TY  - JOUR
A1  - Hesse, Deike
A1  - Jaschke, Alexander
A1  - Kanzleiter, Timo
A1  - Witte, Nicole
A1  - Augustin, Robert
A1  - Hommel, Angela
A1  - Püschel, Gerhard Paul
A1  - Petzke, Klaus-Jürgen
A1  - Joost, Hans-Georg
A1  - Schupp, Michael
A1  - Schürmann, Annette
T1  - GTPase ARFRP1 is essential for normal hepatic glycogen storage and insulin-like growth factor 1 secretion
JF  - Molecular and cellular biology
N2  - The GTPase ADP-ribosylation factor-related protein 1 (ARFRP1) is located at the trans-Golgi compartment and regulates the recruitment of Arf-like 1 (ARL1) and its effector golgin-245 to this compartment. Here, we show that liver-specific knockout of Arfrp1 in the mouse (Arfrp1(liv-/-)) resulted in early growth retardation, which was associated with reduced hepatic insulin-like growth factor 1 (IGF1) secretion. Accordingly, suppression of Arfrp1 in primary hepatocytes resulted in a significant reduction of IGF1 release. However, the hepatic secretion of IGF-binding protein 2 (IGFBP2) was not affected in the absence of ARFRP1. In addition, Arfrp1(liv-/-) mice exhibited decreased glucose transport into the liver, leading to a 50% reduction of glycogen stores as well as a marked retardation of glycogen storage after fasting and refeeding. These abnormalities in glucose metabolism were attributable to reduced protein levels and intracellular retention of the glucose transporter GLUT2 in Arfrp1(liv-/-) livers. As a consequence of impaired glucose uptake into the liver, the expression levels of carbohydrate response element binding protein (ChREBP), a transcription factor regulated by glucose concentration, and its target genes (glucokinase and pyruvate kinase) were markedly reduced. Our data indicate that ARFRP1 in the liver is involved in the regulation of IGF1 secretion and GLUT2 sorting and is thereby essential for normal growth and glycogen storage.
Y1  - 2012
U6  - https://doi.org/10.1128/MCB.00522-12
SN  - 0270-7306
VL  - 32
IS  - 21
SP  - 4363
EP  - 4374
PB  - American Society for Microbiology
CY  - Washington
ER  - 
TY  - JOUR
A1  - Münzner, Matthias
A1  - Tuvia, Neta
A1  - Deutschmann, Claudia
A1  - Witte, Nicole
A1  - Tolkachov, Alexander
A1  - Valai, Atijeh
A1  - Henze, Andrea
A1  - Sander, Leif E.
A1  - Raila, Jens
A1  - Schupp, Michael
T1  - Retinol-binding protein 4 and its membrane receptor STRA6 control adipogenesis by regulating cellular retinoid homeostasis and retinoic acid receptor alpha activity
JF  - Molecular and cellular biology
N2  - Retinoids are vitamin A (retinol) derivatives and complex regulators of adipogenesis by activating specific nuclear receptors, including the retinoic acid receptor (RAR) and retinoid X receptor (RXR). Circulating retinol-binding protein 4 (RBP4) and its membrane receptor STRA6 coordinate cellular retinol uptake. It is unknown whether retinol levels and the activity of RAR and RXR in adipocyte precursors are linked via RBP4/STRA6. Here, we show that STRA6 is expressed in precursor cells and, dictated by the apo-and holo-RBP4 isoforms, mediates bidirectional retinol transport that controls RAR alpha activity and subsequent adipocyte differentiation. Mobilization of retinoid stores in mice by inducing RBP4 secretion from the liver activated RAR alpha signaling in the precursor cell containing the stromal-vascular fraction of adipose tissue. Retinol-loaded holo-RBP4 blocked adipocyte differentiation of cultured precursors by activating RAR alpha. Remarkably, retinol-free apo-RBP4 triggered retinol efflux that reduced cellular retinoids, RAR alpha activity, and target gene expression and enhanced adipogenesis synergistically with ectopic STRA6. Thus, STRA6 in adipocyte precursor cells links nuclear RAR alpha activity to the circulating RBP4 isoforms, whose ratio in obese mice was shifted toward limiting the adipogenic potential of their precursors. This novel cross talk identifies a retinoldependent metabolic function of RBP4 that may have important implications for the treatment of obesity.
Y1  - 2013
U6  - https://doi.org/10.1128/MCB.00221-13
SN  - 0270-7306
SN  - 1098-5549
VL  - 33
IS  - 20
SP  - 4068
EP  - 4082
PB  - American Society for Microbiology
CY  - Washington
ER  - 
TY  - JOUR
A1  - Horikoshi, Momoko
A1  - Yaghootkar, Hanieh
A1  - Mook-Kanamori, Dennis O.
A1  - Sovio, Ulla
A1  - Taal, H. Rob
A1  - Hennig, Branwen J.
A1  - Bradfield, Jonathan P.
A1  - St Pourcain, Beate
A1  - Evans, David M.
A1  - Charoen, Pimphen
A1  - Kaakinen, Marika
A1  - Cousminer, Diana L.
A1  - Lehtimaki, Terho
A1  - Kreiner-Moller, Eskil
A1  - Warrington, Nicole M.
A1  - Bustamante, Mariona
A1  - Feenstra, Bjarke
A1  - Berry, Diane J.
A1  - Thiering, Elisabeth
A1  - Pfab, Thiemo
A1  - Barton, Sheila J.
A1  - Shields, Beverley M.
A1  - Kerkhof, Marjan
A1  - van Leeuwen, Elisabeth M.
A1  - Fulford, Anthony J.
A1  - Kutalik, Zoltan
A1  - Zhao, Jing Hua
A1  - den Hoed, Marcel
A1  - Mahajan, Anubha
A1  - Lindi, Virpi
A1  - Goh, Liang-Kee
A1  - Hottenga, Jouke-Jan
A1  - Wu, Ying
A1  - Raitakari, Olli T.
A1  - Harder, Marie N.
A1  - Meirhaeghe, Aline
A1  - Ntalla, Ioanna
A1  - Salem, Rany M.
A1  - Jameson, Karen A.
A1  - Zhou, Kaixin
A1  - Monies, Dorota M.
A1  - Lagou, Vasiliki
A1  - Kirin, Mirna
A1  - Heikkinen, Jani
A1  - Adair, Linda S.
A1  - Alkuraya, Fowzan S.
A1  - Al-Odaib, Ali
A1  - Amouyel, Philippe
A1  - Andersson, Ehm Astrid
A1  - Bennett, Amanda J.
A1  - Blakemore, Alexandra I. F.
A1  - Buxton, Jessica L.
A1  - Dallongeville, Jean
A1  - Das, Shikta
A1  - de Geus, Eco J. C.
A1  - Estivill, Xavier
A1  - Flexeder, Claudia
A1  - Froguel, Philippe
A1  - Geller, Frank
A1  - Godfrey, Keith M.
A1  - Gottrand, Frederic
A1  - Groves, Christopher J.
A1  - Hansen, Torben
A1  - Hirschhorn, Joel N.
A1  - Hofman, Albert
A1  - Hollegaard, Mads V.
A1  - Hougaard, David M.
A1  - Hyppoenen, Elina
A1  - Inskip, Hazel M.
A1  - Isaacs, Aaron
A1  - Jorgensen, Torben
A1  - Kanaka-Gantenbein, Christina
A1  - Kemp, John P.
A1  - Kiess, Wieland
A1  - Kilpelainen, Tuomas O.
A1  - Klopp, Norman
A1  - Knight, Bridget A.
A1  - Kuzawa, Christopher W.
A1  - McMahon, George
A1  - Newnham, John P.
A1  - Niinikoski, Harri
A1  - Oostra, Ben A.
A1  - Pedersen, Louise
A1  - Postma, Dirkje S.
A1  - Ring, Susan M.
A1  - Rivadeneira, Fernando
A1  - Robertson, Neil R.
A1  - Sebert, Sylvain
A1  - Simell, Olli
A1  - Slowinski, Torsten
A1  - Tiesler, Carla M. T.
A1  - Toenjes, Anke
A1  - Vaag, Allan
A1  - Viikari, Jorma S.
A1  - Vink, Jacqueline M.
A1  - Vissing, Nadja Hawwa
A1  - Wareham, Nicholas J.
A1  - Willemsen, Gonneke
A1  - Witte, Daniel R.
A1  - Zhang, Haitao
A1  - Zhao, Jianhua
A1  - Wilson, James F.
A1  - Stumvoll, Michael
A1  - Prentice, Andrew M.
A1  - Meyer, Brian F.
A1  - Pearson, Ewan R.
A1  - Boreham, Colin A. G.
A1  - Cooper, Cyrus
A1  - Gillman, Matthew W.
A1  - Dedoussis, George V.
A1  - Moreno, Luis A.
A1  - Pedersen, Oluf
A1  - Saarinen, Maiju
A1  - Mohlke, Karen L.
A1  - Boomsma, Dorret I.
A1  - Saw, Seang-Mei
A1  - Lakka, Timo A.
A1  - Koerner, Antje
A1  - Loos, Ruth J. F.
A1  - Ong, Ken K.
A1  - Vollenweider, Peter
A1  - van Duijn, Cornelia M.
A1  - Koppelman, Gerard H.
A1  - Hattersley, Andrew T.
A1  - Holloway, John W.
A1  - Hocher, Berthold
A1  - Heinrich, Joachim
A1  - Power, Chris
A1  - Melbye, Mads
A1  - Guxens, Monica
A1  - Pennell, Craig E.
A1  - Bonnelykke, Klaus
A1  - Bisgaard, Hans
A1  - Eriksson, Johan G.
A1  - Widen, Elisabeth
A1  - Hakonarson, Hakon
A1  - Uitterlinden, Andre G.
A1  - Pouta, Anneli
A1  - Lawlor, Debbie A.
A1  - Smith, George Davey
A1  - Frayling, Timothy M.
A1  - McCarthy, Mark I.
A1  - Grant, Struan F. A.
A1  - Jaddoe, Vincent W. V.
A1  - Jarvelin, Marjo-Riitta
A1  - Timpson, Nicholas J.
A1  - Prokopenko, Inga
A1  - Freathy, Rachel M.
T1  - New loci associated with birth weight identify genetic links between intrauterine growth and adult height and metabolism
JF  - Nature genetics
N2  - Birth weight within the normal range is associated with a variety of adult-onset diseases, but the mechanisms behind these associations are poorly understood(1). Previous genome-wide association studies of birth weight identified a variant in the ADCY5 gene associated both with birth weight and type 2 diabetes and a second variant, near CCNL1, with no obvious link to adult traits(2). In an expanded genome-wide association metaanalysis and follow-up study of birth weight (of up to 69,308 individuals of European descent from 43 studies), we have now extended the number of loci associated at genome-wide significance to 7, accounting for a similar proportion of variance as maternal smoking. Five of the loci are known to be associated with other phenotypes: ADCY5 and CDKAL1 with type 2 diabetes, ADRB1 with adult blood pressure and HMGA2 and LCORL with adult height. Our findings highlight genetic links between fetal growth and postnatal growth and metabolism.
Y1  - 2013
U6  - https://doi.org/10.1038/ng.2477
SN  - 1061-4036
VL  - 45
IS  - 1
SP  - 76
EP  - U115
PB  - Nature Publ. Group
CY  - New York
ER  -