2,654 results match your criteria Cell Metabolism [Journal]


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
1 Read

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

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
6 Reads

mTOR Is Key to T Cell Transdifferentiation.

Cell Metab 2019 Feb;29(2):241-242

School of Life Sciences and Technology, ShanghaiTech University. Electronic address:

T cell transdifferentiation to functionally distinct subsets can play a key role in balancing the protective and pathogenic features of the T cell response. In a new study, Karmaus et al. (2019) showed that mTORC1 activity influences metabolic heterogeneity within a T cell population to modulate transdifferentiation and disease pathogenesis in a setting of chronic inflammation-driven autoimmunity. Read More

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http://dx.doi.org/10.1016/j.cmet.2019.01.008DOI Listing
February 2019

Host Control of Tumor Feeding: Autophagy Holds the Key.

Cell Metab 2019 Feb;29(2):236-238

Department of Anatomy, University of California, San Francisco, San Francisco, CA 94143, USA; Department of Pathology, University of California, San Francisco, San Francisco, CA 94143, USA; Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, CA 94158, USA. Electronic address:

Cancer cells are dependent on functional autophagy both within their cytoplasm and systemically in the host to maintain growth. How systemic autophagy directly contributes to tumor growth remains unclear. In a study published in Nature, Poillet-Perez et al. Read More

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http://dx.doi.org/10.1016/j.cmet.2019.01.009DOI Listing
February 2019
2 Reads

Death Eaters Rely on Metabolic Signaling to Wield Anti-inflammatory Responses.

Cell Metab 2019 Feb;29(2):234-236

University of Ottawa Heart Institute, 40 Ruskin Street, Ottawa, ON K1Y 4W7, Canada. Electronic address:

Efferocytosis, the process by which dying or dead cells are removed by phagocytes, is essential to tissue homeostasis. However, how these "death eaters" or efferocytes coordinate phagocytosis with their immune function is incompletely understood. In this issue, Zhang et al. Read More

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http://dx.doi.org/10.1016/j.cmet.2019.01.010DOI Listing
February 2019

Inhibiting Glutamine-Dependent mTORC1 Activation Ameliorates Liver Cancers Driven by β-Catenin Mutations.

Cell Metab 2019 Jan 28. Epub 2019 Jan 28.

Division of Experimental Pathology, Department of Pathology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA; Pittsburgh Liver Research Center, University of Pittsburgh Medical Center and University of Pittsburgh School of Medicine, Pittsburgh, PA, USA; Division of Gastroenterology, Hepatology and Nutrition, Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA. Electronic address:

Based on their lobule location, hepatocytes display differential gene expression, including pericentral hepatocytes that surround the central vein, which are marked by Wnt-β-catenin signaling. Activating β-catenin mutations occur in a variety of liver tumors, including hepatocellular carcinoma (HCC), but no specific therapies are available to treat these tumor subsets. Here, we identify a positive relationship between β-catenin activation, its transcriptional target glutamine synthetase (GS), and p-mTOR-S2448, an indicator of mTORC1 activation. Read More

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http://dx.doi.org/10.1016/j.cmet.2019.01.002DOI Listing
January 2019

Multiplexed In Situ Imaging Mass Cytometry Analysis of the Human Endocrine Pancreas and Immune System in Type 1 Diabetes.

Cell Metab 2019 Jan 28. Epub 2019 Jan 28.

Department of Genetics and Institute for Diabetes, Obesity and Metabolism, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA. Electronic address:

The interaction between the immune system and endocrine cells in the pancreas is crucial for the initiation and progression of type 1 diabetes (T1D). Imaging mass cytometry (IMC) enables multiplexed assessment of the abundance and localization of more than 30 proteins on the same tissue section at 1-μm resolution. Herein, we have developed a panel of 33 antibodies that allows for the quantification of key cell types including pancreatic exocrine cells, islet cells, immune cells, and stromal components. Read More

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http://dx.doi.org/10.1016/j.cmet.2019.01.003DOI Listing
January 2019

A Map of Human Type 1 Diabetes Progression by Imaging Mass Cytometry.

Cell Metab 2019 Jan 11. Epub 2019 Jan 11.

Institute of Molecular Life Sciences, University of Zurich, Zurich, Switzerland. Electronic address:

Type 1 diabetes (T1D) results from the autoimmune destruction of insulin-producing β cells. A comprehensive picture of the changes during T1D development is lacking due to limited sample availability, inability to sample longitudinally, and the paucity of technologies enabling comprehensive tissue profiling. Here, we analyzed 1,581 islets from 12 human donors, including eight with T1D, using imaging mass cytometry (IMC). Read More

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https://linkinghub.elsevier.com/retrieve/pii/S15504131183069
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http://dx.doi.org/10.1016/j.cmet.2018.11.014DOI Listing
January 2019
5 Reads

Oxyphor 2P: A High-Performance Probe for Deep-Tissue Longitudinal Oxygen Imaging.

Cell Metab 2019 Jan 9. Epub 2019 Jan 9.

Department of Biochemistry and Biophysics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA; Department of Chemistry, School of Arts and Sciences, University of Pennsylvania, Philadelphia, PA 19104, USA. Electronic address:

Quantitative imaging of oxygen distributions in tissue can provide invaluable information about metabolism in normal and diseased states. Two-photon phosphorescence lifetime microscopy (2PLM) has been developed to perform measurements of oxygen in vivo with micron-scale resolution in 3D; however, the method's potential has not yet been fully realized due to the limitations of current phosphorescent probe technology. Here, we report a new sensor, Oxyphor 2P, that enables oxygen microscopy twice as deep (up to 600 μm below the tissue surface) and with ∼60 times higher speed than previously possible. Read More

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http://dx.doi.org/10.1016/j.cmet.2018.12.022DOI Listing
January 2019

Polyunsaturated Fatty Acid Desaturation Is a Mechanism for Glycolytic NAD Recycling.

Cell Metab 2019 Jan 14. Epub 2019 Jan 14.

Nephrology Division, Massachusetts General Hospital, Boston, MA 02114, USA; Endocrine Unit, Massachusetts General Hospital, Boston, MA 02114, USA; Metabolism Program, Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA. Electronic address:

The reactions catalyzed by the delta-5 and delta-6 desaturases (D5D/D6D), key enzymes responsible for highly unsaturated fatty acid (HUFA) synthesis, regenerate NAD from NADH. Here, we show that D5D/D6D provide a mechanism for glycolytic NAD recycling that permits ongoing glycolysis and cell viability when the cytosolic NAD/NADH ratio is reduced, analogous to lactate fermentation. Although lesser in magnitude than lactate production, this desaturase-mediated NAD recycling is acutely adaptive when aerobic respiration is impaired in vivo. Read More

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http://dx.doi.org/10.1016/j.cmet.2018.12.023DOI Listing
January 2019

Activation of Anxiogenic Circuits Instigates Resistance to Diet-Induced Obesity via Increased Energy Expenditure.

Cell Metab 2019 Jan 11. Epub 2019 Jan 11.

Department of Neuroscience, The Scripps Research Institute Florida, Jupiter, FL 33458, USA. Electronic address:

Anxiety disorders are associated with body weight changes in humans. However, the mechanisms underlying anxiety-induced weight changes remain poorly understood. Using Emx1 mice, we deleted the gene for brain-derived neurotrophic factor (BDNF) in the cortex, hippocampus, and some amygdalar subregions. Read More

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http://dx.doi.org/10.1016/j.cmet.2018.12.018DOI Listing
January 2019
2 Reads

ACOT12-Dependent Alteration of Acetyl-CoA Drives Hepatocellular Carcinoma Metastasis by Epigenetic Induction of Epithelial-Mesenchymal Transition.

Cell Metab 2019 Jan 16. Epub 2019 Jan 16.

Department of General Surgery, Huashan Hospital, Cancer Metastasis Institute, Fudan University, 12 Urumqi Road (M), Shanghai 200040, China; Institutes of Biomedical Sciences, Fudan University, Shanghai 200032, China. Electronic address:

Metabolic reprogramming plays an important role in supporting tumor growth. However, little is known about the metabolic alterations that promote cancer metastasis. In this study, we identify acyl-CoA thioesterase 12 (ACOT12) as a key player in hepatocellular carcinoma (HCC) metastasis. Read More

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http://dx.doi.org/10.1016/j.cmet.2018.12.019DOI Listing
January 2019
7 Reads

Autoregulation of Osteocyte Sema3A Orchestrates Estrogen Action and Counteracts Bone Aging.

Cell Metab 2019 Jan 17. Epub 2019 Jan 17.

Department of Immunology, Graduate School of Medicine and Faculty of Medicine, The University of Tokyo, Tokyo 113-0033, Japan. Electronic address:

Osteocyte survival is key to bone homeostasis and is perturbed in menopause and aging. However, it remains unknown how osteocyte-mediated maintenance of the skeleton is regulated by the osteoprotective factor semaphorin 3A (Sema3A), a secreted protein that is known to reduce bone resorption and enhance bone formation. Here, we show that estrogen induces osteocyte expression of Sema3A, which acts on its receptor on osteocytes to promote their survival and maintain bone homeostasis. Read More

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http://dx.doi.org/10.1016/j.cmet.2018.12.021DOI Listing
January 2019
1 Read

Loss of BCAA Catabolism during Carcinogenesis Enhances mTORC1 Activity and Promotes Tumor Development and Progression.

Cell Metab 2019 Jan 8. Epub 2019 Jan 8.

Singapore Bioimaging Consortium, Agency for Science, Technology, and Research, 11 Biopolis Way, 138667 Singapore, Singapore. Electronic address:

Tumors display profound changes in cellular metabolism, yet how these changes aid the development and growth of tumors is not fully understood. Here we use a multi-omic approach to examine liver carcinogenesis and regeneration, and find that progressive loss of branched-chain amino acid (BCAA) catabolism promotes tumor development and growth. In human hepatocellular carcinomas and animal models of liver cancer, suppression of BCAA catabolic enzyme expression led to BCAA accumulation in tumors, though this was not observed in regenerating liver tissues. Read More

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http://dx.doi.org/10.1016/j.cmet.2018.12.020DOI Listing
January 2019
1 Read
17.565 Impact Factor

Gene-by-Sex Interactions in Mitochondrial Functions and Cardio-Metabolic Traits.

Cell Metab 2019 Jan 8. Epub 2019 Jan 8.

Department of Medicine/Division of Cardiology and Department of Human Genetics, University of California, Los Angeles, Los Angeles, CA, USA; Department of Human Genetics, University of California, Los Angeles, Los Angeles, CA, USA; Department of Microbiology, Immunology and Molecular Genetics, University of California, Los Angeles, Los Angeles, CA, USA. Electronic address:

We studied sex differences in over 50 cardio-metabolic traits in a panel of 100 diverse inbred strains of mice. The results clearly showed that the effects of sex on both clinical phenotypes and gene expression depend on the genetic background. In support of this, genetic loci associated with the traits frequently showed sex specificity. Read More

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http://dx.doi.org/10.1016/j.cmet.2018.12.013DOI Listing
January 2019
2 Reads

GDF15 Provides an Endocrine Signal of Nutritional Stress in Mice and Humans.

Cell Metab 2019 Jan 2. Epub 2019 Jan 2.

Metabolic Research Laboratories, Wellcome Trust-Medical Research Council Institute of Metabolic Science, University of Cambridge, Cambridge CB2 0QQ, UK. Electronic address:

GDF15 is an established biomarker of cellular stress. The fact that it signals via a specific hindbrain receptor, GFRAL, and that mice lacking GDF15 manifest diet-induced obesity suggest that GDF15 may play a physiological role in energy balance. We performed experiments in humans, mice, and cells to determine if and how nutritional perturbations modify GDF15 expression. Read More

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https://linkinghub.elsevier.com/retrieve/pii/S15504131183075
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http://dx.doi.org/10.1016/j.cmet.2018.12.016DOI Listing
January 2019
5 Reads
17.565 Impact Factor

Moving beyond GWAS and eQTL Analysis to Validated Hits in Chronic Kidney Disease.

Cell Metab 2019 Jan;29(1):9-10

Department of Nephrology and Hypertension, University of Erlangen, Erlangen, Germany. Electronic address:

Genome-wide association studies (GWAS) have identified multiple chronic kidney disease (CKD)-associated single-nucleotide polymorphisms (SNPs) mainly localized to non-coding genomic regions. To understand which genes and which cell types are affected by these genetic variants, compartment-specific transcriptome, genome, and epigenome data were analyzed in an integrative manner in a recent study by Qiu et al. (Qiu et al. Read More

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http://dx.doi.org/10.1016/j.cmet.2018.12.009DOI Listing
January 2019
1 Read

A "Connexin" Responsible for the Fatal Attraction of Cancer to Bone.

Cell Metab 2019 Jan;29(1):6-8

Indiana University School of Medicine, Department of Medicine and IU Simon Cancer Center, Indianapolis, IN, USA. Electronic address:

Tumor cell interactions with the bone microenvironment are vital for the establishment and progression of bone metastases. Recently in Cancer Cell, Wang et al. (2018) showed that cells of the osteoblast lineage are critical for the delivery of calcium to tumor cells through gap junctions, pointing toward potential therapies for bone metastases. Read More

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http://dx.doi.org/10.1016/j.cmet.2018.12.014DOI Listing
January 2019
1 Read

Complement C3 and Autophagy Keep the β Cell Alive.

Cell Metab 2019 Jan;29(1):4-6

Department of Medicine, Albert Einstein College of Medicine, Bronx, NY 10461, USA; Department of Molecular Pharmacology, Albert Einstein College of Medicine, Bronx, NY 10461, USA; Institute for Aging Research, Albert Einstein College of Medicine, Bronx, NY 10461, USA; Einstein-Mount Sinai Diabetes Research Center, Albert Einstein College of Medicine, Bronx, NY 10461, USA; The Fleischer Institute for Diabetes and Metabolism, Albert Einstein College of Medicine, Bronx, NY 10461, USA. Electronic address:

Autophagy prevents pancreatic β cell death during obesity, although the mechanism of autophagy activation in the β cell has remained elusive. In this issue of Cell Metabolism, King et al. (2018) show that intracellular complement component C3 interacts with autophagy protein ATG16L1 and protects against β cell death by stimulating autophagy. Read More

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http://dx.doi.org/10.1016/j.cmet.2018.12.010DOI Listing
January 2019
7 Reads

NASH and HCC Are Driven by Different Signaling Pathways with a Common Regulator.

Authors:
Wajahat Mehal

Cell Metab 2019 Jan;29(1):3-4

Section of Digestive Diseases, Yale University, New Haven, CT 06405, USA; West Haven VA, West Haven, CT 06516, USA. Electronic address:

Oxidative stress is uniformly present in non-alcoholic steatohepatitis (NASH), but its role in the development of liver inflammation and hepatocellular cancer (HCC) and the relationship between these two pathologies are poorly understood. In a recent issue of Cell, Grohmann et al. (2018) demonstrate a vital role of obesity-induced oxidative stress in deactivating the phosphatase TCPTP, resulting in activation of STAT-1 and STAT-3, which each independently drive the development of NASH and HCC, respectively. Read More

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http://dx.doi.org/10.1016/j.cmet.2018.12.012DOI Listing
January 2019
1 Read

β Cell Dysfunction in Type 2 Diabetes: Drained of Energy?

Cell Metab 2019 Jan;29(1):1-2

Oxford Centre for Diabetes, Endocrinology and Metabolism, University of Oxford, Churchill Hospital, Oxford OX3 7LJ, UK; Metabolic Physiology, Department of Physiology, University of Göteborg, Box 430, SE-405 30 Göteborg, Sweden. Electronic address:

Type 2 diabetes is a progressive disorder, but exactly how the progression occurs remains unknown. In this issue of Cell Metabolism, Zhang et al. (2019) present evidence that diabetes, via hyperglycemia, leads to aberrant insertion of a mitochondrial ion channel in the plasma membrane, rendering it leaky to key intracellular signaling molecules with resultant suppression of insulin secretion. Read More

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http://dx.doi.org/10.1016/j.cmet.2018.12.015DOI Listing
January 2019
1 Read

AMPK-Mediated Lysosome Biogenesis in Lung Cancer Growth.

Cell Metab 2019 Feb 3;29(2):238-240. Epub 2019 Jan 3.

Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston, MA 02114, USA; Center for Regenerative Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA; Broad Institute of Harvard and Massachusetts Institute of Technology, Boston, MA 02113, USA. Electronic address:

Cancer cells must adapt to metabolic stress during tumor progression. In this issue of Cell Metabolism, Eichner et al. (2019) report that lung cancer development in genetically engineered mice requires the energy sensor AMP-activated protein kinase (AMPK). Read More

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http://dx.doi.org/10.1016/j.cmet.2018.12.011DOI Listing
February 2019
1 Read

Obesity-Induced Cellular Senescence Drives Anxiety and Impairs Neurogenesis.

Cell Metab 2019 Jan 3. Epub 2019 Jan 3.

Institute for Cell and Molecular Biosciences, Newcastle University Institute for Ageing, Campus for Ageing and Vitality, Newcastle upon Tyne NE4 5PL, UK; Robert and Arlene Kogod Center on Aging, Mayo Clinic, 200 First Street SW, Rochester, MN 55905, USA; Department of Physiology and Biomedical Engineering, Mayo Clinic, Rochester, MN 55905, USA. Electronic address:

Cellular senescence entails a stable cell-cycle arrest and a pro-inflammatory secretory phenotype, which contributes to aging and age-related diseases. Obesity is associated with increased senescent cell burden and neuropsychiatric disorders, including anxiety and depression. To investigate the role of senescence in obesity-related neuropsychiatric dysfunction, we used the INK-ATTAC mouse model, from which p16-expressing senescent cells can be eliminated, and senolytic drugs dasatinib and quercetin. Read More

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http://dx.doi.org/10.1016/j.cmet.2018.12.008DOI Listing
January 2019
9 Reads

Efferocytosis Fuels Requirements of Fatty Acid Oxidation and the Electron Transport Chain to Polarize Macrophages for Tissue Repair.

Cell Metab 2019 Feb 27;29(2):443-456.e5. Epub 2018 Dec 27.

Department of Pathology, Feinberg School of Medicine, Chicago, IL, USA; Feinberg Cardiovascular & Renal Research Institute, Feinberg School of Medicine, Chicago, IL, USA. Electronic address:

During wound injury, efferocytosis fills the macrophage with a metabolite load nearly equal to the phagocyte itself. A timely question pertains to how metabolic phagocytic signaling regulates the signature anti-inflammatory macrophage response. Here we report the metabolome of activated macrophages during efferocytosis to reveal an interleukin-10 (IL-10) cytokine escalation that was independent of glycolysis yet bolstered by apoptotic cell fatty acids and mitochondrial β-oxidation, the electron transport chain, and heightened coenzyme NAD. Read More

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http://dx.doi.org/10.1016/j.cmet.2018.12.004DOI Listing
February 2019
1 Read

Is Energy Balance in Pregnancy Involved in the Etiology of Gestational Diabetes in Women with Obesity?

Cell Metab 2019 Feb 27;29(2):231-233. Epub 2018 Dec 27.

Clinical Sciences Division, Pennington Biomedical Research Center, 6400 Perkins Road, Baton Rouge, LA 70808, USA. Electronic address:

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https://linkinghub.elsevier.com/retrieve/pii/S15504131183073
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http://dx.doi.org/10.1016/j.cmet.2018.12.002DOI Listing
February 2019
2 Reads

Food Intake Recruits Orosensory and Post-ingestive Dopaminergic Circuits to Affect Eating Desire in Humans.

Cell Metab 2018 Dec 24. Epub 2018 Dec 24.

Max Planck Institute for Metabolism Research, Cologne, Germany; Cologne Cluster of Excellence in Cellular Stress and Aging-Associated Disease (CECAD), Cologne, Germany; Modern Diet and Physiology Research Center, New Haven, CT, USA.

Pleasant taste and nutritional value guide food selection behavior. Here, orosensory features of food may be secondary to its nutritional value in underlying reinforcement, but it is unclear how the brain encodes the reward value of food. Orosensory and peripheral physiological signals may act together on dopaminergic circuits to drive food intake. Read More

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http://dx.doi.org/10.1016/j.cmet.2018.12.006DOI Listing
December 2018
1 Read

Expansion of Islet-Resident Macrophages Leads to Inflammation Affecting β Cell Proliferation and Function in Obesity.

Cell Metab 2019 Feb 27;29(2):457-474.e5. Epub 2018 Dec 27.

Pediatric Diabetes Research Center, Department of Pediatrics, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA 92093, USA. Electronic address:

The nature of obesity-associated islet inflammation and its impact on β cell abnormalities remains poorly defined. Here, we explore immune cell components of islet inflammation and define their roles in regulating β cell function and proliferation. Islet inflammation in obese mice is dominated by macrophages. Read More

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http://dx.doi.org/10.1016/j.cmet.2018.12.003DOI Listing
February 2019
1 Read

Exercise-Induced Changes in Visceral Adipose Tissue Mass Are Regulated by IL-6 Signaling: A Randomized Controlled Trial.

Cell Metab 2018 Dec 18. Epub 2018 Dec 18.

The Centre of Inflammation and Metabolism and the Centre for Physical Activity Research, Rigshospitalet, University of Copenhagen, 2100 Copenhagen, Denmark.

Visceral adipose tissue is harmful to metabolic health. Exercise training reduces visceral adipose tissue mass, but the underlying mechanisms are not known. Interleukin-6 (IL-6) stimulates lipolysis and is released from skeletal muscle during exercise. Read More

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http://dx.doi.org/10.1016/j.cmet.2018.12.007DOI Listing
December 2018
14 Reads

Combined Inhibition of DYRK1A, SMAD, and Trithorax Pathways Synergizes to Induce Robust Replication in Adult Human Beta Cells.

Cell Metab 2018 Dec 14. Epub 2018 Dec 14.

Diabetes, Obesity, and Metabolism Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA. Electronic address:

Small-molecule inhibitors of dual-specificity tyrosine-regulated kinase 1A (DYRK1A) induce human beta cells to proliferate, generating a labeling index of 1.5%-3%. Here, we demonstrate that combined pharmacologic inhibition of DYRK1A and transforming growth factor beta superfamily (TGFβSF)/SMAD signaling generates remarkable further synergistic increases in human beta cell proliferation (average labeling index, 5%-8%, and as high as 15%-18%), and increases in both mouse and human beta cell numbers. Read More

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http://dx.doi.org/10.1016/j.cmet.2018.12.005DOI Listing
December 2018
25 Reads

Inhibition of Mevalonate Pathway Prevents Adipocyte Browning in Mice and Men by Affecting Protein Prenylation.

Cell Metab 2018 Dec 14. Epub 2018 Dec 14.

Institute of Food, Nutrition, and Health, ETH Zürich, Schorenstrasse 16, Schwerzenbach 8603, Switzerland. Electronic address:

Recent research focusing on brown adipose tissue (BAT) function emphasizes its importance in systemic metabolic homeostasis. We show here that genetic and pharmacological inhibition of the mevalonate pathway leads to reduced human and mouse brown adipocyte function in vitro and impaired adipose tissue browning in vivo. A retrospective analysis of a large patient cohort suggests an inverse correlation between statin use and active BAT in humans, while we show in a prospective clinical trial that fluvastatin reduces thermogenic gene expression in human BAT. Read More

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http://dx.doi.org/10.1016/j.cmet.2018.11.017DOI Listing
December 2018
3 Reads

Single-Cell RNA-Seq of the Pancreatic Islets--a Promise Not yet Fulfilled?

Cell Metab 2018 Dec 20. Epub 2018 Dec 20.

Department of Genetics and Institute for Diabetes, Obesity, and Metabolism, Perelman School of Medicine, University of Pennsylvania, 12-126 Smilow Center for Translational Research, 3400 Civic Center Boulevard, Philadelphia, PA 19104-6145, USA. Electronic address:

In the past 3 years, we have seen a flurry of publications on single-cell RNA sequencing (RNA-seq) analyses of pancreatic islets from mouse and human. This technology holds the promise to refine cell-type signatures and discover cellular heterogeneity among the canonical endocrine cell types such as the glucagon-producing α and insulin-producing β cells, going as far as suggesting new subtypes. In addition, single-cell RNA-seq has the ability to characterize rare endocrine cell types that are not captured by prior bulk analysis. Read More

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http://dx.doi.org/10.1016/j.cmet.2018.11.016DOI Listing
December 2018
1 Read

Cellular Metabolism Is a Major Determinant of HIV-1 Reservoir Seeding in CD4 T Cells and Offers an Opportunity to Tackle Infection.

Cell Metab 2018 Dec 19. Epub 2018 Dec 19.

Institut Pasteur, Unité HIV Inflammation et Persistance, 28 rue du Docteur Roux, 75724 Paris Cedex 15, France. Electronic address:

HIV persists in long-lived infected cells that are not affected by antiretroviral treatment. These HIV reservoirs are mainly located in CD4 T cells, but their distribution is variable in the different subsets. Susceptibility to HIV-1 increases with CD4 T cell differentiation. Read More

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http://dx.doi.org/10.1016/j.cmet.2018.11.015DOI Listing
December 2018
2 Reads

Starvation and Pseudo-Starvation as Drivers of Cancer Metastasis through Translation Reprogramming.

Cell Metab 2019 Feb 20;29(2):254-267. Epub 2018 Dec 20.

Ludwig Institute for Cancer Research, Nuffield Department of Medicine, University of Oxford, Old Road Campus Research Building, Old Road Campus, Headington, Oxford OX3 7DQ, UK. Electronic address:

Considerable progress has been made in identifying microenvironmental signals that effect the reversible phenotypic transitions underpinning the early steps in the metastatic cascade. However, although the general principles underlying metastatic dissemination have been broadly outlined, a common theme that unifies many of the triggers of invasive behavior in tumors has yet to emerge. Here we discuss how many diverse signals that induce invasion converge on the reprogramming of protein translation via phosphorylation of eIF2α, a hallmark of the starvation response. Read More

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http://dx.doi.org/10.1016/j.cmet.2018.11.018DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6365217PMC
February 2019
1 Read

Metabolic Imaging Reveals a Unique Preference of Symmetric Cell Division and Homing of Leukemia-Initiating Cells in an Endosteal Niche.

Cell Metab 2018 Dec 10. Epub 2018 Dec 10.

Department of Pathophysiology, Key Laboratory of Cell Differentiation and Apoptosis of Chinese Ministry of Education, Shanghai Jiao Tong University School of Medicine, 280 South Chongqing Road, Shanghai 200025, China; Shanghai Key Laboratory of Reproductive Medicine, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China. Electronic address:

The metabolic properties of leukemia-initiating cells (LICs) in distinct bone marrow niches and their relationships to cell-fate determinations remain largely unknown. Using a metabolic imaging system with a highly responsive genetically encoded metabolic sensor, SoNar, we reveal that SoNar-high cells are more glycolytic, enriched for higher LIC frequency, and develop leukemia much faster than SoNar-low counterparts in an MLL-AF9-induced murine acute myeloid leukemia model. SoNar-high cells mainly home to and locate in the hypoxic endosteal niche and maintain their activities through efficient symmetric division. Read More

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http://dx.doi.org/10.1016/j.cmet.2018.11.013DOI Listing
December 2018
8 Reads

Non-Canonical Control of Neuronal Energy Status by the Na Pump.

Cell Metab 2018 Nov 27. Epub 2018 Nov 27.

Centro de Estudios Científicos (CECs), Casilla 1469, 5110466 Valdivia, Chile. Electronic address:

Neurons have limited intracellular energy stores but experience acute and unpredictable increases in energy demand. To better understand how these cells repeatedly transit from a resting to active state without undergoing metabolic stress, we monitored their early metabolic response to neurotransmission using ion-sensitive probes and FRET sensors in vitro and in vivo. A short theta burst triggered immediate Na entry, followed by a delayed stimulation of the Na/K ATPase pump. Read More

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http://dx.doi.org/10.1016/j.cmet.2018.11.005DOI Listing
November 2018
3 Reads

Mitochondrial Dynamics Is Critical for the Full Pluripotency and Embryonic Developmental Potential of Pluripotent Stem Cells.

Cell Metab 2018 Dec 1. Epub 2018 Dec 1.

Guangzhou First People's Hospital, School of Medicine and Institutes for Life Sciences, South China University of Technology, Guangzhou 510006, China; National Engineering Research Center for Tissue Restoration and Reconstruction, South China University of Technology, Guangzhou 510006, China; Division of Molecular Medicine, Hefei National Laboratory for Physical Sciences at Microscale, the CAS Key Laboratory of Innate Immunity and Chronic Disease, School of Life Sciences, University of Science and Technology of China, Hefei 230027, China; Key Laboratory of Biomedical Engineering of Guangdong Province, South China University of Technology, Guangzhou 510006, China; Key Laboratory of Biomedical Materials and Engineering of the Ministry of Education, South China University of Technology, Guangzhou 510006, China; Guangzhou Regenerative Medicine and Health Guangdong Laboratory, Guangzhou 510005, China. Electronic address:

While the pluripotency of stem cells is known to determine the fate of embryonic development, the mechanisms underlying the acquisition and maintenance of full pluripotency largely remain elusive. Here, we show that the balance between mitochondrial fission and fusion is critical for the full pluripotency of stem cells. By analyzing induced pluripotent stem cells with differential developmental potential, we found that excess mitochondrial fission is associated with an impaired embryonic developmental potential. Read More

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http://dx.doi.org/10.1016/j.cmet.2018.11.007DOI Listing
December 2018
10 Reads
17.565 Impact Factor

The Circadian Protein Period2 Suppresses mTORC1 Activity via Recruiting Tsc1 to mTORC1 Complex.

Cell Metab 2018 Dec 6. Epub 2018 Dec 6.

Key Laboratory of Metabolism and Molecular Medicine, the Ministry of Education, Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Fudan University, Shanghai 200032, China. Electronic address:

Although emerging evidence indicates an important role of the circadian clock in modulating the diurnal oscillation of mammalian target of rapamycin complex 1 (mTORC1) signaling, the underlying molecular mechanism remains elusive. Here we show that Period2 (Per2), a core clock protein, functions as a scaffold protein to tether tuberous sclerosis complex 1 (Tsc1), Raptor, and mTOR together to specifically suppress the activity of mTORC1 complex. Due to the loss of its inhibition of mTORC1, Per2 deficiency significantly enhances protein synthesis and cell proliferation but reduces autophagy. Read More

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http://dx.doi.org/10.1016/j.cmet.2018.11.006DOI Listing
December 2018
3 Reads

Revisiting How the Brain Senses Glucose-And Why.

Cell Metab 2019 Jan 6;29(1):11-17. Epub 2018 Dec 6.

University of Washington Medicine Diabetes Institute, Department of Medicine, University of Washington at South Lake Union, 750 Republican St, F704, Box 358062, Seattle, WA 98109, USA. Electronic address:

Glucose-sensitive neurons have long been implicated in glucose homeostasis, but how glucose-sensing information is used by the brain in this process remains uncertain. Here, we propose a model in which (1) information relevant to the circulating glucose level is essential to the proper function of this regulatory system, (2) this input is provided by neurons located outside the blood-brain barrier (BBB) (since neurons situated behind the BBB are exposed to glucose in brain interstitial fluid, rather than that in the circulation), and (3) while the efferent limb of this system is comprised of neurons situated behind the BBB, many of these neurons are also glucose sensitive. Precedent for such an organizational scheme is found in the thermoregulatory system, which we draw upon in this framework for understanding the role played by brain glucose sensing in glucose homeostasis. Read More

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http://dx.doi.org/10.1016/j.cmet.2018.11.001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6326855PMC
January 2019
10 Reads

Epithelial-Mesenchymal Transition Directs Stem Cell Polarity via Regulation of Mitofusin.

Cell Metab 2018 Nov 27. Epub 2018 Nov 27.

Department of Basic Medical Sciences, Purdue University, West Lafayette, IN 47907, USA; Center for Cancer Research, Purdue University, West Lafayette, IN 47907, USA. Electronic address:

Mitochondria are dynamic organelles that have been linked to stem cell homeostasis. However, the mechanisms involved in mitochondrial regulation of stem cell fate determination remain elusive. Here we discover that epithelial-mesenchymal transition (EMT), a key process in cancer progression, induces mitochondrial fusion through regulation of the miR200c-PGC1α-MFN1 pathway. Read More

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http://dx.doi.org/10.1016/j.cmet.2018.11.004DOI Listing
November 2018
10 Reads

New Advances in Adaptive Thermogenesis: UCP1 and Beyond.

Cell Metab 2019 Jan 29;29(1):27-37. Epub 2018 Nov 29.

Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, MA, USA; Department of Cell Biology, Harvard Medical School, Boston, MA, USA. Electronic address:

Brown and beige adipocytes can catabolize stored energy to generate heat, and this distinct capacity for thermogenesis could be leveraged as a therapy for metabolic diseases like obesity and type 2 diabetes. Thermogenic adipocytes drive heat production through close coordination of substrate supply with the mitochondrial oxidative machinery and effectors that control the rate of substrate oxidation. Together, this apparatus affords these adipocytes with tremendous capacity to drive thermogenesis. Read More

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http://dx.doi.org/10.1016/j.cmet.2018.11.002DOI Listing
January 2019
1 Read

Can We DECLARE a Victory against Cardio-Renal Disease in Diabetes?

Cell Metab 2018 Dec;28(6):813-815

Division of Cardiac Surgery, Keenan Research Centre for Biomedical Science and Li Ka Shing Knowledge Institute of St. Michael's Hospital, Departments of Surgery, and Pharmacology and Toxicology, University of Toronto, Toronto, ON, Canada. Electronic address:

Heart failure and renal disease remain significant complications in people with type 2 diabetes (T2D). Recent outcome studies with sodium-glucose cotransporter-2 (SGLT2) inhibitors have provided increasing insights, with the latest reporting trial DECLARE-TIMI 58 (Wiviott et al., 2018), pointing toward a role for these agents in the primary prevention of cardio-renal complications in T2D. Read More

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https://linkinghub.elsevier.com/retrieve/pii/S15504131183068
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http://dx.doi.org/10.1016/j.cmet.2018.11.010DOI Listing
December 2018
24 Reads

Parasitic Behavior of Leukemic Cells in Systemic Host Metabolism.

Cell Metab 2018 Dec;28(6):811-813

The Campbell Family Institute for Breast Cancer Research, Ontario Cancer Institute, University Health Network, Departments of Medical Biophysics and Immunology, University of Toronto, Toronto, ON, Canada; The University of Hong Kong, Hong Kong. Electronic address:

Metabolic reprogramming is a hallmark of cancer cell metabolism. Recently, in Cancer Cell, Ye and colleagues (2018) reported that leukemic cells have the capacity to modulate glucose metabolism in multiple organs of their host, thereby increasing the glucose resources available for malignant cell growth. Read More

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https://linkinghub.elsevier.com/retrieve/pii/S15504131183068
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http://dx.doi.org/10.1016/j.cmet.2018.11.011DOI Listing
December 2018
12 Reads

A Gut Feeling for Metformin.

Cell Metab 2018 Dec;28(6):808-810

Toronto General Hospital Research Institute, UHN, Toronto, ON M5G 1L7, Canada; Department of Physiology, University of Toronto, Toronto, ON M5S 1A8, Canada; Department of Medicine, University of Toronto, Toronto, ON M5S 1A8, Canada; Banting and Best Diabetes Centre, University of Toronto, Toronto, ON M5G 2C4, Canada. Electronic address:

Metformin is a first-line glucose-lowering agent in patients with type 2 diabetes (T2D). Recently in Nature Medicine, Sun et al. (2018) reported that short-term metformin therapy decreases gut Bacteroides fragilis, consequently increasing glycoursodexoycholic acid (GUDCA) levels in humans. Read More

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http://dx.doi.org/10.1016/j.cmet.2018.11.012DOI Listing
December 2018
11 Reads