2,491 results match your criteria Cell Metabolism [Journal]


Postprandial Oxidative Metabolism of Human Brown Fat Indicates Thermogenesis.

Cell Metab 2018 Jun 6. Epub 2018 Jun 6.

Turku PET Centre, Turku University Hospital, Kiinamyllynkatu 4-8, 20520 Turku, Finland; Turku PET Centre, University of Turku, Kiinamyllynkatu 4-8, 20520 Turku, Finland; Institute of Public Health and Clinical Nutrition, University of Eastern Finland (UEF), Kuopio, Finland. Electronic address:

Human studies suggest that a meal elevates glucose uptake in brown adipose tissue (BAT). However, in postprandial state the thermogenic activity and the metabolism of non-esterified fatty acids (NEFAs) in BAT remain unclear. Using indirect calorimetry combined with positron emission tomography and computed tomography (PET/CT), we showed that whole-body and BAT thermogenesis (oxygen consumption) increases after the ingestion of a mixed carbohydrate-rich meal, to the same extent as in cold stress. Read More

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June 2018
1 Read

Phospholipase PLA2G6, a Parkinsonism-Associated Gene, Affects Vps26 and Vps35, Retromer Function, and Ceramide Levels, Similar to α-Synuclein Gain.

Cell Metab 2018 Jun 7. Epub 2018 Jun 7.

Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA; Program in Developmental Biology, Baylor College of Medicine, Houston, TX 77030, USA; Howard Hughes Medical Institute, Baylor College of Medicine, Houston, TX 77030, USA; Department of Neuroscience, Baylor College of Medicine, Houston, TX 77030, USA; Jan and Dan Duncan Neurological Research Institute, Texas Children's Hospital, Houston, TX 77030, USA. Electronic address:

Mutations in PLA2G6 (PARK14) cause neurodegenerative disorders in humans, including autosomal recessive neuroaxonal dystrophy and early-onset parkinsonism. We show that loss of iPLA2-VIA, the fly homolog of PLA2G6, reduces lifespan, impairs synaptic transmission, and causes neurodegeneration. Phospholipases typically hydrolyze glycerol phospholipids, but loss of iPLA2-VIA does not affect the phospholipid composition of brain tissue but rather causes an elevation in ceramides. Read More

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June 2018
1 Read

Reversible De-differentiation of Mature White Adipocytes into Preadipocyte-like Precursors during Lactation.

Cell Metab 2018 Jun 8. Epub 2018 Jun 8.

Touchstone Diabetes Center, Department of Internal Medicine, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX 75390-8549, USA. Electronic address:

Adipose tissue in the mammary gland undergoes dramatic remodeling during reproduction. Adipocytes are replaced by mammary alveolar structures during pregnancy and lactation, then reappear upon weaning. The fate of the original adipocytes during lactation and the developmental origin of the re-appearing adipocyte post involution are unclear. Read More

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June 2018
1 Read

Short-Term Fasting Reveals Amino Acid Metabolism as a Major Sex-Discriminating Factor in the Liver.

Cell Metab 2018 Jun 6. Epub 2018 Jun 6.

Center of Excellence on Neurodegenerative Diseases, University of Milan, Milan, Italy; Department of Pharmacological and Biomolecular Sciences, University of Milan, Via Balzaretti 9, Milan 20133, Italy. Electronic address:

Sex impacts on liver physiology with severe consequences for energy metabolism and response to xenobiotic, hepatic, and extra-hepatic diseases. The comprehension of the biology subtending sex-related hepatic differences is therefore very relevant in the medical, pharmacological, and dietary perspective. The extensive application of metabolomics paired to transcriptomics here shows that, in the case of short-term fasting, the decision to maintain lipid synthesis using amino acids (aa) as a source of fuel is the key discriminant for the hepatic metabolism of male and female mice. Read More

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June 2018
1 Read

Supra-Additive Effects of Combining Fat and Carbohydrate on Food Reward.

Cell Metab 2018 Jun 6. Epub 2018 Jun 6.

John B. Pierce Laboratory, New Haven, CT 06519, USA; Department of Psychiatry, Yale University School of Medicine, New Haven, CT 06519, USA; Modern Diet and Physiology Research Center, New Haven, CT 06519, USA. Electronic address:

Post-ingestive signals conveying information about the nutritive properties of food are critical for regulating ingestive behavior. Here, using an auction task concomitant to fMRI scanning, we demonstrate that participants are willing to pay more for fat + carbohydrate compared with equally familiar, liked, and caloric fat or carbohydrate foods and that this potentiated reward is associated with response in areas critical for reward valuation, including the dorsal striatum and mediodorsal thalamus. We also show that individuals are better able to estimate the energy density of fat compared with carbohydrate and fat + carbohydrate foods, an effect associated with functional connectivity between visual (fusiform gyrus) and valuation (ventromedial prefrontal cortex) areas. Read More

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June 2018
1 Read

Acute O Sensing: Role of Coenzyme QH/Q Ratio and Mitochondrial ROS Compartmentalization.

Cell Metab 2018 May 28. Epub 2018 May 28.

Instituto de Biomedicina de Sevilla (IBiS), Hospital Universitario Virgen del Rocío, CSIC, Universidad de Sevilla, Avenida Manuel Siurot s/n, Seville, Spain; Departamento de Fisiología Médica y Biofísica, Facultad de Medicina, Universidad de Sevilla, Seville, Spain; Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Madrid, Spain. Electronic address:

Acute O sensing by peripheral chemoreceptors is essential for mammalian homeostasis. Carotid body glomus cells contain O-sensitive ion channels, which trigger fast adaptive cardiorespiratory reflexes in response to hypoxia. O-sensitive cells have unique metabolic characteristics that favor the hypoxic generation of mitochondrial complex I (MCI) signaling molecules, NADH and reactive oxygen species (ROS), which modulate membrane ion channels. Read More

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Alteration of Tumor Metabolism by CD4+ T Cells Leads to TNF-α-Dependent Intensification of Oxidative Stress and Tumor Cell Death.

Cell Metab 2018 May 30. Epub 2018 May 30.

Georgia Cancer Center, Medical College of Georgia, Augusta University, 1120 15(th) Street, CN-4140, Augusta, GA 30912, USA; Department of Medicine, Medical College of Georgia, Augusta University, Augusta, GA, USA. Electronic address:

The inhibitory effects of cancer on T cell metabolism have been well established, but the metabolic impact of immunotherapy on tumor cells is poorly understood. Here, we developed a CD4+ T cell-based adoptive immunotherapy protocol that was curative for mice with implanted colorectal tumors. By conducting metabolic profiling on tumors, we show that adoptive immunotherapy profoundly altered tumor metabolism, resulting in glutathione depletion and accumulation of reactive oxygen species (ROS) in tumor cells. Read More

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May 2018
4 Reads

Intermittent Fasting Confers Protection in CNS Autoimmunity by Altering the Gut Microbiota.

Cell Metab 2018 Jun;27(6):1222-1235.e6

Department of Neurology, Washington University School of Medicine, Campus Box 8111, 660 S. Euclid Avenue, St. Louis, MO 63110, USA; Hope Center for Neurological Disorders, Washington University School of Medicine, St Louis, MO, USA. Electronic address:

Multiple sclerosis (MS) is more common in western countries with diet being a potential contributing factor. Here we show that intermittent fasting (IF) ameliorated clinical course and pathology of the MS model, experimental autoimmune encephalomyelitis (EAE). IF led to increased gut bacteria richness, enrichment of the Lactobacillaceae, Bacteroidaceae, and Prevotellaceae families and enhanced antioxidative microbial metabolic pathways. Read More

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June 2018
6 Reads

Hallmarks of Brain Aging: Adaptive and Pathological Modification by Metabolic States.

Cell Metab 2018 Jun;27(6):1176-1199

Department of Physiology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore; School of Pharmacy, Sungkyunkwan University, Suwon 16419, Republic of Korea.

During aging, the cellular milieu of the brain exhibits tell-tale signs of compromised bioenergetics, impaired adaptive neuroplasticity and resilience, aberrant neuronal network activity, dysregulation of neuronal Ca homeostasis, the accrual of oxidatively modified molecules and organelles, and inflammation. These alterations render the aging brain vulnerable to Alzheimer's and Parkinson's diseases and stroke. Emerging findings are revealing mechanisms by which sedentary overindulgent lifestyles accelerate brain aging, whereas lifestyles that include intermittent bioenergetic challenges (exercise, fasting, and intellectual challenges) foster healthy brain aging. Read More

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Viral Vectors for Studying Brain Mechanisms that Control Energy Homeostasis.

Cell Metab 2018 Jun;27(6):1168-1175

Program in Integrative Cell Signalling and Neurobiology of Metabolism, Department of Comparative Medicine, Yale University School of Medicine, New Haven, CT 06520, USA; Department of Anatomy and Histology, University of Veterinary Medicine, Budapest 1078, Hungary. Electronic address:

Viral vectors have been shown to be potent and versatile tools for genome editing. In the present Minireview, we focus on lentiviruses and adeno-associated viruses as vectors and their use in the study of the hypothalamic circuits involved in the regulation of energy homeostasis. Read More

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OXPHOS Defects Due to mtDNA Mutations: Glutamine to the Rescue!

Cell Metab 2018 Jun;27(6):1165-1167

Department of Medical Biochemistry, Semmelweis University, Budapest 1094, Hungary. Electronic address:

Mutations in mtDNA associated with OXPHOS defects preclude energy harnessing by OXPHOS. The work of Chen et al. (2018) is previewed, reporting flux pathways of glutamine catabolism in mtDNA mutant cells yielding high-energy phosphates through substrate-level phosphorylation and the influence exerted by the severity of OXPHOS impairment. Read More

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Obesity Protects Cancer from Drugs Targeting Blood Vessels.

Authors:
Yihai Cao

Cell Metab 2018 Jun;27(6):1163-1165

Department of Microbiology, Tumor, and Cell Biology, Karolinska Institutet, 171 77 Stockholm, Sweden. Electronic address:

Drugs that target angiogenesis are commonly used for treating various cancers, but their clinical benefits are limited. In a recent Science Translational Medicine article, Incio et al. (2018) provide mechanistic insight on the role of obesity in the development of anti-VEGF drug resistance in human patients and murine models of breast cancer. Read More

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Visualizing Fatty Acid Flux.

Cell Metab 2018 Jun;27(6):1161-1162

Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, Sweden. Electronic address:

In a recent issue of Cell Metabolism, He et al. (2018) describes a novel technique to visualize cardiac intravascular lipoprotein lipase-mediated processing of triglyceride-rich lipoproteins and then follow the flux of released fatty acids across the endothelium to the underlying cardiomyocytes at high spatial resolution. This allows for detailed analyses of this clearly complex process. Read More

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Watch the Clock, Not the Scale.

Cell Metab 2018 Jun;27(6):1159-1160

Translational Gerontology Branch, National Institute on Aging, NIH, Dickerson, MD 20842, USA. Electronic address:

The prevalence of diabetes is on the rise, leading to astronomical increases in healthcare costs. In this issue of Cell Metabolism, Sutton et al. (2018) report improved metabolic outcomes even without weight loss. Read More

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Of Mice Not Men? Actions of Interleukin-6 on Glucose Tolerance.

Cell Metab 2018 Jun;27(6):1157-1158

Division of Diabetes, Endocrinology and Metabolism, Imperial College London, London, UK. Electronic address:

In mice, interleukin-6 (IL-6) improves glucose tolerance via stimulation of glucagon-like peptide 1 (GLP-1) secretion. In this issue of Cell Metabolism, Lang Lehrskov et al. (2018) demonstrate that IL-6 infusion has GLP-1-dependent and -independent actions with opposing effects on glucose tolerance, resulting in an overall improvement in healthy male volunteers but no improvement in male patients with diabetes. Read More

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Ubiquitination of ABCE1 by NOT4 in Response to Mitochondrial Damage Links Co-translational Quality Control to PINK1-Directed Mitophagy.

Cell Metab 2018 May 18. Epub 2018 May 18.

Department of Pathology, Stanford University School of Medicine, Stanford, CA 94305, USA; Programs in Neuroscience and Cancer Biology, Stanford University School of Medicine, Stanford, CA 94305, USA. Electronic address:

Translation of mRNAs is tightly regulated and constantly surveyed for errors. Aberrant translation can trigger co-translational protein and RNA quality control processes, impairments of which cause neurodegeneration by still poorly understood mechanism(s). Here we show that quality control of translation of mitochondrial outer membrane (MOM)-localized mRNA intersects with the turnover of damaged mitochondria, both orchestrated by the mitochondrial kinase PINK1. Read More

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Weight Gain and Impaired Glucose Metabolism in Women Are Predicted by Inefficient Subcutaneous Fat Cell Lipolysis.

Cell Metab 2018 May 18. Epub 2018 May 18.

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

Adipocyte mobilization of fatty acids (lipolysis) is instrumental for energy expenditure. Lipolysis displays both spontaneous (basal) and hormone-stimulated activity. It is unknown if lipolysis is important for future body weight gain and associated disturbed glucose metabolism, and this was presently investigated in subcutaneous adipocytes from two female cohorts before and after ≥10-year follow-up. Read More

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May 2018
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Cardiolipin Synthesis in Brown and Beige Fat Mitochondria Is Essential for Systemic Energy Homeostasis.

Cell Metab 2018 May 18. Epub 2018 May 18.

Novo Nordisk Foundation Center for Basic Metabolic Research, University of Copenhagen, Copenhagen 2200, Denmark; Department of Biomedical Sciences, University of Copenhagen, Copenhagen 2200, Denmark. Electronic address:

Activation of energy expenditure in thermogenic fat is a promising strategy to improve metabolic health, yet the dynamic processes that evoke this response are poorly understood. Here we show that synthesis of the mitochondrial phospholipid cardiolipin is indispensable for stimulating and sustaining thermogenic fat function. Cardiolipin biosynthesis is robustly induced in brown and beige adipose upon cold exposure. Read More

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May 2018
7 Reads

Patients with Obesity Caused by Melanocortin-4 Receptor Mutations Can Be Treated with a Glucagon-like Peptide-1 Receptor Agonist.

Cell Metab 2018 May 31. Epub 2018 May 31.

Department of Biomedical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen 2200, Denmark; The Novo Nordisk Foundation Center for Basic Metabolic Research, Section for Translational Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen 2200, Denmark. Electronic address:

Pathogenic mutations in the appetite-regulating melanocortin-4 receptor (MC4R) represent the most common cause of monogenic obesity with limited treatment options. Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) cause weight loss by reducing appetite. We assessed the effect of the GLP-1 RA liraglutide 3. Read More

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Chrono-pharmacological Targeting of the CCL2-CCR2 Axis Ameliorates Atherosclerosis.

Cell Metab 2018 May 15. Epub 2018 May 15.

Institute for Cardiovascular Prevention (IPEK), Ludwig Maximilian University, Munich 80336, Germany; German Center for Cardiovascular Research (DZHK), Partner Site Munich Heart Alliance, Munich, Germany; Department of Physiology and Pharmacology (FyFa) and Department of Medicine, Karolinska Institutet, Stockholm 17177, Sweden. Electronic address:

Onset of cardiovascular complications as a consequence of atherosclerosis exhibits a circadian incidence with a peak in the morning hours. Although development of atherosclerosis extends for long periods of time through arterial leukocyte recruitment, we hypothesized that discrete diurnal invasion of the arterial wall could sustain atherogenic growth. Here, we show that myeloid cell recruitment to atherosclerotic lesions oscillates with a peak during the transition from the activity to the resting phase. Read More

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Control of Feeding Behavior by Cerebral Ventricular Volume Transmission of Melanin-Concentrating Hormone.

Cell Metab 2018 May 15. Epub 2018 May 15.

Human and Evolutionary Biology Section, Department of Biological Sciences, University of Southern California, 3616 Trousdale Parkway, AHF-252, Los Angeles, CA 90089-0372, USA; Neuroscience Graduate Program, University of Southern California, Los Angeles, CA 90089, USA. Electronic address:

Classical mechanisms through which brain-derived molecules influence behavior include neuronal synaptic communication and neuroendocrine signaling. Here we provide evidence for an alternative neural communication mechanism that is relevant for food intake control involving cerebroventricular volume transmission of the neuropeptide melanin-concentrating hormone (MCH). Results reveal that the cerebral ventricles receive input from approximately one-third of MCH-producing neurons. Read More

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May 2018
1 Read

Cancer Lipid Metabolism Confers Antiangiogenic Drug Resistance.

Cell Metab 2018 May 25. Epub 2018 May 25.

Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Stockholm 171 77, Sweden. Electronic address:

Intrinsic and evasive antiangiogenic drug (AAD) resistance is frequently developed in cancer patients, and molecular mechanisms underlying AAD resistance remain largely unknown. Here we describe AAD-triggered, lipid-dependent metabolic reprogramming as an alternative mechanism of AAD resistance. Unexpectedly, tumor angiogenesis in adipose and non-adipose environments is equally sensitive to AAD treatment. Read More

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A Role for Hypocretin/Orexin in Metabolic and Sleep Abnormalities in a Mouse Model of Non-metastatic Breast Cancer.

Cell Metab 2018 May 14. Epub 2018 May 14.

Department of Neuroscience, The Ohio State University Wexner Medical Center, Columbus, OH 43210, USA; Neuroscience Research Institute, The Ohio State University Wexner Medical Center, Columbus, OH 43210, USA; Behavioral Neuroendocrinology Group, The Ohio State University Wexner Medical Center, Columbus, OH 43210, USA.

We investigated relationships among immune, metabolic, and sleep abnormalities in mice with non-metastatic mammary cancer. Tumor-bearing mice displayed interleukin-6 (IL-6)-mediated peripheral inflammation, coincident with altered hepatic glucose processing and sleep. Tumor-bearing mice were hyperphagic, had reduced serum leptin concentrations, and enhanced sensitivity to exogenous ghrelin. Read More

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May 2018
6 Reads

Aerobic Glycolysis Controls Myeloid-Derived Suppressor Cells and Tumor Immunity via a Specific CEBPB Isoform in Triple-Negative Breast Cancer.

Cell Metab 2018 May 21. Epub 2018 May 21.

Department of Surgery, University of Michigan School of Medicine, BSRB, 109 Zina Pitcher Place, Ann Arbor, MI 48109-0669, USA; University of Michigan Rogel Cancer Center, University of Michigan School of Medicine, Ann Arbor, MI, USA; Department of Pathology, University of Michigan School of Medicine, Ann Arbor, MI, USA; Graduate Programs in Immunology and Tumor Biology, University of Michigan School of Medicine, Ann Arbor, MI, USA. Electronic address:

Myeloid-derived suppressor cells (MDSCs) inhibit anti-tumor immunity. Aerobic glycolysis is a hallmark of cancer. However, the link between MDSCs and glycolysis is unknown in patients with triple-negative breast cancer (TNBC). Read More

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May 2018
2 Reads

Substantial Metabolic Activity of Human Brown Adipose Tissue during Warm Conditions and Cold-Induced Lipolysis of Local Triglycerides.

Cell Metab 2018 Jun 24;27(6):1348-1355.e4. Epub 2018 May 24.

BHF/University Centre for Cardiovascular Science, University of Edinburgh, The Queen's Medical Research Institute, 47 Little France Crescent, Edinburgh EH16 4TJ, Scotland, UK. Electronic address:

Current understanding of in vivo human brown adipose tissue (BAT) physiology is limited by a reliance on positron emission tomography (PET)/computed tomography (CT) scanning, which has measured exogenous glucose and fatty acid uptake but not quantified endogenous substrate utilization by BAT. Six lean, healthy men underwent fluorodeoxyglucose-PET/CT scanning to localize BAT so microdialysis catheters could be inserted in supraclavicular BAT under CT guidance and in abdominal subcutaneous white adipose tissue (WAT). Arterial and dialysate samples were collected during warm (∼25°C) and cold exposure (∼17°C), and blood flow was measured by xenon washout. Read More

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June 2018
2 Reads

The BCKDH Kinase and Phosphatase Integrate BCAA and Lipid Metabolism via Regulation of ATP-Citrate Lyase.

Cell Metab 2018 Jun 17;27(6):1281-1293.e7. Epub 2018 May 17.

Sarah W. Stedman Nutrition and Metabolism Center & Duke Molecular Physiology Institute, Duke University Medical Center, 300 North Duke Street, Durham, NC 27701, USA; Departments of Medicine and Pharmacology & Cancer Biology, Durham, NC 27701, USA. Electronic address:

Branched-chain amino acids (BCAA) are strongly associated with dysregulated glucose and lipid metabolism, but the underlying mechanisms are poorly understood. We report that inhibition of the kinase (BDK) or overexpression of the phosphatase (PPM1K) that regulates branched-chain ketoacid dehydrogenase (BCKDH), the committed step of BCAA catabolism, lowers circulating BCAA, reduces hepatic steatosis, and improves glucose tolerance in the absence of weight loss in Zucker fatty rats. Phosphoproteomics analysis identified ATP-citrate lyase (ACL) as an alternate substrate of BDK and PPM1K. Read More

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June 2018
4 Reads

The Polycomb-Dependent Epigenome Controls β Cell Dysfunction, Dedifferentiation, and Diabetes.

Cell Metab 2018 Jun 10;27(6):1294-1308.e7. Epub 2018 May 10.

Max Planck Institute of Immunobiology and Epigenetics, Stuebeweg 51, 79108 Freiburg, Germany. Electronic address:

To date, it remains largely unclear to what extent chromatin machinery contributes to the susceptibility and progression of complex diseases. Here, we combine deep epigenome mapping with single-cell transcriptomics to mine for evidence of chromatin dysregulation in type 2 diabetes. We find two chromatin-state signatures that track β cell dysfunction in mice and humans: ectopic activation of bivalent Polycomb-silenced domains and loss of expression at an epigenomically unique class of lineage-defining genes. Read More

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June 2018
1 Read

Arginase 2 Suppresses Renal Carcinoma Progression via Biosynthetic Cofactor Pyridoxal Phosphate Depletion and Increased Polyamine Toxicity.

Cell Metab 2018 Jun 10;27(6):1263-1280.e6. Epub 2018 May 10.

Abramson Family Cancer Research Institute, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA; Department of Cell and Developmental Biology, University of Pennsylvania, Philadelphia, PA 19104, USA. Electronic address:

Kidney cancer, one of the ten most prevalent malignancies in the world, has exhibited increased incidence over the last decade. The most common subtype is "clear cell" renal cell carcinoma (ccRCC), which features consistent metabolic abnormalities, such as highly elevated glycogen and lipid deposition. By integrating metabolomics, genomic, and transcriptomic data, we determined that enzymes in multiple metabolic pathways are universally depleted in human ccRCC tumors, which are otherwise genetically heterogeneous. Read More

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June 2018
2 Reads

Early Time-Restricted Feeding Improves Insulin Sensitivity, Blood Pressure, and Oxidative Stress Even without Weight Loss in Men with Prediabetes.

Cell Metab 2018 Jun 10;27(6):1212-1221.e3. Epub 2018 May 10.

Pennington Biomedical Research Center, Baton Rouge, LA 70808, USA; Department of Nutrition Sciences, University of Alabama at Birmingham, Birmingham, AL 35294, USA. Electronic address:

Intermittent fasting (IF) improves cardiometabolic health; however, it is unknown whether these effects are due solely to weight loss. We conducted the first supervised controlled feeding trial to test whether IF has benefits independent of weight loss by feeding participants enough food to maintain their weight. Our proof-of-concept study also constitutes the first trial of early time-restricted feeding (eTRF), a form of IF that involves eating early in the day to be in alignment with circadian rhythms in metabolism. Read More

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June 2018
2 Reads

Mitochondrial Translation Efficiency Controls Cytoplasmic Protein Homeostasis.

Cell Metab 2018 Jun 10;27(6):1309-1322.e6. Epub 2018 May 10.

Department of Biochemistry and Biophysics, Stockholm University, SE-10691 Stockholm, Sweden. Electronic address:

Cellular proteostasis is maintained via the coordinated synthesis, maintenance, and breakdown of proteins in the cytosol and organelles. While biogenesis of the mitochondrial membrane complexes that execute oxidative phosphorylation depends on cytoplasmic translation, it is unknown how translation within mitochondria impacts cytoplasmic proteostasis and nuclear gene expression. Here we have analyzed the effects of mutations in the highly conserved accuracy center of the yeast mitoribosome. Read More

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June 2018
1 Read

Interleukin-6 Delays Gastric Emptying in Humans with Direct Effects on Glycemic Control.

Cell Metab 2018 Jun 3;27(6):1201-1211.e3. Epub 2018 May 3.

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

Gastric emptying is a critical regulator of postprandial glucose and delayed gastric emptying is an important mechanism of improved glycemic control achieved by short-acting glucagon-like peptide-1 (GLP-1) analogs in clinical practice. Here we report on a novel regulatory mechanism of gastric emptying in humans. We show that increasing interleukin (IL)-6 concentrations delays gastric emptying leading to reduced postprandial glycemia. Read More

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June 2018
1 Read

Glucose Homeostasis Is Important for Immune Cell Viability during Candida Challenge and Host Survival of Systemic Fungal Infection.

Cell Metab 2018 May;27(5):988-1006.e7

Infection and Immunity Program and the Department of Biochemistry and Molecular Biology, Biomedicine Discovery Institute, Monash University, Clayton 3800, VIC, Australia. Electronic address:

To fight infections, macrophages undergo a metabolic shift whereby increased glycolysis fuels antimicrobial inflammation and killing of pathogens. Here we demonstrate that the pathogen Candida albicans turns this metabolic reprogramming into an Achilles' heel for macrophages. During Candida-macrophage interactions intertwined metabolic shifts occur, with concomitant upregulation of glycolysis in both host and pathogen setting up glucose competition. Read More

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May 2018
2 Reads

Maximizing Cellular Adaptation to Endurance Exercise in Skeletal Muscle.

Cell Metab 2018 May;27(5):962-976

Exercise and Nutrition Research Program, Mary MacKillop Institute for Health Research, Australian Catholic University, Melbourne, VIC 3000, Australia; Department of Sport Nutrition, Australian Institute of Sport, Belconnen, ACT, Australia.

The application of molecular techniques to exercise biology has provided novel insight into the complexity and breadth of intracellular signaling networks involved in response to endurance-based exercise. Here we discuss several strategies that have high uptake by athletes and, on mechanistic grounds, have the potential to promote cellular adaptation to endurance training in skeletal muscle. Such approaches are based on the underlying premise that imposing a greater metabolic load and provoking extreme perturbations in cellular homeostasis will augment acute exercise responses that, when repeated over months and years, will amplify training adaptation. Read More

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May 2018
1 Read

Toward an Understanding of How Immune Cells Control Brown and Beige Adipobiology.

Cell Metab 2018 May;27(5):954-961

Departament de Bioquímica i Biomedicina Molecular, Universitat de Barcelona, Barcelona, Catalonia, Spain; CIBER Fisiopatología de la Obesidad y Nutrición, Barcelona, Catalonia, Spain.

Immune cells were recently found to have an unexpected involvement in controlling the thermogenic activity of brown and beige adipose tissue. Here, we review how macrophages, eosinophils, type 2 innate lymphoid cells, and T lymphocytes are linked to this process. In particular, the recruitment of alternatively activated macrophages and eosinophils is associated with brown fat activation and white fat browning. Read More

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May 2018
1 Read

Cold Temperatures Fire up Circadian Neurons.

Cell Metab 2018 May;27(5):951-953

Howard Hughes Medical Institute, University of Pennsylvania, Philadelphia, PA, USA.

Circadian clocks monitor both light and temperature cycles to entrain behavior and physiology to the environment. Recently in Nature, Yadlapalli et al. (2018) identified a subgroup of Drosophila clock neurons that responds to temperature input with changes in intracellular calcium and mediates effects of temperature on circadian entrainment and sleep. Read More

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May 2018
1 Read

Hold the Door: Role of the Gut Barrier in Diabetes.

Cell Metab 2018 May;27(5):949-951

Inflammatory Bowel and Immunobiology Research Institute, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA; Department of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA. Electronic address:

While metabolic tissues such as adipose, liver, muscle, and pancreas have been extensively studied in dysmetabolism, the contribution of the gut remains poorly understood. In a recent Science article, Thaiss et al. (2018) unravel mechanisms underlying intestinal permeability observed in obesity and link barrier dysfunction and risk for infection with hyperglycemia. Read More

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May 2018
1 Read

Asparagine and Glutamine: Co-conspirators Fueling Metastasis.

Cell Metab 2018 May;27(5):947-949

University of Michigan Comprehensive Cancer Center and Department of Internal Medicine, Division of Hematology and Oncology, University of Michigan, Ann Arbor, MI 48109, USA. Electronic address:

Cancer cells frequently hijack normal metabolic pathways to promote their growth and metastasis. Two recent papers by Knott et al. (2018) and Pavlova et al. Read More

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May 2018
1 Read

A Strategy for Discovery of Endocrine Interactions with Application to Whole-Body Metabolism.

Cell Metab 2018 May;27(5):1138-1155.e6

Department of Medicine, 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, CA, USA. Electronic address:

Inter-tissue communication via secreted proteins has been established as a vital mechanism for proper physiologic homeostasis. Here, we report a bioinformatics framework using a mouse reference population, the Hybrid Mouse Diversity Panel (HMDP), which integrates global multi-tissue expression data and publicly available resources to identify and functionally annotate novel circuits of tissue-tissue communication. We validate this method by showing that we can identify known as well as novel endocrine factors responsible for communication between tissues. Read More

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May 2018
2 Reads

12,13-diHOME: An Exercise-Induced Lipokine that Increases Skeletal Muscle Fatty Acid Uptake.

Cell Metab 2018 May;27(5):1111-1120.e3

Section on Integrative Physiology and Metabolism, Joslin Diabetes Center, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, One Joslin Place, Boston, MA 02215, USA. Electronic address:

Circulating factors released from tissues during exercise have been hypothesized to mediate some of the health benefits of regular physical activity. Lipokines are circulating lipid species that have recently been reported to affect metabolism in response to cold. Here, lipidomics analysis revealed that a bout of moderate-intensity exercise causes a pronounced increase in the circulating lipid 12,13-dihydroxy-9Z-octadecenoic acid (12,13-diHOME) in male, female, young, old, sedentary, and active human subjects. Read More

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May 2018
1 Read

A Potent and Specific CD38 Inhibitor Ameliorates Age-Related Metabolic Dysfunction by Reversing Tissue NAD Decline.

Cell Metab 2018 May;27(5):1081-1095.e10

Signal Transduction and Molecular Nutrition Laboratory, Kogod Aging Center, Department of Anesthesiology and Perioperative Medicine, Mayo Clinic College of Medicine, 222 3rd Avenue SW, Rochester, MN 55905, USA. Electronic address:

Aging is characterized by the development of metabolic dysfunction and frailty. Recent studies show that a reduction in nicotinamide adenine dinucleotide (NAD) is a key factor for the development of age-associated metabolic decline. We recently demonstrated that the NADase CD38 has a central role in age-related NAD decline. Read More

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May 2018
5 Reads

NanoSIMS Analysis of Intravascular Lipolysis and Lipid Movement across Capillaries and into Cardiomyocytes.

Cell Metab 2018 May;27(5):1055-1066.e3

Department of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA; Centre for Microscopy, Characterisation and Analysis, University of Western Australia, Perth 6009, Australia. Electronic address:

The processing of triglyceride-rich lipoproteins (TRLs) in capillaries provides lipids for vital tissues, but our understanding of TRL metabolism is limited, in part because TRL processing and lipid movement have never been visualized. To investigate the movement of TRL-derived lipids in the heart, mice were given an injection of [H]triglyceride-enriched TRLs, and the movement of H-labeled lipids across capillaries and into cardiomyocytes was examined by NanoSIMS. TRL processing and lipid movement in tissues were extremely rapid. Read More

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May 2018
3 Reads

DGAT2 Inhibition Alters Aspects of Triglyceride Metabolism in Rodents but Not in Non-human Primates.

Cell Metab 2018 Jun 26;27(6):1236-1248.e6. Epub 2018 Apr 26.

Division of Cardio Metabolic Disease, Merck & Co., Inc., Kenilworth, NJ 07033, USA. Electronic address:

Diacylglycerol acyltransferase 2 (DGAT2) catalyzes the final step in triglyceride (TG) synthesis and has been shown to play a role in regulating hepatic very-low-density lipoprotein (VLDL) production in rodents. To explore the potential of DGAT2 as a therapeutic target for the treatment of dyslipidemia, we tested the effects of small-molecule inhibitors and gene silencing both in vitro and in vivo. Consistent with prior reports, chronic inhibition of DGAT2 in a murine model of obesity led to correction of multiple lipid parameters. Read More

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June 2018
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FGF21 Prevents Angiotensin II-Induced Hypertension and Vascular Dysfunction by Activation of ACE2/Angiotensin-(1-7) Axis in Mice.

Cell Metab 2018 Jun 26;27(6):1323-1337.e5. Epub 2018 Apr 26.

School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou 325035, China; The First Affiliated Hospital of Jinan University, Guangzhou 510630, China. Electronic address:

Fibroblast growth factor 21 (FGF21) is a metabolic hormone with pleiotropic effects on glucose and lipid metabolism and insulin sensitivity. However, the role of FGF21 in hypertension remains elusive. Here we show that FGF21 deficiency significantly exacerbates angiotensin II-induced hypertension and vascular dysfunction, whereas such negative effects are reversed by replenishment of FGF21. Read More

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June 2018
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Aldolase B-Mediated Fructose Metabolism Drives Metabolic Reprogramming of Colon Cancer Liver Metastasis.

Cell Metab 2018 Jun 26;27(6):1249-1262.e4. Epub 2018 Apr 26.

Department of Biomedical Engineering, Duke University, Durham, NC 27708, USA. Electronic address:

Cancer metastasis accounts for the majority of cancer-related deaths and remains a clinical challenge. Metastatic cancer cells generally resemble cells of the primary cancer, but they may be influenced by the milieu of the organs they colonize. Here, we show that colorectal cancer cells undergo metabolic reprogramming after they metastasize and colonize the liver, a key metabolic organ. Read More

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June 2018
4 Reads

Quantitative Analysis of NAD Synthesis-Breakdown Fluxes.

Cell Metab 2018 May;27(5):1067-1080.e5

Lewis-Sigler Institute for Integrative Genomics, Princeton University, Princeton, NJ 08540, USA; Department of Chemistry, Princeton University, Princeton, NJ 08540, USA; Diabetes Research Center, University of Pennsylvania, Philadelphia, PA 19104, USA. Electronic address:

The redox cofactor nicotinamide adenine dinucleotide (NAD) plays a central role in metabolism and is a substrate for signaling enzymes including poly-ADP-ribose-polymerases (PARPs) and sirtuins. NAD concentration falls during aging, which has triggered intense interest in strategies to boost NAD levels. A limitation in understanding NAD metabolism has been reliance on concentration measurements. Read More

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