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GSK3 is a negative regulator of the thermogenic program in brown adipocytes.
Citation | “Gsk3 Is A Negative Regulator Of The Thermogenic Program In Brown Adipocytes.”. Scientific Reports, p. 3469. . |
Center | University of Chicago |
Author | Lasse K Markussen, Sally Winther, Barton Wicksteed, Jacob B Hansen |
Abstract |
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. |
Year of Publication |
2018
|
Journal |
Scientific reports
|
Volume |
8
|
Issue |
1
|
Number of Pages |
3469
|
Date Published |
12/2018
|
ISSN Number |
2045-2322
|
DOI |
10.1038/s41598-018-21795-y
|
Alternate Journal |
Sci Rep
|
PMID |
29472592
|
PMCID |
PMC5823915
|
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