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Mueller, K.M.* ; Hartmann, K.* ; Kaltenecker, D.* ; Vettorazzi, S.* ; Bauer, M.* ; Mauser, L.* ; Amann, S.* ; Jall, S. ; Fischer, K. ; Esterbauer, H.* ; Müller, T.D. ; Tschöp, M.H. ; Magnes, C.* ; Haybaeck, J.* ; Scherer, T.* ; Bordag, N.* ; Tuckermann, J.P.* ; Moriggl, R.*

Adipocyte glucocorticoid receptor deficiency attenuates aging and HFDinduced obesity, and impairs the feedingfasting transition.

Diabetes 66, 272-286:db160381 (2016)
Verlagsversion Postprint Forschungsdaten DOI
Open Access Green
Glucocorticoids (GCs) are important regulators of systemic energy metabolism, while aberrant GC action is linked to metabolic dysfunctions. Yet, the extent to which normal and pathophysiologic energy metabolism depend on the glucocorticoid receptor (GR) in adipocytes remains unclear. Here, we demonstrate that adipocyte GR-deficiency in mice significantly impacts systemic metabolism in different energetic states. Plasma metabolomics and biochemical analyses revealed a marked global effect of GR-deficiency on systemic metabolite abundance and thus, substrate partitioning in fed and fasted states. This correlated with a decreased lipolytic capacity of GR-deficient adipocytes under post-absorptive and fasting conditions, resulting from impaired signal transduction from β-adrenergic receptors to adenylate cyclase. Upon prolonged fasting, the impaired lipolytic response resulted in abnormal substrate utilization and lean mass wasting. Conversely, GR-deficiency attenuated aging-/diet-associated obesity, adipocyte hypertrophy and liver steatosis. Systemic glucose tolerance was improved in obese GR-deficient mice, which was associated with increased insulin signaling in muscle and adipose tissue.We conclude that the GR in adipocytes exerts central, but diverging roles in the regulation of metabolic homeostasis depending on the energetic state: The adipocyte GR is indispensable for the feeding-fasting transition, but also promotes adiposity and associated metabolic disorders in fat-fed and aged mice.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Schlagwörter Glucocorticoids, adipose tissue, energy metabolism, fasting, obesity; Adipose-tissue Lipolysis; Diet-induced Obesity; Switch Gene 2; Insulin-resistance; Energy-metabolism; Lipid-metabolism; Mass-spectrometry; Visceral Obesity; Cycle Function; Fatty Liver
ISSN (print) / ISBN 0012-1797
e-ISSN 1939-327X
Zeitschrift Diabetes
Quellenangaben Band: 66, Heft: 2, Seiten: 272-286, Artikelnummer: db160381 Supplement: ,
Verlag American Diabetes Association
Verlagsort Alexandria, VA.
Begutachtungsstatus Peer reviewed