Ras signalling regulates differentiation and UCP1 expression in models of brown adipogenesis

Maria Murholm; Karen Dixen; Jacob B Hansen

doi:10.1016/j.bbagen.2010.03.008

Ras signalling regulates differentiation and UCP1 expression in models of brown adipogenesis

Maria Murholm, Karen Dixen, Jacob B Hansen

Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › peer review

16 Citationer (Scopus)

Abstract

Udgivelsesdato: 2010-Jun

Originalsprog	Engelsk
Tidsskrift	BBA General Subjects
Vol/bind	1800
Udgave nummer	6
Sider (fra-til)	619-627
Antal sider	8
ISSN	0304-4165
DOI	https://doi.org/10.1016/j.bbagen.2010.03.008
Status	Udgivet - 2010

Bibliografisk note

Adgang til dokumentet

10.1016/j.bbagen.2010.03.008

Citationsformater

@article{497394d05c1e11df928f000ea68e967b,

title = "Ras signalling regulates differentiation and UCP1 expression in models of brown adipogenesis",

abstract = "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/EBPalpha and PPARgamma. 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.",

author = "Maria Murholm and Karen Dixen and Hansen, {Jacob B}",

year = "2010",

doi = "10.1016/j.bbagen.2010.03.008",

language = "English",

volume = "1800",

pages = "619--627",

journal = "BBA General Subjects",

issn = "0304-4165",

publisher = "Elsevier",

number = "6",

}

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

PY - 2010

Y1 - 2010

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/EBPalpha and PPARgamma. 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/EBPalpha and PPARgamma. 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

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