Medizinische Universität Graz - Research portal
Selected Publication:
SHR Neuro Cancer Cardio Lipid Metab Microb
Mueller, KM; Hartmann, K; Kaltenecker, D; Vettorazzi, S; Bauer, M; Mauser, L; Amann, S; Jall, S; Fischer, K; Esterbauer, H; Müller, TD; Tschöp, MH; Magnes, C; Haybaeck, J; Scherer, T; Bordag, N; Tuckermann, JP; Moriggl, R.
Adipocyte Glucocorticoid Receptor Deficiency Attenuates Aging- and HFD-Induced Obesity and Impairs the Feeding-Fasting Transition.
Diabetes. 2017; 66(2):272-286
Doi: 10.2337/db16-0381
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- Co-authors Med Uni Graz
- Bordag Natalie
- Haybäck Johannes
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- Abstract:
- Glucocorticoids (GCs) are important regulators of systemic energy metabolism, and aberrant GC action is linked to metabolic dysfunctions. Yet, the extent to which normal and pathophysiological energy metabolism depend on the GC 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 postabsorptive 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. © 2017 by the American Diabetes Association.
- Find related publications in this database (using NLM MeSH Indexing)
- Adenylyl Cyclases - metabolism
- Adipocytes - metabolism
- Adipose Tissue - metabolism
- Adiposity - genetics
- Aging - genetics
- Aging - metabolism
- Animals -
- Blotting, Western -
- Chromatography, Liquid -
- Diet, High-Fat -
- Energy Metabolism -
- Fasting -
- Fatty Liver - genetics
- Feeding Behavior -
- Hypertrophy -
- Insulin - metabolism
- Lipid Metabolism - genetics
- Lipolysis -
- Liver - metabolism
- Mass Spectrometry -
- Metabolomics -
- Mice -
- Obesity - genetics
- Obesity - metabolism
- Receptors, Adrenergic, beta - metabolism
- Receptors, Glucocorticoid - genetics
- Signal Transduction -