GSK3 is a negative regulator of the thermogenic program in brown adipocytes

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GSK3 is a negative regulator of the thermogenic program in brown adipocytes. / Markussen, Lasse K.; Winther, Sally; Wicksteed, Barton; Hansen, Jacob B.

In: Scientific Reports, Vol. 8, 3469, 2018, p. 1-12.

Research output: Contribution to journal › Journal article › Research › peer-review

Harvard

Markussen, LK, Winther, S, Wicksteed, B & Hansen, JB 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

APA

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, 8, 1-12. [3469]. https://doi.org/10.1038/s41598-018-21795-y

Vancouver

Markussen LK, Winther S, Wicksteed B, Hansen JB. GSK3 is a negative regulator of the thermogenic program in brown adipocytes. Scientific Reports. 2018;8:1-12. 3469. https://doi.org/10.1038/s41598-018-21795-y

Author

Markussen, Lasse K. ; Winther, Sally ; Wicksteed, Barton ; Hansen, Jacob B. / GSK3 is a negative regulator of the thermogenic program in brown adipocytes. In: Scientific Reports. 2018 ; Vol. 8. pp. 1-12.

Bibtex

@article{b2bb27857cca406f8384a15706e2bb64,
title = "GSK3 is a negative regulator of the thermogenic program in brown adipocytes",
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.",
author = "Markussen, {Lasse K.} and Sally Winther and Barton Wicksteed and Hansen, {Jacob B.}",
year = "2018",
doi = "10.1038/s41598-018-21795-y",
language = "English",
volume = "8",
pages = "1--12",
journal = "Scientific Reports",
issn = "2045-2322",
publisher = "nature publishing group",

}

RIS

TY - JOUR

T1 - GSK3 is a negative regulator of the thermogenic program in brown adipocytes

AU - Markussen, Lasse K.

AU - Winther, Sally

AU - Wicksteed, Barton

AU - Hansen, Jacob B.

PY - 2018

Y1 - 2018

N2 - 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.

AB - 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.

U2 - 10.1038/s41598-018-21795-y

DO - 10.1038/s41598-018-21795-y

M3 - Journal article

C2 - 29472592

VL - 8

SP - 1

EP - 12

JO - Scientific Reports

JF - Scientific Reports

SN - 2045-2322

M1 - 3469

ER -

ID: 198725866