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Molecular Metabolism

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https://www.readbyqxmd.com/read/28580291/%C3%AE-3-adrenergically-induced-glucose-uptake-in-brown-adipose-tissue-is-independent-of-ucp1-presence-or-activity-mediation-through-the-mtor-pathway
#1
Jessica M Olsen, Robert I Csikasz, Nodi Dehvari, Li Lu, Anna Sandström, Anette I Öberg, Jan Nedergaard, Sharon Stone-Elander, Tore Bengtsson
OBJECTIVE: Today, the presence and activity of brown adipose tissue (BAT) in adult humans is generally equated with the induced accumulation of [2-(18)F]2-fluoro-2-deoxy-d-glucose ([(18)F]FDG) in adipose tissues, as investigated by positron emission tomography (PET) scanning. In reality, PET-FDG is currently the only method available for in vivo quantification of BAT activity in adult humans. The underlying assumption is that the glucose uptake reflects the thermogenic activity of the tissue...
June 2017: Molecular Metabolism
https://www.readbyqxmd.com/read/28580290/fgf21-resistance-is-not-mediated-by-downregulation-of-beta-klotho-expression-in-white-adipose-tissue
#2
Kathleen R Markan, Meghan C Naber, Sarah M Small, Lila Peltekian, Rachel L Kessler, Matthew J Potthoff
OBJECTIVE: Fibroblast growth factor 21 (FGF21) is an endocrine hormone that regulates metabolic homeostasis. Previous work has suggested that impairment of FGF21 signaling in adipose tissue may occur through downregulation of the obligate FGF21 co-receptor, β-klotho, which leads to "FGF21 resistance" during the onset of diet-induced obesity. Here, we sought to determine whether maintenance of β-klotho expression in adipose tissue prevents FGF21 resistance and whether other mechanisms also contribute to FGF21 resistance in vivo...
June 2017: Molecular Metabolism
https://www.readbyqxmd.com/read/28580289/endocannabinoid-dependent-disinhibition-of-orexinergic-neurons-electrophysiological-evidence-in-leptin-knockout-obese-mice
#3
Thorsten Michael Becker, Morgana Favero, Vincenzo Di Marzo, Luigia Cristino, Giuseppe Busetto
OBJECTIVES: In the ob/ob mouse model of obesity, chronic absence of leptin causes a significant increase of orexin (OX) production by hypothalamic neurons and excessive food intake. The altered OX level is linked to a dramatic increase of the inhibitory innervation of OX producing neurons (OX neurons) and the over expression of the endocannabinoid 2-arachidonoylglycerol (2-AG) by OX neurons of ob/ob mice. Little is known about the function of the excitatory synapses of OX neurons in ob/ob mice, and their modulation by 2-AG...
June 2017: Molecular Metabolism
https://www.readbyqxmd.com/read/28580288/restoration-of-lepr-in-%C3%AE-cells-of-lepr-null-mice-does-not-prevent-hyperinsulinemia-and-hyperglycemia
#4
Anna M D'souza, Timothy J Kieffer
OBJECTIVE: The adipose-derived hormone leptin plays an important role in regulating body weight and glucose homeostasis. Leptin receptors are expressed in the central nervous system as well as peripheral tissues involved in regulating glucose homeostasis, including insulin-producing β cells of the pancreas. Previous studies assessing the role of leptin receptors in β cells used Cre-loxP to disrupt the leptin receptor gene (Lepr) in β cells, but variable results were obtained. Furthermore, recombination of Lepr was observed in the hypothalamus or exocrine pancreas, in addition to the β cells, and Lepr in non-β cells may have compensated for the loss of Lepr in β cells, thus making it difficult to assess the direct effects of Lepr in β cells...
June 2017: Molecular Metabolism
https://www.readbyqxmd.com/read/28580287/insulin-controls-food-intake-and-energy-balance-via-npy-neurons
#5
Kim Loh, Lei Zhang, Amanda Brandon, Qiaoping Wang, Denovan Begg, Yue Qi, Melissa Fu, Rishikesh Kulkarni, Jonathan Teo, Paul Baldock, Jens C Brüning, Gregory Cooney, Greg Neely, Herbert Herzog
OBJECTIVES: Insulin signaling in the brain has been implicated in the control of satiety, glucose homeostasis and energy balance. However, insulin signaling is dispensable in energy homeostasis controlling AgRP or POMC neurons and it is unclear which other neurons regulate these effects. Here we describe an ancient insulin/NPY neuronal network that governs energy homeostasis across phyla. METHODS: To address the role of insulin action specifically in NPY neurons, we generated a variety of models by selectively removing insulin signaling in NPY neurons in flies and mice and testing the consequences on energy homeostasis...
June 2017: Molecular Metabolism
https://www.readbyqxmd.com/read/28580286/role-of-nutrients-and-mtor-signaling-in-the-regulation-of-pancreatic-progenitors-development
#6
Lynda Elghazi, Manuel Blandino-Rosano, Emilyn Alejandro, Corentin Cras-Méneur, Ernesto Bernal-Mizrachi
OBJECTIVE: Poor fetal nutrition increases the risk of type 2 diabetes in the offspring at least in part by reduced embryonic β-cell growth and impaired function. However, it is not entirely clear how fetal nutrients and growth factors impact β-cells during development to alter glucose homeostasis and metabolism later in life. The current experiments aimed to test the impact of fetal nutrients and growth factors on endocrine development and how these signals acting on mTOR signaling regulate β-cell mass and glucose homeostasis...
June 2017: Molecular Metabolism
https://www.readbyqxmd.com/read/28580285/opposing-effects-of-prostaglandin-e2-receptors-ep3-and-ep4-on-mouse-and-human-%C3%AE-cell-survival-and-proliferation
#7
Bethany A Carboneau, Jack A Allan, Shannon E Townsend, Michelle E Kimple, Richard M Breyer, Maureen Gannon
OBJECTIVE: Hyperglycemia and systemic inflammation, hallmarks of Type 2 Diabetes (T2D), can induce the production of the inflammatory signaling molecule Prostaglandin E2 (PGE2) in islets. The effects of PGE2 are mediated by its four receptors, E-Prostanoid Receptors 1-4 (EP1-4). EP3 and EP4 play opposing roles in many cell types due to signaling through different G proteins, Gi and GS, respectively. We previously found that EP3 and EP4 expression are reciprocally regulated by activation of the FoxM1 transcription factor, which promotes β-cell proliferation and survival...
June 2017: Molecular Metabolism
https://www.readbyqxmd.com/read/28580284/nnt-reverse-mode-of-operation-mediates-glucose-control-of-mitochondrial-nadph-and-glutathione-redox-state-in-mouse-pancreatic-%C3%AE-cells
#8
Laila R B Santos, Carole Muller, Arnaldo H de Souza, Hilton K Takahashi, Peter Spégel, Ian R Sweet, Heeyoung Chae, Hindrik Mulder, Jean-Christophe Jonas
OBJECTIVE: The glucose stimulation of insulin secretion (GSIS) by pancreatic β-cells critically depends on increased production of metabolic coupling factors, including NADPH. Nicotinamide nucleotide transhydrogenase (NNT) typically produces NADPH at the expense of NADH and ΔpH in energized mitochondria. Its spontaneous inactivation in C57BL/6J mice was previously shown to alter ATP production, Ca(2+) influx, and GSIS, thereby leading to glucose intolerance. Here, we tested the role of NNT in the glucose regulation of mitochondrial NADPH and glutathione redox state and reinvestigated its role in GSIS coupling events in mouse pancreatic islets...
June 2017: Molecular Metabolism
https://www.readbyqxmd.com/read/28580283/foxa2-and-pdx1-cooperatively-regulate-postnatal-maturation-of-pancreatic-%C3%AE-cells
#9
Aimée Bastidas-Ponce, Sara S Roscioni, Ingo Burtscher, Erik Bader, Michael Sterr, Mostafa Bakhti, Heiko Lickert
OBJECTIVE: The transcription factors (TF) Foxa2 and Pdx1 are key regulators of beta-cell (β-cell) development and function. Mutations of these TFs or their respective cis-regulatory consensus binding sites have been linked to maturity diabetes of the young (MODY), pancreas agenesis, or diabetes susceptibility in human. Although Foxa2 has been shown to directly regulate Pdx1 expression during mouse embryonic development, the impact of this gene regulatory interaction on postnatal β-cell maturation remains obscure...
June 2017: Molecular Metabolism
https://www.readbyqxmd.com/read/28580282/hepatic-gene-therapy-rescues-high-fat-diet-responses-in-circadian-clock-mutant-mice
#10
Judit Meyer-Kovac, Isa Kolbe, Lea Ehrhardt, Alexei Leliavski, Jana Husse, Gabriela Salinas, Thomas Lingner, Anthony H Tsang, Johanna L Barclay, Henrik Oster
OBJECTIVE: Circadian Clock gene mutant mice show dampened 24-h feeding rhythms and an increased sensitivity to high-fat diet (HFD) feeding. Restricting HFD access to the dark phase counteracts its obesogenic effect in wild-type mice. The extent to which altered feeding rhythms are causative for the obesogenic phenotype of Clock mutant mice, however, remains unknown. METHODS: Metabolic parameters of wild-type (WT) and Clock(Δ19) mutant mice (MT) were investigated under ad libitum and nighttime restricted HFD feeding...
June 2017: Molecular Metabolism
https://www.readbyqxmd.com/read/28580281/glucagon-like-peptide-2-promotes-gallbladder-refilling-via-a-tgr5-independent-glp-2r-dependent-pathway
#11
Bernardo Yusta, Dianne Matthews, Grace B Flock, John R Ussher, Brigitte Lavoie, Gary M Mawe, Daniel J Drucker
OBJECTIVE: Glucagon-like peptides (GLPs) are secreted from enteroendocrine cells in response to nutrients and bile acids and control metabolism via actions on structurally-related yet distinct G protein coupled receptors. GLP-1 regulates gut motility, appetite, islet function, and glucose homeostasis, whereas GLP-2 enhances intestinal nutrient absorption. GLP-1R agonists are used to treat diabetes and obesity, and a GLP-2R agonist is approved to treat short bowel syndrome. Unexpectedly, reports of gallbladder disease have been associated with the use of both GLP-1R and GLP-2R agonists and after bariatric surgery, although the mechanisms remain unknown...
June 2017: Molecular Metabolism
https://www.readbyqxmd.com/read/28580280/rasal2-deficiency-reduces-adipogenesis-and-occurrence-of-obesity-related-disorders
#12
Xiaoqiang Zhu, Simin Xie, Tian Xu, Xiaohui Wu, Min Han
OBJECTIVE: Identification of additional regulatory factors involved in the onset of obesity is important to understand the mechanisms underlying this prevailing disease and its associated metabolic disorders and to develop therapeutic strategies. Through isolation and analysis of a mutant, we aimed to uncover the function of a Ras-GAP gene, Rasal2 (Ras protein activator like 2), in the development of obesity and related metabolic disorders and to obtain valuable insights regarding the mechanism underlying the function...
June 2017: Molecular Metabolism
https://www.readbyqxmd.com/read/28580279/brown-adipose-tissue-bat-specific-vaspin-expression-is-increased-after-obesogenic-diets-and-cold-exposure-and-linked-to-acute-changes-in-dna-methylation
#13
Juliane Weiner, Kerstin Rohde, Kerstin Krause, Konstanze Zieger, Nora Klöting, Susan Kralisch, Peter Kovacs, Michael Stumvoll, Matthias Blüher, Yvonne Böttcher, John T Heiker
OBJECTIVE: Several studies have demonstrated anti-diabetic and anti-obesogenic properties of visceral adipose tissue-derived serine protease inhibitor (vaspin) and so evoked its potential use for treatment of obesity-related diseases. The aim of the study was to unravel physiological regulators of vaspin expression and secretion with a particular focus on its role in brown adipose tissue (BAT) biology. METHODS: We analyzed the effects of obesogenic diets and cold exposure on vaspin expression in liver and white and brown adipose tissue (AT) and plasma levels...
June 2017: Molecular Metabolism
https://www.readbyqxmd.com/read/28580278/fgf21-does-not-require-adipocyte-amp-activated-protein-kinase-ampk-or-the-phosphorylation-of-acetyl-coa-carboxylase-acc-to-mediate-improvements-in-whole-body-glucose-homeostasis
#14
Emilio P Mottillo, Eric M Desjardins, Andreas M Fritzen, Vito Z Zou, Justin D Crane, Julian M Yabut, Bente Kiens, Derek M Erion, Adhiraj Lanba, James G Granneman, Saswata Talukdar, Gregory R Steinberg
OBJECTIVE: Fibroblast growth factor 21 (FGF21) shows great potential for the treatment of obesity and type 2 diabetes, as its long-acting analogue reduces body weight and improves lipid profiles of participants in clinical studies; however, the intracellular mechanisms mediating these effects are poorly understood. AMP-activated protein kinase (AMPK) is an important energy sensor of the cell and a molecular target for anti-diabetic medications. This work examined the role of AMPK in mediating the glucose and lipid-lowering effects of FGF21...
June 2017: Molecular Metabolism
https://www.readbyqxmd.com/read/28580277/expression-and-functional-assessment-of-candidate-type-2-diabetes-susceptibility-genes-identify-four-new-genes-contributing-to-human-insulin-secretion
#15
Fatou K Ndiaye, Ana Ortalli, Mickaël Canouil, Marlène Huyvaert, Clara Salazar-Cardozo, Cécile Lecoeur, Marie Verbanck, Valérie Pawlowski, Raphaël Boutry, Emmanuelle Durand, Iandry Rabearivelo, Olivier Sand, Lorella Marselli, Julie Kerr-Conte, Vikash Chandra, Raphaël Scharfmann, Odile Poulain-Godefroy, Piero Marchetti, François Pattou, Amar Abderrahmani, Philippe Froguel, Amélie Bonnefond
OBJECTIVES: Genome-wide association studies (GWAS) have identified >100 loci independently contributing to type 2 diabetes (T2D) risk. However, translational implications for precision medicine and for the development of novel treatments have been disappointing, due to poor knowledge of how these loci impact T2D pathophysiology. Here, we aimed to measure the expression of genes located nearby T2D associated signals and to assess their effect on insulin secretion from pancreatic beta cells...
June 2017: Molecular Metabolism
https://www.readbyqxmd.com/read/28462079/loss-of-hepatic-deptor-alters-the-metabolic-transition-to-fasting
#16
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
#17
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
#18
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
#19
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
#20
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
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