TY - JOUR
T1 - Ras signalling regulates differentiation and UCP1 expression in models of brown adipogenesis
AU - Murholm, Maria
AU - Dixen, Karen
AU - Hansen, Jacob B
N1 - Copyright © 2010 Elsevier B.V. All rights reserved.
PY - 2010/6
Y1 - 2010/6
N2 - Background: The Ras/Raf/MEK/ERK pathway has been recognised as an important signalling module in adipogenesis and adipocyte function, but whether it promotes or inhibits the formation of fat cells has not been reconciled. Methods: Here we investigate the significance of Ras signalling intensity on two unrelated models of mouse brown adipocyte differentiation. Results: A constitutively active H-Ras mutant (Ras V12) caused a complete block of adipose conversion, as manifested by a lack of both lipid accumulation and induction of adipocyte gene expression. The Ras V12-mediated impediment of differentiation was inefficiently rescued by forced expression of the adipogenic transcription factors C/EBPα and PPARγ. However, the defective differentiation was alleviated by MEK inhibitors, suggesting that the obstruction of differentiation was dependent on activation of ERK. A dominant interfering H-Ras mutant (Ras N17) did not inhibit differentiation, but led to increased expression of genes important for energy dissipation in brown fat cells, including UCP1. General significance: These data suggest that the intensity of Ras signalling is important for differentiation and UCP1 expression in models of brown adipogenesis.
AB - Background: The Ras/Raf/MEK/ERK pathway has been recognised as an important signalling module in adipogenesis and adipocyte function, but whether it promotes or inhibits the formation of fat cells has not been reconciled. Methods: Here we investigate the significance of Ras signalling intensity on two unrelated models of mouse brown adipocyte differentiation. Results: A constitutively active H-Ras mutant (Ras V12) caused a complete block of adipose conversion, as manifested by a lack of both lipid accumulation and induction of adipocyte gene expression. The Ras V12-mediated impediment of differentiation was inefficiently rescued by forced expression of the adipogenic transcription factors C/EBPα and PPARγ. However, the defective differentiation was alleviated by MEK inhibitors, suggesting that the obstruction of differentiation was dependent on activation of ERK. A dominant interfering H-Ras mutant (Ras N17) did not inhibit differentiation, but led to increased expression of genes important for energy dissipation in brown fat cells, including UCP1. General significance: These data suggest that the intensity of Ras signalling is important for differentiation and UCP1 expression in models of brown adipogenesis.
U2 - 10.1016/j.bbagen.2010.03.008
DO - 10.1016/j.bbagen.2010.03.008
M3 - Journal article
C2 - 20307629
SN - 0304-4165
VL - 1800
SP - 619
EP - 627
JO - BBA General Subjects
JF - BBA General Subjects
IS - 6
ER -