resistance remains unclear. Profiling metabolite exchange, we demonstrate that macrophages programmed by PDA cells release a spectrum of pyrimidine species. Read More

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http://dx.doi.org/10.1016/j.cmet.2019.02.001DOI Listing
February 2019
6 Reads

Differential Metabolic Reprogramming by Zika Virus Promotes Cell Death in Human versus Mosquito Cells.

Cell Metab 2019 Feb 16. Epub 2019 Feb 16.

Department of Biological Chemistry, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA; Department of Molecular and Medical Pharmacology, 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; UCLA Jonsson Comprehensive Cancer Center, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA. Electronic address:

Zika virus is a pathogen that poses serious consequences, including congenital microcephaly. Although many viruses reprogram host cell metabolism, whether Zika virus alters cellular metabolism and the functional consequences of Zika-induced metabolic changes remain unknown. Here, we show that Zika virus infection differentially reprograms glucose metabolism in human versus C6/36 mosquito cells by increasing glucose use in the tricarboxylic acid cycle in human cells versus increasing glucose use in the pentose phosphate pathway in mosquito cells. Read More

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http://dx.doi.org/10.1016/j.cmet.2019.01.024DOI Listing
February 2019

Targeted Elimination of Senescent Beta Cells Prevents Type 1 Diabetes.

Cell Metab 2019 Feb 14. Epub 2019 Feb 14.

Diabetes Center, University of California, San Francisco, San Francisco, CA 94143, USA. Electronic address:

Type 1 diabetes (T1D) is an organ-specific autoimmune disease characterized by hyperglycemia due to progressive loss of pancreatic beta cells. Immune-mediated beta cell destruction drives the disease, but whether beta cells actively participate in the pathogenesis remains unclear. Here, we show that during the natural history of T1D in humans and the non-obese diabetic (NOD) mouse model, a subset of beta cells acquires a senescence-associated secretory phenotype (SASP). Read More

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http://dx.doi.org/10.1016/j.cmet.2019.01.021DOI Listing
February 2019

Mitochondrial Dysfunction in C. elegans Activates Mitochondrial Relocalization and Nuclear Hormone Receptor-Dependent Detoxification Genes.

Cell Metab 2019 Feb 14. Epub 2019 Feb 14.

Department of Molecular Biology, Massachusetts General Hospital, Boston, MA 02114, USA; Department of Genetics, Harvard Medical School, Boston, MA 02115, USA. Electronic address:

In Caenorhabditis elegans, mitochondrial dysfunction caused by mutation or toxins activates programs of detoxification and immune response. A genetic screen for mutations that constitutively induce C. elegans mitochondrial defense revealed reduction-of-function mutations in the mitochondrial chaperone hsp-6/mtHSP70 and gain-of-function mutations in the Mediator component mdt-15/MED15. Read More

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http://dx.doi.org/10.1016/j.cmet.2019.01.022DOI Listing
February 2019
1 Read

Deubiquitinases Maintain Protein Homeostasis and Survival of Cancer Cells upon Glutathione Depletion.

Cell Metab 2019 Feb 13. Epub 2019 Feb 13.

Ludwig Cancer Center, Boston, MA 02115, USA; Harvard Medical School, Boston, MA 02115, USA. Electronic address:

Cells are subjected to oxidative stress during the initiation and progression of tumors, and this imposes selective pressure for cancer cells to adapt mechanisms to tolerate these conditions. Here, we examined the dependency of cancer cells on glutathione (GSH), the most abundant cellular antioxidant. While cancer cell lines displayed a broad range of sensitivities to inhibition of GSH synthesis, the majority were resistant to GSH depletion. Read More

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http://dx.doi.org/10.1016/j.cmet.2019.01.020DOI Listing
February 2019
1 Read

Glutamine Metabolism Regulates Proliferation and Lineage Allocation in Skeletal Stem Cells.

Cell Metab 2019 Apr 14;29(4):966-978.e4. Epub 2019 Feb 14.

Department of Orthopaedic Surgery, Duke Orthopaedic Cellular, Developmental, and Genome Laboratories, Duke University School of Medicine, Durham, NC 27710, USA; Department of Cell Biology, Duke University, Durham, NC 27710, USA. Electronic address:

Skeletal stem cells (SSCs) are postulated to provide a continuous supply of osteoblasts throughout life. However, under certain conditions, the SSC population can become incorrectly specified or is not maintained, resulting in reduced osteoblast formation, decreased bone mass, and in severe cases, osteoporosis. Glutamine metabolism has emerged as a critical regulator of many cellular processes in diverse pathologies. Read More

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http://dx.doi.org/10.1016/j.cmet.2019.01.016DOI Listing

Cancer Metabolism Drives a Stromal Regenerative Response.

Cell Metab 2019 Mar 14;29(3):576-591. Epub 2019 Feb 14.

Memorial Sloan Kettering Cancer Center, Cancer Biology and Genetics Program, New York, NY 10065, USA. Electronic address:

The metabolic reprogramming associated with malignant transformation has led to a growing appreciation of the nutrients required to support anabolic cell growth. Less well studied is how cancer cells satisfy those demands in vivo, where they are dispersed within a complex microenvironment. Tumor-associated stromal components can support tumor growth by providing nutrients that supplement those provided by the local vasculature. Read More

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http://dx.doi.org/10.1016/j.cmet.2019.01.015DOI Listing
March 2019
5 Reads

Oxygen and Carbon Dioxide Rhythms Are Circadian Clock Controlled and Differentially Directed by Behavioral Signals.

Cell Metab 2019 Feb 11. Epub 2019 Feb 11.

Department of Biomolecular Sciences, Weizmann Institute of Science, Rehovot 7610001, Israel. Electronic address:

Daily rhythms in animal physiology are driven by endogenous circadian clocks in part through rest-activity and feeding-fasting cycles. Here, we examined principles that govern daily respiration. We monitored oxygen consumption and carbon dioxide release, as well as tissue oxygenation in freely moving animals to specifically dissect the role of circadian clocks and feeding time on daily respiration. Read More

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http://dx.doi.org/10.1016/j.cmet.2019.01.007DOI Listing
February 2019
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A Long-Acting PYY Analog Mediates Robust Anorectic Efficacy with Minimal Emesis in Nonhuman Primates.

Cell Metab 2019 Apr 14;29(4):837-843.e5. Epub 2019 Feb 14.

Discovery Biology, Cardiovascular and Metabolic Therapeutic Areas, Janssen Research and Development, Spring House, PA, USA. Electronic address:

The gut hormone PYY reduces food intake in humans and exhibits at least additive efficacy in combination with GLP-1. However, the utility of PYY analogs as anti-obesity agents has been severely limited by emesis and rapid proteolysis, a profile similarly observed with native PYY in obese rhesus macaques. Here, we found that antibody conjugation of a cyclized PYY analog achieved high NPY2R selectivity, unprecedented in vivo stability, and gradual infusion-like exposure. Read More

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https://linkinghub.elsevier.com/retrieve/pii/S15504131193001
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http://dx.doi.org/10.1016/j.cmet.2019.01.017DOI Listing
April 2019
9 Reads
17.565 Impact Factor

Serine Metabolism Supports Macrophage IL-1β Production.

Cell Metab 2019 Apr 14;29(4):1003-1011.e4. Epub 2019 Feb 14.

Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA. Electronic address:

Serine is a substrate for nucleotide, NADPH, and glutathione (GSH) synthesis. Previous studies in cancer cells and lymphocytes have shown that serine-dependent one-carbon units are necessary for nucleotide production to support proliferation. Presently, it is unknown whether serine metabolism impacts the function of non-proliferative cells, such as inflammatory macrophages. Read More

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http://dx.doi.org/10.1016/j.cmet.2019.01.014DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6447453PMC
April 2019
15 Reads

Systematic Dissection of the Metabolic-Apoptotic Interface in AML Reveals Heme Biosynthesis to Be a Regulator of Drug Sensitivity.

Cell Metab 2019 Feb 5. Epub 2019 Feb 5.

Department of Pharmacology & Cancer Biology, Duke University School of Medicine, Durham, NC, USA. Electronic address:

Crosstalk between metabolic and survival pathways is critical for cellular homeostasis, but the connectivity between these processes remains poorly defined. We used loss-of-function CRISPR/Cas9 knockout screening to identify metabolic genes capable of influencing cellular commitment to apoptosis, using sensitization to the BCL-2 inhibitor ABT-199 in BCL-2-dependent acute myeloid leukemia (AML) cell lines as a proxy for apoptotic disposition. This analysis revealed metabolic pathways that specifically cooperate with BCL-2 to sustain survival. Read More

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http://dx.doi.org/10.1016/j.cmet.2019.01.011DOI Listing
February 2019
3 Reads

Calcium Signaling Controls Pathogenic Th17 Cell-Mediated Inflammation by Regulating Mitochondrial Function.

Cell Metab 2019 Feb 14. Epub 2019 Feb 14.

Department of Pathology, New York University School of Medicine, New York, NY 10016, USA. Electronic address:

Pathogenic Th17 cells play important roles in many autoimmune and inflammatory diseases. Their function depends on T cell receptor (TCR) signaling and cytokines that activate signal transducer and activator of transcription 3 (STAT3). TCR engagement activates stromal interaction molecule 1 (STIM1) and calcium (Ca) influx through Ca-release-activated Ca (CRAC) channels. Read More

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http://dx.doi.org/10.1016/j.cmet.2019.01.019DOI Listing
February 2019

Glycogen Synthase Kinase-3α Promotes Fatty Acid Uptake and Lipotoxic Cardiomyopathy.

Cell Metab 2019 Feb 2. Epub 2019 Feb 2.

Department of Cell Biology and Molecular Medicine, Cardiovascular Research Institute, Rutgers New Jersey Medical School, Newark, NJ, USA. Electronic address:

Obesity induces lipotoxic cardiomyopathy, a condition in which lipid accumulation in cardiomyocytes causes cardiac dysfunction. Here, we show that glycogen synthase kinase-3α (GSK-3α) mediates lipid accumulation in the heart. Fatty acids (FAs) upregulate GSK-3α, which phosphorylates PPARα at Ser280 in the ligand-binding domain (LBD). Read More

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http://dx.doi.org/10.1016/j.cmet.2019.01.005DOI Listing
February 2019
2 Reads

IGF-2 Preprograms Maturing Macrophages to Acquire Oxidative Phosphorylation-Dependent Anti-inflammatory Properties.

Cell Metab 2019 Feb 4. Epub 2019 Feb 4.

Shanghai Jiao Tong University School of Medicine and Key Laboratory of Tissue Microenvironment and Tumor, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200025, China; The First Affiliated Hospital of Soochow University and State Key Laboratory of Radiation Medicine and Protection, Institutes for Translational Medicine, Soochow University, 199 Renai Road, Suzhou, Jiangsu 215123, China. Electronic address:

Recent investigations revealed that macrophages could be trained with an altered responsiveness, raising the possibility of combating autoimmune diseases by imparting anti-inflammatory capabilities to these cells. While investigating the effect of mesenchymal stem cells on experimental autoimmune encephalomyelitis (EAE), we found a critical role of insulin-like growth factor 2 (IGF-2) in training macrophages to become anti-inflammatory during their maturation. IGF-2 exerts its effects by preprogramming maturing macrophages to commit oxidative phosphorylation (OXPHOS). Read More

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http://dx.doi.org/10.1016/j.cmet.2019.01.006DOI Listing
February 2019
2 Reads
17.565 Impact Factor

A Dozen Years of Discovery: Insights into the Physiology and Pharmacology of FGF21.

Cell Metab 2019 Feb;29(2):246-253

Department of Pharmacology, UT Southwestern Medical Center, Dallas, TX 75390, USA; Howard Hughes Medical Institute, UT Southwestern Medical Center, Dallas, TX 75390, USA. Electronic address:

It has been more than a dozen years since FGF21 burst on the metabolism field in a paper showing that its pharmacologic administration caused weight loss and improved insulin sensitivity and lipoprotein profiles in obese rodents. Since then, FGF21 analogs have advanced all the way to clinical trials, and much progress has been made in understanding FGF21's pharmacology and physiology. In this Perspective, we highlight some of the interesting themes that have emerged from this first dozen years of FGF21 research, including its roles in autocrine/paracrine and endocrine responses to metabolic stress. Read More

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http://dx.doi.org/10.1016/j.cmet.2019.01.004DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6368396PMC
February 2019

Regulatory T Cells under the Mercy of Mitochondria.

Cell Metab 2019 Feb;29(2):243-245

Institut National de la Santé et de la Recherche Médicale, Centre de Recherche des Cordeliers, Sorbonne Université, Université Paris Descartes, Sorbonne Paris Cité, Paris F-75006, France. Electronic address:

Mitochondria, the powerhouse of the cell, known for producing energy through oxidative phosphorylation and the Krebs cycle, continue gaining notoriety for roles beyond bioenergetics. Recently in Nature, Weinberg et al. (2019) reported that mitochondrial complex III is indispensable for suppressive function of regulatory T cells, thus highlighting the importance of mitochondria in immune tolerance. Read More

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https://linkinghub.elsevier.com/retrieve/pii/S15504131193001
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http://dx.doi.org/10.1016/j.cmet.2019.01.012DOI Listing
February 2019
12 Reads