Buchumschlag

MicroRNA‐379 couples glucocorticoid hormones to dysfunctional lipid homeostasis

In mammals, glucocorticoids (GCs) and their intracellular receptor, the glucocorticoid receptor (GR), represent critical checkpoints in the endocrine control of energy homeostasis. Indeed, aberrant GC action is linked to severe metabolic stress conditions as seen in Cushing's syndrome, GC thera...

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Hauptverfasser: Guia, Roldan M. de (Verfasst von) , Rose, Adam J. (Verfasst von) , Seibert, Oksana (Verfasst von) , Strzoda, Daniela (Verfasst von) , Zota, Annika (Verfasst von) , Feuchter, Yvonne (Verfasst von) , Krones-Herzig, Anja (Verfasst von) , Kirilov, Milen (Verfasst von) , Sticht, Carsten (Verfasst von) , Gretz, Norbert (Verfasst von) , Diederichs, Sven (Verfasst von) , Berriel Diaz, Mauricio (Verfasst von) , Herzig, Stephan (Verfasst von)
Dokumenttyp: Article (Journal)
Sprache:Englisch
Veröffentlicht: 2015
In: The EMBO journal
Year: 2014, Jahrgang: 34, Heft: 3, Pages: 344-360
ISSN:1460-2075
DOI:10.15252/embj.201490464
Online-Zugang:Verlag, teilw. kostenfrei, Volltext: http://dx.doi.org/10.15252/embj.201490464
Verlag, teilw. kostenfrei, Volltext: http://emboj.embopress.org/content/34/3/344
Volltext
Verfasserangaben:Roldan M. de Guia, Adam J. Rose, Anke Sommerfeld, Oksana Seibert, Daniela Strzoda, Annika Zota, Yvonne Feuchter, Anja Krones‐Herzig, Tjeerd Sijmonsma, Milen Kirilov, Carsten Sticht, Norbert Gretz, Geesje Dallinga‐Thie, Sven Diederichs, Nora Klöting, Matthias Blüher, Mauricio Berriel Diaz and Stephan Herzig
Beschreibung
Zusammenfassung:In mammals, glucocorticoids (GCs) and their intracellular receptor, the glucocorticoid receptor (GR), represent critical checkpoints in the endocrine control of energy homeostasis. Indeed, aberrant GC action is linked to severe metabolic stress conditions as seen in Cushing's syndrome, GC therapy and certain components of the Metabolic Syndrome, including obesity and insulin resistance. Here, we identify the hepatic induction of the mammalian conserved microRNA (miR)‐379/410 genomic cluster as a key component of GC/GR‐driven metabolic dysfunction. Particularly, miR‐379 was up‐regulated in mouse models of hyperglucocorticoidemia and obesity as well as human liver in a GC/GR‐dependent manner. Hepatocyte‐specific silencing of miR‐379 substantially reduced circulating very‐low‐density lipoprotein (VLDL)‐associated triglyceride (TG) levels in healthy mice and normalized aberrant lipid profiles in metabolically challenged animals, mediated through miR‐379 effects on key receptors in hepatic TG re‐uptake. As hepatic miR‐379 levels were also correlated with GC and TG levels in human obese patients, the identification of a GC/GR‐controlled miRNA cluster not only defines a novel layer of hormone‐dependent metabolic control but also paves the way to alternative miRNA‐based therapeutic approaches in metabolic dysfunction.
Beschreibung:Published online: December 15, 2014
Gesehen am 29.08.2017
Beschreibung:Online Resource
ISSN:1460-2075
DOI:10.15252/embj.201490464

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