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Molecular Metabolism

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https://www.readbyqxmd.com/read/28377876/cannabinoid-type-1-receptor-containing-axons-innervate-npy-agrp-neurons-in-the-mouse-arcuate-nucleus
#1
Yury M Morozov, Marco Koch, Pasko Rakic, Tamas L Horvath
OBJECTIVES: Phytocannabinoids, such as THC and endocannabinoids, are well known to promote feeding behavior and to control energy metabolism through cannabinoid type 1 receptors (CB1R). However, the underlying mechanisms are not fully understood. Generally, cannabinoid-conducted retrograde dis-inhibition of hunger-promoting neurons has been suggested to promote food intake, but so far it has not been demonstrated due to technical limitations. METHODS: We applied immunohistochemical labeling of CB1R for light microscopy and electron microscopy combined with three-dimensional reconstruction from serial sections in CB1R-expressing and CB1R-null mice, which served as a negative control...
April 2017: Molecular Metabolism
https://www.readbyqxmd.com/read/28377875/astrocyte-ikk%C3%AE-nf-%C3%AE%C2%BAb-signaling-is-required-for-diet-induced-obesity-and-hypothalamic-inflammation
#2
J D Douglass, M D Dorfman, R Fasnacht, L D Shaffer, J P Thaler
OBJECTIVE: Obesity and high fat diet (HFD) consumption in rodents is associated with hypothalamic inflammation and reactive gliosis. While neuronal inflammation promotes HFD-induced metabolic dysfunction, the role of astrocyte activation in susceptibility to hypothalamic inflammation and diet-induced obesity (DIO) remains uncertain. METHODS: Metabolic phenotyping, immunohistochemical analyses, and biochemical analyses were performed on HFD-fed mice with a tamoxifen-inducible astrocyte-specific knockout of IKKβ (Gfap(CreER)Ikbkb(fl/fl), IKKβ-AKO), an essential cofactor of NF-κB-mediated inflammation...
April 2017: Molecular Metabolism
https://www.readbyqxmd.com/read/28377874/global-mrna-sequencing-of-human-skeletal-muscle-search-for-novel-exercise-regulated-myokines
#3
S Pourteymour, K Eckardt, T Holen, T Langleite, Sindre Lee, J Jensen, K I Birkeland, C A Drevon, M Hjorth
OBJECTIVE: Skeletal muscle is an important secretory organ, producing and releasing numerous myokines, which may be involved in mediating beneficial health effects of physical activity. More than 100 myokines have been identified by different proteomics approaches, but these techniques may not detect all myokines. We used mRNA sequencing as an untargeted approach to study gene expression of secreted proteins in skeletal muscle upon acute as well as long-term exercise. METHODS: Twenty-six middle-aged, sedentary men underwent combined endurance and strength training for 12 weeks...
April 2017: Molecular Metabolism
https://www.readbyqxmd.com/read/28377873/molecular-phenotyping-of-multiple-mouse-strains-under-metabolic-challenge-uncovers-a-role-for-elovl2-in-glucose-induced-insulin-secretion
#4
Céline Cruciani-Guglielmacci, Lara Bellini, Jessica Denom, Masaya Oshima, Neïké Fernandez, Priscilla Normandie-Levi, Xavier P Berney, Nadim Kassis, Claude Rouch, Julien Dairou, Tracy Gorman, David M Smith, Anna Marley, Robin Liechti, Dmitry Kuznetsov, Leonore Wigger, Frédéric Burdet, Anne-Laure Lefèvre, Isabelle Wehrle, Ingo Uphues, Tobias Hildebrandt, Werner Rust, Catherine Bernard, Alain Ktorza, Guy A Rutter, Raphael Scharfmann, Ioannis Xenarios, Hervé Le Stunff, Bernard Thorens, Christophe Magnan, Mark Ibberson
OBJECTIVE: In type 2 diabetes (T2D), pancreatic β cells become progressively dysfunctional, leading to a decline in insulin secretion over time. In this study, we aimed to identify key genes involved in pancreatic beta cell dysfunction by analyzing multiple mouse strains in parallel under metabolic stress. METHODS: Male mice from six commonly used non-diabetic mouse strains were fed a high fat or regular chow diet for three months. Pancreatic islets were extracted and phenotypic measurements were recorded at 2 days, 10 days, 30 days, and 90 days to assess diabetes progression...
April 2017: Molecular Metabolism
https://www.readbyqxmd.com/read/28377872/dna-methylation-alters-transcriptional-rates-of-differentially-expressed-genes-and-contributes-to-pathophysiology-in-mice-fed-a-high-fat-diet
#5
Pili Zhang, Tianjiao Chu, N Dedousis, Benjamin S Mantell, Ian Sipula, Lucy Li, Kimberly D Bunce, Patricia A Shaw, Liora S Katz, Jun Zhu, Carmen Argmann, Robert M O'Doherty, David G Peters, Donald K Scott
OBJECTIVE: Overnutrition can alter gene expression patterns through epigenetic mechanisms that may persist through generations. However, it is less clear if overnutrition, for example a high fat diet, modifies epigenetic control of gene expression in adults, or by what molecular mechanisms, or if such mechanisms contribute to the pathology of the metabolic syndrome. Here we test the hypothesis that a high fat diet alters hepatic DNA methylation, transcription and gene expression patterns, and explore the contribution of such changes to the pathophysiology of obesity...
April 2017: Molecular Metabolism
https://www.readbyqxmd.com/read/28377871/weight-loss-independent-changes-in-adipose-tissue-macrophage-and-t-cell-populations-after-sleeve-gastrectomy-in-mice
#6
Henriette Frikke-Schmidt, Brian F Zamarron, Robert W O'Rourke, Darleen A Sandoval, Carey N Lumeng, Randy J Seeley
OBJECTIVE: In addition to adipocytes, adipose tissue contains large numbers of immune cells. A wide range of evidence links the activity of these cells to regulation of adipocyte and systemic metabolic function. Bariatric surgery improves several aspects of metabolic derangements and at least some of these effects occur in a weight-loss independent manner. We sought to investigate the impact of vertical sleeve gastrectomy (VSG) on adipose immune cell frequencies. METHODS: We analyzed the frequencies of immune cells within distinct adipose tissue depots in obese mice that had VSG or sham surgery with a portion of the latter group pair-fed such that their body mass was matched to the VSG animals...
April 2017: Molecular Metabolism
https://www.readbyqxmd.com/read/28377870/ampk-is-required-for-exercise-to-enhance-insulin-sensitivity-in-skeletal-muscles
#7
Jørgen Jensen, Stephen O'Rahilly
No abstract text is available yet for this article.
April 2017: Molecular Metabolism
https://www.readbyqxmd.com/read/28377869/response-to-leptin-deficient-mice-are-not-hypothermic-they-are-anapyrexic
#8
Karl J Kaiyala, Kayoko Ogimoto, Jarrell T Nelson, Kenjiro Muta, Gregory J Morton
No abstract text is available yet for this article.
April 2017: Molecular Metabolism
https://www.readbyqxmd.com/read/28271037/cholinergic-neurons-in-the-dorsomedial-hypothalamus-regulate-food-intake
#9
Jae Hoon Jeong, Dong Kun Lee, Young-Hwan Jo
OBJECTIVE: Central cholinergic neural circuits play a role in the regulation of feeding behavior. The dorsomedial hypothalamus (DMH) is considered the appetite-stimulating center and contains cholinergic neurons. Here, we study the role of DMH cholinergic neurons in the control of food intake. METHODS: To selectively stimulate DMH cholinergic neurons, we expressed stimulatory designer receptors exclusively activated by designer drugs (DREADDs) and channelrhodopsins in DMH cholinergic neurons by injection of adeno-associated virus (AAV) vectors into the DMH of choline acetyltransferase (ChAT)-IRES-Cre mice...
March 2017: Molecular Metabolism
https://www.readbyqxmd.com/read/28271036/functional-and-clinical-relevance-of-novel-and-known-pcsk1-variants-for-childhood-obesity-and-glucose-metabolism
#10
Dennis Löffler, Susanne Behrendt, John W M Creemers, Jürgen Klammt, Gabriela Aust, Juraj Stanik, Wieland Kiess, Peter Kovacs, Antje Körner
OBJECTIVE: Variants in Proprotein Convertase Subtilisin/Kexin Type 1 (PCSK1) may be causative for obesity as suggested by monogenic cases and association studies. Here we assessed the functional relevance in experimental studies and the clinical relevance through detailed metabolic phenotyping of newly identified and known PCSK1 variants in children. RESULTS: In 52 obese children selected for elevated proinsulin levels and/or impaired glucose tolerance, we found eight known variants and two novel heterozygous variants (c...
March 2017: Molecular Metabolism
https://www.readbyqxmd.com/read/28271035/attenuated-secretion-of-glucose-dependent-insulinotropic-polypeptide-gip-does-not-alleviate-hyperphagic-obesity-and-insulin-resistance-in-ob-ob-mice
#11
Satoko Shimazu-Kuwahara, Norio Harada, Shunsuke Yamane, Erina Joo, Akiko Sankoda, Timothy J Kieffer, Nobuya Inagaki
OBJECTIVE: Glucose-dependent insulinotropic polypeptide (GIP) is released during meals and promotes nutrient uptake and storage. GIP receptor knockout mice are protected from diet induced weight gain and thus GIP antagonists have been proposed as a treatment for obesity. In this study, we assessed the role of GIP in hyperphagia induced obesity and metabolic abnormalities in leptin deficient (Lep(ob/ob)) mice. METHODS: We crossbred GIP-GFP knock-in homozygous mice (GIP(gfp/gfp)) that have complete GIP knockout, and mice heterozygous for the ob mutation (Lep(ob/+)) mice to generate Lep(ob/+)/GIP(+/+), Lep(ob/ob)/GIP(+/+), and Lep(ob/ob)/GIP(gfp/gfp) mice...
March 2017: Molecular Metabolism
https://www.readbyqxmd.com/read/28271034/divergent-effects-of-a-designer-natriuretic-peptide-cd-np-in-the-regulation-of-adipose-tissue-and-metabolism
#12
Anja Glöde, Jennifer Naumann, Thorsten Gnad, Valentina Cannone, Ana Kilic, John C Burnett, Alexander Pfeifer
OBJECTIVE: Obesity is defined as an abnormal increase in white adipose tissue (WAT) and is a major risk factor for type 2 diabetes and cardiovascular disease. Brown adipose tissue (BAT) dissipates energy and correlates with leanness. Natriuretic peptides have been shown to be beneficial for brown adipocyte differentiation and browning of WAT. METHODS: Here, we investigated the effects of an optimized designer natriuretic peptide (CD-NP) on murine adipose tissues in vitro and in vivo...
March 2017: Molecular Metabolism
https://www.readbyqxmd.com/read/28271033/inducible-overexpression-of-adiponectin-receptors-highlight-the-roles-of-adiponectin-induced-ceramidase-signaling-in-lipid-and-glucose-homeostasis
#13
William L Holland, Jonathan Y Xia, Joshua A Johnson, Kai Sun, Mackenzie J Pearson, Ankit X Sharma, Ezekiel Quittner-Strom, Trevor S Tippetts, Ruth Gordillo, Philipp E Scherer
OBJECTIVE: Adiponectin and the signaling induced by its cognate receptors, AdipoR1 and AdipoR2, have garnered attention for their ability to promote insulin sensitivity and oppose steatosis. Activation of these receptors promotes the deacylation of ceramide, a lipid metabolite that appears to play a causal role in impairing insulin signaling. METHODS: Here, we have developed transgenic mice that overexpress AdipoR1 or AdipoR2 under the inducible control of a tetracycline response element...
March 2017: Molecular Metabolism
https://www.readbyqxmd.com/read/28271032/bezafibrate-ameliorates-diabetes-via-reduced-steatosis-and-improved-hepatic-insulin-sensitivity-in-diabetic-tallyho-mice
#14
Andras Franko, Susanne Neschen, Jan Rozman, Birgit Rathkolb, Michaela Aichler, Annette Feuchtinger, Laura Brachthäuser, Frauke Neff, Marketa Kovarova, Eckhard Wolf, Helmut Fuchs, Hans-Ulrich Häring, Andreas Peter, Martin Hrabě de Angelis
OBJECTIVE: Recently, we have shown that Bezafibrate (BEZ), the pan-PPAR (peroxisome proliferator-activated receptor) activator, ameliorated diabetes in insulin deficient streptozotocin treated diabetic mice. In order to study whether BEZ can also improve glucose metabolism in a mouse model for fatty liver and type 2 diabetes, the drug was applied to TallyHo mice. METHODS: TallyHo mice were divided into an early (ED) and late (LD) diabetes progression group and both groups were treated with 0...
March 2017: Molecular Metabolism
https://www.readbyqxmd.com/read/28271031/enteroendocrine-derived-glucagon-like-peptide-2-controls-intestinal-amino-acid-transport
#15
Jennifer Lee, Jacqueline Koehler, Bernardo Yusta, Jasmine Bahrami, Dianne Matthews, Mahroukh Rafii, Paul B Pencharz, Daniel J Drucker
OBJECTIVE: Glucagon-like peptide-2 (GLP-2) is co-secreted with GLP-1 from gut endocrine cells, and both peptides act as growth factors to expand the surface area of the mucosal epithelium. Notably, GLP-2 also enhances glucose and lipid transport in enterocytes; however, its actions on control of amino acid (AA) transport remain unclear. Here we examined the mechanisms linking gain and loss of GLP-2 receptor (GLP-2R) signaling to control of intestinal amino acid absorption in mice. METHODS: Absorption, transport, and clearance of essential AAs, specifically lysine, were measured in vivo by Liquid Chromatography triple quadrupole Mass Spectrometry (LC-MS/MS) and ex vivo with Ussing chambers using intestinal preparations from Glp2r(+/+) and Glp2r(-/-) mice...
March 2017: Molecular Metabolism
https://www.readbyqxmd.com/read/28271030/high-fidelity-glucagon-creer-mouse-line-generated-by-crispr-cas9-assisted-gene-targeting
#16
Amanda M Ackermann, Jia Zhang, Aryel Heller, Anna Briker, Klaus H Kaestner
OBJECTIVE: α-cells are the second most prominent cell type in pancreatic islets and are responsible for producing glucagon to increase plasma glucose levels in times of fasting. α-cell dysfunction and inappropriate glucagon secretion occur in both type 1 and type 2 diabetes. Thus, there is growing interest in studying both normal function and pathophysiology of α-cells. However, tools to target gene ablation or activation specifically of α-cells have been limited, compared to those available for β-cells...
March 2017: Molecular Metabolism
https://www.readbyqxmd.com/read/28271029/adiponectin-serenades-ceramidase-to-improve-metabolism
#17
Saskia Reibe-Pal, Mark A Febbraio
No abstract text is available yet for this article.
March 2017: Molecular Metabolism
https://www.readbyqxmd.com/read/28180064/dipeptidyl-peptidase-4-inhibitor-treatment-induces-a-greater-increase-in-plasma-levels-of-bioactive-gip-than-glp-1-in-non-diabetic-subjects
#18
Tsuyoshi Yanagimachi, Yukihiro Fujita, Yasutaka Takeda, Jun Honjo, Hidemitsu Sakagami, Hiroya Kitsunai, Yumi Takiyama, Atsuko Abiko, Yuichi Makino, Timothy J Kieffer, Masakazu Haneda
OBJECTIVE: Glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) possess multiple bioactive isoforms that are rendered non-insulinotropic by the enzyme dipeptidyl peptidase-4 (DPP-4). Recently, some ELISA kits have been developed to specifically measure "active" GIP and GLP-1, but it is unclear if these kits can accurately quantify all bioactive forms. Therefore, it remains uncertain to what extent treatment with a DPP-4 inhibitor boosts levels of biologically active GIP and GLP-1...
February 2017: Molecular Metabolism
https://www.readbyqxmd.com/read/28180063/carnitine-acetyltransferase-crat-expression-in-macrophages-is-dispensable-for-nutrient-stress-sensing-and-inflammation
#19
Emily L Goldberg, Vishwa Deep Dixit
OBJECTIVE: Fatty acid oxidation in macrophages is thought to regulate inflammatory status and insulin-sensitivity. An important unanswered question in this field is whether carnitine acetyl-transferase (CrAT) that regulates fatty acid oxidation and mitochondrial acetyl-CoA balance is required to integrate nutrient stress sensing to inflammatory response in macrophages. METHODS: Mice with myeloid lineage-specific Crat deletion were subjected to several metabolic stressors, including high-fat diet-induced obesity, fasting, and LPS-induced endotoxemia...
February 2017: Molecular Metabolism
https://www.readbyqxmd.com/read/28180062/blocking-inos-and-endoplasmic-reticulum-stress-synergistically-improves-insulin-resistance-in-mice
#20
Tamires M Zanotto, Paula G F Quaresma, Dioze Guadagnini, Lais Weissmann, Andressa C Santos, Juliana F Vecina, Kelly Calisto, Andrey Santos, Patrícia O Prada, Mario J A Saad
OBJECTIVE: Recent data show that iNOS has an essential role in ER stress in obesity. However, whether iNOS is sufficient to account for obesity-induced ER stress and Unfolded Protein Response (UPR) has not yet been investigated. In the present study, we used iNOS knockout mice to investigate whether high-fat diet (HFD) can still induce residual ER stress-associated insulin resistance. METHODS: For this purpose, we used the intraperitoneal glucose tolerance test (GTT), euglycemic-hyperinsulinemic clamp, western blotting and qPCR in liver, muscle, and adipose tissue of iNOS KO and control mice on HFD...
February 2017: Molecular Metabolism
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