GSK3 is a negative regulator of the thermogenic program in brown adipocytes
| Autor: | Lasse K. Markussen, Sally Winther, Barton Wicksteed, Jacob B. Hansen |
|---|---|
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
MAPK/ERK pathway FGF21 MAP Kinase Signaling System Science Primary Cell Culture macromolecular substances Article Glycogen Synthase Kinase 3 Mice 03 medical and health sciences Oxygen Consumption GSK-3 Receptors Adrenergic beta Brown adipose tissue medicine Animals Glucose homeostasis Protein Kinase Inhibitors Uncoupling Protein 1 Multidisciplinary Kinase Chemistry Thermogenesis Cyclic AMP-Dependent Protein Kinases Thermogenin 3. Good health Cell biology Fibroblast Growth Factors Adipocytes Brown Glucose 030104 developmental biology medicine.anatomical_structure Gene Expression Regulation Medicine Phosphorylation Insulin Resistance Energy Metabolism Signal Transduction |
| Zdroj: | Markussen, L K, Winther, S, Wicksteed, B & Hansen, J B 2018, ' GSK3 is a negative regulator of the thermogenic program in brown adipocytes ', Scientific Reports, vol. 8, 3469, pp. 1-12 . https://doi.org/10.1038/s41598-018-21795-y Scientific Reports Scientific Reports, Vol 8, Iss 1, Pp 1-12 (2018) |
| ISSN: | 2045-2322 |
| Popis: | Brown adipose tissue is a promising therapeutic target in metabolic disorders due to its ability to dissipate energy and improve systemic insulin sensitivity and glucose homeostasis. β-Adrenergic stimulation of brown adipocytes leads to an increase in oxygen consumption and induction of a thermogenic gene program that includes uncoupling protein 1 (Ucp1) and fibroblast growth factor 21 (Fgf21). In kinase inhibitor screens, we have identified glycogen synthase kinase 3 (GSK3) as a negative regulator of basal and β-adrenergically stimulated Fgf21 expression in cultured brown adipocytes. In addition, inhibition of GSK3 also caused increased Ucp1 expression and oxygen consumption. β-Adrenergic stimulation triggered an inhibitory phosphorylation of GSK3 in a protein kinase A (PKA)-dependent manner. Mechanistically, inhibition of GSK3 activated the mitogen activated protein kinase (MAPK) kinase 3/6-p38 MAPK-activating transcription factor 2 signaling module. In summary, our data describe GSK3 as a novel negative regulator of β-adrenergic signaling in brown adipocytes. |
| Databáze: | OpenAIRE |
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