TY - JOUR A1 - Seibler, Jost A1 - Küter-Luks, Birgit A1 - Kern, Heidrun A1 - Streu, Sandra A1 - Plum, Leona A1 - Maurer, Jan A1 - Kühn, Ralf A1 - Brüning, Jens C. A1 - Schwenk, Frieder T1 - Single copy shRNA configuration for ubiquitous gene knockdown in mice JF - Nucleic Acids Research Y1 - 2005 U6 - http://dx.doi.org/10.1093/nar/gni065 SN - 1362-4962 VL - 33 IS - 7 SP - e67 ER - TY - JOUR A1 - Plum, Leona A1 - Ma, Xiaosong A1 - Hampel, Brigitte A1 - Balthasar, Nina A1 - Coppari, Roberto A1 - Münzberg, Heike A1 - Shanabrough, Marya A1 - Burdakov, Denis A1 - Rother, Eva A1 - Janoschek, Ruth A1 - Alber, Jens A1 - Belgardt, Bengt F. A1 - Koch, Linda A1 - Seibler, Jost A1 - Schenk, Frieder A1 - Fekete, Csaba A1 - Suzuki, Akira A1 - Mak, Tak W. A1 - Krone, Wilhelm A1 - Horvath, Tamas L. A1 - Ashcroft, Frances M. A1 - Brüning, Jens C. T1 - Enhanced PIP3 signaling in POMC neurons causes KATP channel activation and leads to diet-sensitive obesity JF - The Journal of Clinical Investigation (JCI) Y1 - 2006 U6 - http://dx.doi.org/10.1172/JCI27123 SN - 1558-8238 VL - 116 IS - 7 SP - 1886 EP - 1901 ER - TY - JOUR A1 - Seibler, Jost A1 - Kleinridders, Andre A1 - Küter-Luks, Birgit A1 - Niehaves, Sandra A1 - Brüning, Jens C. A1 - Schwenk, Frieder T1 - Reversible gene knockdown in mice using a tight, inducible shRNA expression system JF - Nucleic Acids Research Y1 - 2007 U6 - http://dx.doi.org/10.1093/nar/gkm122 SN - 1362-4962 VL - 35 IS - 7 SP - e54 ER - TY - JOUR A1 - Koch, Linda A1 - Wunderlich, F. Thomas A1 - Seibler, Jost A1 - Könner, A. Christine A1 - Hampel, Brigitte A1 - Irlenbusch, Sigrid A1 - Brabant, Georg A1 - Kahn, C. Ronald A1 - Schwenk, Frieder A1 - Brüning, Jens C. T1 - Central insulin action regulates peripheral glucose and fat metabolism in mice JF - The Journal of Clinical Investigation (JCI) Y1 - 2008 U6 - http://dx.doi.org/10.1172/JCI31073 SN - 1558-8238 VL - 118 IS - 6 SP - 2132 EP - 2147 ER - TY - JOUR A1 - Jordan, Sabine D. A1 - Krüger, Markus A1 - Willmes, Diana M. A1 - Redemann, Nora A1 - Wunderlich, F. Thomas A1 - Brönneke, Hella S. A1 - Merkwirth, Carsten A1 - Kashkar, Hamid A1 - Olkkonen, Vesa M. A1 - Böttger, Thomas A1 - Braun, Thomas A1 - Seibler, Jost A1 - Brüning, Jens C. T1 - Obesity-induced overexpression of miRNA-143 inhibits insulin-stimulated AKT activation and impairs glucose metabolism JF - Nature Cell Biology N2 - The contribution of altered post-transcriptional gene silencing to the development of insulin resistance and type 2 diabetes mellitus so far remains elusive. Here, we demonstrate that expression of microRNA (miR)-143 and 145 is upregulated in the liver of genetic and dietary mouse models of obesity. Induced transgenic overexpression of miR-143, but not miR-145, impairs insulin-stimulated AKT activation and glucose homeostasis. Conversely, mice deficient for the miR-143–145 cluster are protected from the development of obesity-associated insulin resistance. Quantitative-mass-spectrometry-based analysis of hepatic protein expression in miR-143-overexpressing mice revealed miR-143-dependent downregulation of oxysterol-binding-protein-related protein (ORP) 8. Reduced ORP8 expression in cultured liver cells impairs the ability of insulin to induce AKT activation, revealing an ORP8-dependent mechanism of AKT regulation. Our experiments provide direct evidence that dysregulated post-transcriptional gene silencing contributes to the development of obesity-induced insulin resistance, and characterize the miR-143–ORP8 pathway as a potential target for the treatment of obesity-associated diabetes. Y1 - 2011 U6 - http://dx.doi.org/10.1038/ncb2211 SN - 1465-7392 VL - 13 IS - 4 SP - 434 EP - 446 PB - Nature CY - New York ER - TY - JOUR A1 - Kornfeld, Jan-Wilhelm A1 - Baitzel, Catherina A1 - Könner, A. Christine A1 - Nicholls, Hayley T. A1 - Vogt, Merly C. A1 - Herrmanns, Karolin A1 - Scheja, Ludger A1 - Haumaitre, Cécile A1 - Wolf, Anna M. A1 - Knippschild, Uwe A1 - Seibler, Jost A1 - Cereghini, Silvia A1 - Heeren, Joerg A1 - Stoffel, Markus A1 - Brüning, Jens C. T1 - Obesity-induced overexpression of miR-802 impairs glucose metabolism through silencing of Hnf1b JF - Nature Y1 - 2013 SN - 0028-0836 U6 - http://dx.doi.org/10.1038/nature11793 VL - 494 IS - 7435 SP - 111 EP - 115 PB - Springer Nature CY - Cham ER -