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micro RNA ‐379 couples glucocorticoid hormones to dysfunctional lipid homeostasis
Author(s) -
Guia Roldan M,
Rose Adam J,
Sommerfeld Anke,
Seibert Oksana,
Strzoda Daniela,
Zota Annika,
Feuchter Yvonne,
KronesHerzig Anja,
Sijmonsma Tjeerd,
Kirilov Milen,
Sticht Carsten,
Gretz Norbert,
DallingaThie Geesje,
Diederichs Sven,
Klöting Nora,
Blüher Matthias,
Berriel Diaz Mauricio,
Herzig Stephan
Publication year - 2014
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.15252/embj.201490464
Subject(s) - biology , dysfunctional family , hormone , glucocorticoid , homeostasis , microbiology and biotechnology , endocrinology , psychology , psychotherapist
In mammals, glucocorticoids ( GC s) 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 micro RNA (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 mi RNA cluster not only defines a novel layer of hormone‐dependent metabolic control but also paves the way to alternative mi RNA ‐based therapeutic approaches in metabolic dysfunction.