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Molecular Metabolism

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https://www.readbyqxmd.com/read/28462079/loss-of-hepatic-deptor-alters-the-metabolic-transition-to-fasting
#1
Alexandre Caron, Mathilde Mouchiroud, Nicolas Gautier, Sébastien M Labbé, Romain Villot, Laurie Turcotte, Blandine Secco, Guillaume Lamoureux, Michael Shum, Yves Gélinas, André Marette, Denis Richard, David M Sabatini, Mathieu Laplante
OBJECTIVE: The mechanistic target of rapamycin (mTOR) is a serine/threonine kinase that functions into distinct protein complexes (mTORC1 and mTORC2) that regulates growth and metabolism. DEP-domain containing mTOR-interacting protein (DEPTOR) is part of these complexes and is known to reduce their activity. Whether DEPTOR loss affects metabolism and organismal growth in vivo has never been tested. METHODS: We have generated a conditional transgenic mouse allowing the tissue-specific deletion of DEPTOR...
May 2017: Molecular Metabolism
https://www.readbyqxmd.com/read/28462078/monomeric-glp-1-gip-glucagon-triagonism-corrects-obesity-hepatosteatosis-and-dyslipidemia-in-female-mice
#2
Sigrid Jall, Stephan Sachs, Christoffer Clemmensen, Brian Finan, Frauke Neff, Richard D DiMarchi, Matthias H Tschöp, Timo D Müller, Susanna M Hofmann
OBJECTIVE: Obesity is a major health threat that affects men and women equally. Despite this fact, weight-loss potential of pharmacotherapies is typically first evaluated in male mouse models of diet-induced obesity (DIO). To address this disparity we herein determined whether a monomeric peptide with agonism at the receptors for glucagon-like peptide 1 (GLP-1), glucose-dependent insulinotropic polypeptide (GIP), and glucagon is equally efficient in correcting DIO, dyslipidemia, and glucose metabolism in DIO female mice as it has been previously established for DIO male mice...
May 2017: Molecular Metabolism
https://www.readbyqxmd.com/read/28462077/pdk1-foxo1-pathway-in-agrp-neurons-of-arcuate-nucleus-promotes-bone-formation-via-ghrh-gh-igf1-axis
#3
Hideyuki Sasanuma, Masanori Nakata, Kumari Parmila, Jun Nakae, Toshihiko Yada
OBJECTIVE: In the hypothalamic arcuate nucleus (ARC), orexigenic agouti-related peptide (AgRP) neurons regulate feeding behavior and energy homeostasis, functions connected to bone metabolism. The 3-phosphoinositide-dependent protein kinase-1 (PDK1) serves as a major signaling molecule particularly for leptin and insulin in AgRP neurons. We asked whether PDK1 in AGRP neurons also contributes to bone metabolism. METHODS: We generated AgRP neuron-specific PDK1 knockout (Agrp Pdk1(-/-) ) mice and those with additional AgRP neuron-specific expression of transactivation-defective FoxO1 (Agrp Pdk1(-/-)Δ256Foxo1)...
May 2017: Molecular Metabolism
https://www.readbyqxmd.com/read/28462076/acid-sphingomyelinase-deficiency-in-western-diet-fed-mice-protects-against-adipocyte-hypertrophy-and-diet-induced-liver-steatosis
#4
Svenja Sydor, Jan-Peter Sowa, Dominik A Megger, Martin Schlattjan, Sami Jafoui, Lena Wingerter, Alexander Carpinteiro, Hideo A Baba, Lars P Bechmann, Barbara Sitek, Guido Gerken, Erich Gulbins, Ali Canbay
OBJECTIVE: Alterations in sphingolipid and ceramide metabolism have been associated with various diseases, including nonalcoholic fatty liver disease (NAFLD). Acid sphingomyelinase (ASM) converts the membrane lipid sphingomyelin to ceramide, thereby affecting membrane composition and domain formation. We investigated the ways in which the Asm knockout (Smpd1(-/-)) genotype affects diet-induced NAFLD. METHODS: Smpd1(-/-) mice and wild type controls were fed either a standard or Western diet (WD) for 6 weeks...
May 2017: Molecular Metabolism
https://www.readbyqxmd.com/read/28462075/plasma-2-arachidonoylglycerol-is-a-biomarker-of-age-and-menopause-related-insulin-resistance-and-dyslipidemia-in-lean-but-not-in-obese-men-and-women
#5
Flaminia Fanelli, Marco Mezzullo, Ilaria Belluomo, Valentina Diana Di Lallo, Margherita Baccini, Daniela Ibarra Gasparini, Elena Casadio, Marianna Mastroroberto, Valentina Vicennati, Alessandra Gambineri, Antonio Maria Morselli-Labate, Renato Pasquali, Uberto Pagotto
OBJECTIVE: The endocannabinoid system hypertonicity features obesity. Excess circulating 2-arachidonoylglycerol was variously associated with obesity-related metabolic impairment; however, unstandardized experimental and analytical settings have clouded its usefulness as a dysmetabolism biomarker. We aimed at assessing the influence of body mass index (BMI), menopause in women, and aging in men on 2-arachidonoylglycerol relationship with metabolic parameters. METHODS: Adult, unmedicated women (premenopausal (preMW): n = 103; menopausal (MW): n = 81) and men (n = 144) were stratified in normal weight (NW; BMI: 18...
May 2017: Molecular Metabolism
https://www.readbyqxmd.com/read/28462074/hypothalamic-growth-hormone-receptor-ghr-%C3%A2-controls-hepatic-glucose-production-in-nutrient-sensing-leptin-receptor-leprb-expressing-neurons
#6
Gillian Cady, Taylor Landeryou, Michael Garratt, John J Kopchick, Nathan Qi, David Garcia-Galiano, Carol F Elias, Martin G Myers, Richard A Miller, Darleen A Sandoval, Marianna Sadagurski
OBJECTIVE: The GH/IGF-1 axis has important roles in growth and metabolism. GH and GH receptor (GHR) are active in the central nervous system (CNS) and are crucial in regulating several aspects of metabolism. In the hypothalamus, there is a high abundance of GH-responsive cells, but the role of GH signaling in hypothalamic neurons is unknown. Previous work has demonstrated that the Ghr gene is highly expressed in LepRb neurons. Given that leptin is a key regulator of energy balance by acting on leptin receptor (LepRb)-expressing neurons, we tested the hypothesis that LepRb neurons represent an important site for GHR signaling to control body homeostasis...
May 2017: Molecular Metabolism
https://www.readbyqxmd.com/read/28462073/heterogeneity-of-hypothalamic-pro-opiomelanocortin-expressing-neurons-revealed-by-single-cell-rna-sequencing
#7
Brian Y H Lam, Irene Cimino, Joseph Polex-Wolf, Sara Nicole Kohnke, Debra Rimmington, Valentine Iyemere, Nicholas Heeley, Chiara Cossetti, Reiner Schulte, Luis R Saraiva, Darren W Logan, Clemence Blouet, Stephen O'Rahilly, Anthony P Coll, Giles S H Yeo
OBJECTIVE: Arcuate proopiomelanocortin (POMC) neurons are critical nodes in the control of body weight. Often characterized simply as direct targets for leptin, recent data suggest a more complex architecture. METHODS: Using single cell RNA sequencing, we have generated an atlas of gene expression in murine POMC neurons. RESULTS: Of 163 neurons, 118 expressed high levels of Pomc with little/no Agrp expression and were considered "canonical" POMC neurons (P(+))...
May 2017: Molecular Metabolism
https://www.readbyqxmd.com/read/28377876/cannabinoid-type-1-receptor-containing-axons-innervate-npy-agrp-neurons-in-the-mouse-arcuate-nucleus
#8
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
#9
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
#10
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
#11
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
#12
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
#13
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
#14
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
#15
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
#16
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
#17
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
#18
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
#19
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
#20
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
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