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Molecular Metabolism

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https://www.readbyqxmd.com/read/29681509/regional-differences-in-brain-glucose-metabolism-determined-by-imaging-mass-spectrometry
#1
André Kleinridders, Heather A Ferris, Michelle L Reyzer, Michaela Rath, Marion Soto, M Lisa Manier, Jeffrey Spraggins, Zhihong Yang, Robert C Stanton, Richard M Caprioli, C Ronald Kahn
OBJECTIVE: Glucose is the major energy substrate of the brain and crucial for normal brain function. In diabetes, the brain is subject to episodes of hypo- and hyperglycemia resulting in acute outcomes ranging from confusion to seizures, while chronic metabolic dysregulation puts patients at increased risk for depression and Alzheimer's disease. In the present study, we aimed to determine how glucose is metabolized in different regions of the brain using imaging mass spectrometry (IMS)...
April 6, 2018: Molecular Metabolism
https://www.readbyqxmd.com/read/29673577/profiling-of-g-protein-coupled-receptors-in-vagal-afferents-reveals-novel-gut-to-brain-sensing-mechanisms
#2
Kristoffer L Egerod, Natalia Petersen, Pascal N Timshel, Jens C Rekling, Yibing Wang, Qinghua Liu, Thue W Schwartz, Laurent Gautron
OBJECTIVES: G protein-coupled receptors (GPCRs) act as transmembrane molecular sensors of neurotransmitters, hormones, nutrients, and metabolites. Because unmyelinated vagal afferents richly innervate the gastrointestinal mucosa, gut-derived molecules may directly modulate the activity of vagal afferents through GPCRs. However, the types of GPCRs expressed in vagal afferents are largely unknown. Here, we determined the expression profile of all GPCRs expressed in vagal afferents of the mouse, with a special emphasis on those innervating the gastrointestinal tract...
April 3, 2018: Molecular Metabolism
https://www.readbyqxmd.com/read/29673576/the-role-of-genetic-variation-of-human-metabolism-for-bmi-mental-traits-and-mental-disorders
#3
Johannes Hebebrand, Triinu Peters, Dick Schijven, Moritz Hebebrand, Corinna Grasemann, Thomas W Winkler, Iris M Heid, Jochen Antel, Manuel Föcker, Lisa Tegeler, Lena Brauner, Roger A H Adan, Jurjen J Luykx, Christoph U Correll, Inke R König, Anke Hinney, Lars Libuda
OBJECTIVE: The aim was to assess whether loci associated with metabolic traits also have a significant role in BMI and mental traits/disorders METHODS: We first assessed the number of single nucleotide polymorphisms (SNPs) with genome-wide significance for human metabolism (NHGRI-EBI Catalog). These 516 SNPs (216 independent loci) were looked-up in genome-wide association studies for association with body mass index (BMI) and the mental traits/disorders educational attainment, neuroticism, schizophrenia, well-being, anxiety, depressive symptoms, major depressive disorder, autism-spectrum disorder, attention-deficit/hyperactivity disorder, Alzheimer's disease, bipolar disorder, aggressive behavior, and internalizing problems...
April 3, 2018: Molecular Metabolism
https://www.readbyqxmd.com/read/29656110/targeting-hepatic-pyruvate-dehydrogenase-kinases-restores-insulin-signaling-and-mitigates-chrebp-mediated-lipogenesis-in-diet-induced-obese-mice
#4
Cheng-Yang Wu, Shih-Chia Tso, Jacinta L Chuang, Wen-Jun Gui, Mingliang Lou, Gaurav Sharma, Chalermchai Khemtong, Xiangbing Qi, R Max Wynn, David T Chuang
OBJECTIVE: Mitochondrial pyruvate dehydrogenase kinases 1-4 (PDKs1-4) negatively regulate activity of the pyruvate dehydrogenase complex (PDC) by reversible phosphorylation. PDKs play a pivotal role in maintaining energy homeostasis and contribute to metabolic flexibility by attenuating PDC activity in various mammalian tissues. Cumulative evidence has shown that the up-regulation of PDK4 expression is tightly associated with obesity and diabetes. In this investigation, we test the central hypothesis that PDKs1-4 are a pharmacological target for lowering glucose levels and restoring insulin sensitivity in obesity and type 2 diabetes (T2D)...
March 31, 2018: Molecular Metabolism
https://www.readbyqxmd.com/read/29661693/phosphorylation-of-beta-3-adrenergic-receptor-at-serine-247-by-erk-map-kinase-drives-lipolysis-in-obese-adipocytes
#5
Shangyu Hong, Wei Song, Peter-James H Zushin, Bingyang Liu, Mark P Jedrychowski, Amir I Mina, Zhaoming Deng, Dimitrije Cabarkapa, Jessica A Hall, Colin J Palmer, Hassan Aliakbarian, John Szpyt, Steven P Gygi, Ali Tavakkoli, Lydia Lynch, Norbert Perrimon, Alexander S Banks
OBJECTIVE: The inappropriate release of free fatty acids from obese adipose tissue stores has detrimental effects on metabolism, but key molecular mechanisms controlling FFA release from adipocytes remain undefined. Although obesity promotes systemic inflammation, we find activation of the inflammation-associated Mitogen Activated Protein kinase ERK occurs specifically in adipose tissues of obese mice, and provide evidence that adipocyte ERK activation may explain exaggerated adipose tissue lipolysis observed in obesity...
March 29, 2018: Molecular Metabolism
https://www.readbyqxmd.com/read/29627378/brown-adipose-tissue-derived-angptl4-controls-glucose-and-lipid-metabolism-and-regulates-thermogenesis
#6
Abhishek K Singh, Binod Aryal, Balkrishna Chaube, Noemi Rotllan, Luis Varela, Tamas L Horvath, Yajaira Suárez, Carlos Fernández-Hernando
OBJECTIVES: Brown adipose tissue (BAT) controls triglyceride-rich lipoprotein (TRL) catabolism. This process is mediated by the lipoprotein lipase (LPL), an enzyme that catalyzed the hydrolysis of triglyceride (TAG) in glycerol and fatty acids (FA), which are burned to generate heat. LPL activity is regulated by angiopoietin-like 4 (ANGPTL4), a secretory protein produced in adipose tissues (AT), liver, kidney, and muscle. While the role of ANGPTL4 in regulating lipoprotein metabolism is well established, the specific contribution of BAT derived ANGPTL4 in controlling lipid and glucose homeostasis is not well understood...
March 29, 2018: Molecular Metabolism
https://www.readbyqxmd.com/read/29627377/fgf21-a-liver-hormone-that-inhibits-alcohol-intake-in-mice-increases-in-human-circulation-after-acute-alcohol-ingestion-and-sustained-binge-drinking-at-oktoberfest
#7
Susanna Søberg, Emilie S Andersen, Niels B Dalgaard, Ida Jarlhelt, Nina L Hansen, Nina Hoffmann, Tina Vilsbøll, Anne Chenchar, Michal Jensen, Trisha J Grevengoed, Sam A J Trammell, Filip K Knop, Matthew P Gillum
OBJECTIVE: Excessive alcohol consumption is a leading cause of global morbidity and mortality. However, knowledge of the biological factors that influence ad libitum alcohol intake may be incomplete. Two large studies recently linked variants in the KLB locus with levels of alcohol intake in humans. KLB encodes β-klotho, co-receptor for the liver-derived hormone fibroblast growth factor 21 (FGF21). In mice, FGF21 reduces alcohol intake, and human Fgf21 variants are enriched among heavy drinkers...
March 27, 2018: Molecular Metabolism
https://www.readbyqxmd.com/read/29650351/overexpression-of-st5-an-activator-of-ras-has-no-effect-on-%C3%AE-cell-proliferation-in-adult-mice
#8
Kristy Ou, Jia Zhang, Yang Jiao, Zhao V Wang, Phillipp Scherer, Klaus H Kaestner
OBJECTIVE: Both Type I and Type II diabetes mellitus result from insufficient functional β-cell mass. Efforts to increase β-cell proliferation as a means to restore β-cell mass have been met with limited success. Suppression of Tumorigenicity 5 (ST5) activates Ras/Erk signaling in the presence of Epidermal Growth Factor (EGF). In the pancreatic islet, Ras/Erk signaling is required for augmented β-cell proliferation during pregnancy, suggesting that ST5 is an appealing candidate to enhance adult β-cell proliferation...
March 23, 2018: Molecular Metabolism
https://www.readbyqxmd.com/read/29650350/loss-of-dorsomedial-hypothalamic-glp-1-signaling-reduces-bat-thermogenesis-and-increases-adiposity
#9
Shin J Lee, Graciela Sanchez-Watts, Jean-Philippe Krieger, Angelica Pignalosa, Puck N Norell, Alyssa Cortella, Klaus G Pettersen, Dubravka Vrdoljak, Matthew R Hayes, Scott Kanoski, Wolfgang Langhans, Alan G Watts
OBJECTIVE: Glucagon-like peptide-1 (GLP-1) neurons in the hindbrain densely innervate the dorsomedial hypothalamus (DMH), a nucleus strongly implicated in body weight regulation and the sympathetic control of brown adipose tissue (BAT) thermogenesis. Therefore, DMH GLP-1 receptors (GLP-1R) are well placed to regulate energy balance by controlling sympathetic outflow and BAT function. METHODS: We investigate this possibility in adult male rats by using direct administration of GLP-1 (0...
March 21, 2018: Molecular Metabolism
https://www.readbyqxmd.com/read/29656109/bile-acids-are-important-direct-and-indirect-regulators-of-the-secretion-of-appetite-and-metabolism-regulating-hormones-from-the-gut-and-pancreas
#10
Rune E Kuhre, Nicolai J Wewer Albrechtsen, Olav Larsen, Sara L Jepsen, Emilie Balk-Møller, Daniel B Andersen, Carolyn F Deacon, Kristina Schoonjans, Frank Reimann, Fiona M Gribble, Reidar Albrechtsen, Bolette Hartmann, Mette M Rosenkilde, Jens J Holst
OBJECTIVE: Bile acids (BAs) facilitate fat absorption and may play a role in glucose and metabolism regulation, stimulating the secretion of gut hormones. The relative importance and mechanisms involved in BA-stimulated secretion of appetite and metabolism regulating hormones from the gut and pancreas is not well described and was the purpose of this study. METHODS: The effects of bile acids on the secretion of gut and pancreatic hormones was studied in rats and compared to the most well described nutritional secretagogue: glucose...
March 17, 2018: Molecular Metabolism
https://www.readbyqxmd.com/read/29678421/growth-hormone-receptor-deficient-pigs-resemble-the-pathophysiology-of-human-laron-syndrome-and-reveal-altered-activation-of-signaling-cascades-in-the-liver
#11
Arne Hinrichs, Barbara Kessler, Mayuko Kurome, Andreas Blutke, Elisabeth Kemter, Maren Bernau, Armin M Scholz, Birgit Rathkolb, Simone Renner, Sebastian Bultmann, Heinrich Leonhardt, Martin Hrabĕ de Angelis, Hiroshi Nagashima, Andreas Hoeflich, Werner F Blum, Martin Bidlingmaier, Rüdiger Wanke, Maik Dahlhoff, Eckhard Wolf
OBJECTIVE: Laron syndrome (LS) is a rare, autosomal recessive disorder in humans caused by loss-of-function mutations of the growth hormone receptor (GHR) gene. To establish a large animal model for LS, pigs with GHR knockout (KO) mutations were generated and characterized. METHODS: CRISPR/Cas9 technology was applied to mutate exon 3 of the GHR gene in porcine zygotes. Two heterozygous founder sows with a 1-bp or 7-bp insertion in GHR exon 3 were obtained, and their heterozygous F1 offspring were intercrossed to produce GHR-KO, heterozygous GHR mutant, and wild-type pigs...
March 15, 2018: Molecular Metabolism
https://www.readbyqxmd.com/read/29605715/a-computational-biology-approach-of-a-genome-wide-screen-connected-mirnas-to-obesity-and-type-2-diabetes
#12
Pascal Gottmann, Meriem Ouni, Sophie Sausenthaler, Julian Roos, Laura Stirm, Markus Jähnert, Anne Kamitz, Nicole Hallahan, Wenke Jonas, Andreas Fritsche, Hans-Ulrich Häring, Harald Staiger, Matthias Blüher, Pamela Fischer-Posovszky, Heike Vogel, Annette Schürmann
OBJECTIVE: Obesity and type 2 diabetes (T2D) arise from the interplay between genetic, epigenetic, and environmental factors. The aim of this study was to combine bioinformatics and functional studies to identify miRNAs that contribute to obesity and T2D. METHODS: A computational framework (miR-QTL-Scan) was applied by combining QTL, miRNA prediction, and transcriptomics in order to enhance the power for the discovery of miRNAs as regulative elements. Expression of several miRNAs was analyzed in human adipose tissue and blood cells and miR-31 was manipulated in a human fat cell line...
March 15, 2018: Molecular Metabolism
https://www.readbyqxmd.com/read/29576437/enterochromaffin-5-ht-cells-a-major-target-for-glp-1-and-gut-microbial-metabolites
#13
Mari L Lund, Kristoffer L Egerod, Maja S Engelstoft, Oksana Dmytriyeva, Elvar Theodorsson, Bhavik A Patel, Thue W Schwartz
OBJECTIVES: 5-HT storing enterochromaffin (EC) cells are believed to respond to nutrient and gut microbial components, and 5-HT receptor-expressing afferent vagal neurons have been described to be the major sensors of nutrients in the GI-tract. However, the molecular mechanism through which EC cells sense nutrients and gut microbiota is still unclear. METHODS AND RESULTS: TPH1, the 5-HT generating enzyme, and chromogranin A, an acidic protein responsible for secretory granule storage of 5-HT, were highly enriched in FACS-purified EC cells from both small intestine and colon using a 5-HT antibody-based method...
March 10, 2018: Molecular Metabolism
https://www.readbyqxmd.com/read/29656108/epoxygenase-inactivation-exacerbates-diet-and-aging-associated-metabolic-dysfunction-resulting-from-impaired-adipogenesis
#14
Antoni Olona, Ximena Terra, Jeong-Hun Ko, Carme Grau-Bové, Montserrat Pinent, Anna Ardevol, Ana Garcia Diaz, Aida Moreno-Moral, Matthew Edin, David Bishop-Bailey, Darryl C Zeldin, Timothy J Aitman, Enrico Petretto, Mayte Blay, Jacques Behmoaras
OBJECTIVE: When molecular drivers of healthy adipogenesis are perturbed, this can cause hepatic steatosis. The role of arachidonic acid (AA) and its downstream enzymatic cascades, such as cyclooxygenase, in adipogenesis is well established. The exact contribution of the P450 epoxygenase pathway, however, remains to be established. Enzymes belonging to this pathway are mainly encoded by the CYP2J locus which shows extensive allelic expansion in mice. Here we aimed to establish the role of endogenous epoxygenase during adipogenesis under homeostatic and metabolic stress conditions...
March 9, 2018: Molecular Metabolism
https://www.readbyqxmd.com/read/29551633/an-intracrine-view-of-sex-steroids-immunity-and-metabolic-regulation
#15
REVIEW
Katya B Rubinow
BACKGROUND: Over the past two decades, parallel recognition has grown of the importance of both sex steroids and immune activity in metabolic regulation. More recently, these discrete areas have been integrated in studies examining the metabolic effects of sex steroid immunomodulation. Implicit in these studies has been a traditional, endocrine model of sex steroid delivery from the gonads to target cells, including immune cells. Thus, research to date has focused on the metabolic effects of sex steroid receptor signaling in immune cells...
March 8, 2018: Molecular Metabolism
https://www.readbyqxmd.com/read/29551635/nampt-mediated-nad-biosynthesis-is-indispensable-for-adipose-tissue-plasticity-and-development-of-obesity
#16
Karen Nørgaard Nielsen, Julia Peics, Tao Ma, Iuliia Karavaeva, Morten Dall, Sabina Chubanava, Astrid L Basse, Oksana Dmytriyeva, Jonas T Treebak, Zachary Gerhart-Hines
OBJECTIVE: The ability of adipose tissue to expand and contract in response to fluctuations in nutrient availability is essential for the maintenance of whole-body metabolic homeostasis. Given the nutrient scarcity that mammals faced for millions of years, programs involved in this adipose plasticity were likely evolved to be highly efficient in promoting lipid storage. Ironically, this previously advantageous feature may now represent a metabolic liability given the caloric excess of modern society...
March 7, 2018: Molecular Metabolism
https://www.readbyqxmd.com/read/29551634/adipocyte-xbp1s-overexpression-drives-uridine-production-and-reduces-obesity
#17
Yingfeng Deng, Zhao V Wang, Ruth Gordillo, Yi Zhu, Aktar Ali, Chen Zhang, Xiaoding Wang, Mengle Shao, Zhuzhen Zhang, Puneeth Iyengar, Rana K Gupta, Jay D Horton, Joseph A Hill, Philipp E Scherer
OBJECTIVE: The spliced transcription factor Xbp1 (Xbp1s), a transducer of the unfolded protein response (UPR), regulates lipolysis. Lipolysis is stimulated by fasting when uridine synthesis is also activated in adipocytes. METHODS: Here we have examined the regulatory role Xbp1s in stimulation of uridine biosynthesis in adipocytes and triglyceride mobilization using inducible mouse models. RESULTS: Xbp1s is a key molecule involved in adipocyte uridine biosynthesis and release by activation of carbamoyl-phosphate synthetase 2, aspartate transcarbamylase, dihydroorotase (CAD), the rate-limiting enzyme for UMP biosynthesis...
March 2, 2018: Molecular Metabolism
https://www.readbyqxmd.com/read/29550349/sex-metabolism-and-health
#18
REVIEW
Adriana Maggi, Sara Della Torre
BACKGROUND: Epidemiological and clinical studies have largely demonstrated major differences in the prevalence of metabolic disorders in males and females, but the biological cause of these dissimilarities remain to be elucidated. Mammals are characterized by a major change in reproductive strategies and it is conceivable that these changes subjected females to a significant evolutionary pressure that perfected the coupling between energy metabolism and reproduction. SCOPE OF REVIEW: This review will address the plausibility that female liver functions diverged significantly from males given the role of liver in the control of metabolism...
February 27, 2018: Molecular Metabolism
https://www.readbyqxmd.com/read/29525406/sperm-epigenetics-and-influence-of-environmental-factors
#19
REVIEW
Ida Donkin, Romain Barrès
BACKGROUND: Developmental programming of the embryo is controlled by genetic information but also dictated by epigenetic information contained in spermatozoa. Lifestyle and environmental factors not only influence health in one individual but can also affect the phenotype of the following generations. This is mediated via epigenetic inheritance i.e., gametic transmission of environmentally-driven epigenetic information to the offspring. Evidence is accumulating that preconceptional exposure to certain lifestyle and environmental factors, such as diet, physical activity, and smoking, affects the phenotype of the next generation through remodeling of the epigenetic blueprint of spermatozoa...
February 27, 2018: Molecular Metabolism
https://www.readbyqxmd.com/read/29551636/phosphate-dependent-fgf23-secretion-is-modulated-by-pit2-slc20a2
#20
Nina Bon, Giulia Frangi, Sophie Sourice, Jérôme Guicheux, Sarah Beck-Cormier, Laurent Beck
OBJECTIVE: The canonical role of the bone-derived fibroblast growth factor 23 (Fgf23) is to regulate the serum inorganic phosphate (Pi) level. As part of a feedback loop, serum Pi levels control Fgf23 secretion through undefined mechanisms. We recently showed in vitro that the two high-affinity Na+ -Pi co-transporters PiT1/Slc20a1 and PiT2/Slc20a2 were required for mediating Pi-dependent signaling. Here, we addressed the contribution of PiT1 and PiT2 to the regulation of Fgf23 secretion...
February 26, 2018: Molecular Metabolism
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