TNF‐α inhibits UCP‐1 expression in brown adipocytes via ERKs

FEBS Letters

Valladares, Amparo¹  Porras, Almudena¹  Roncero, Cesar¹  Benito, Manuel¹ 

[1] Departamento de Bioquı́mica y Biologı́a Molecular II, Instituto de Bioquı́mica (Centro Mixto del Consejo Superior de Investigaciones Cientı́ficas (C.S.I.C.) y de la Universidad Complutense de Madrid (U.C.M.)), Facultad de Farmacia, Universidad Complutense, Ciudad Universitaria, 28040 Madrid, Spain

关键词: Brown adipocyte;    Tumor necrosis factor-α;    Uncoupling protein-1;    p38 mitogen-activated protein kinase;    Extracellular-regulated kinase;    BAT;    brown adipose tissue;    C/EBP;    CAAT enhancer binding protein;    CRE;    cAMP regulatory element;    CREB;    CRE binding protein;    ERK;    extracellular-regulated kinase;    FAS;    fatty acid synthase;    p38MAPK;    p38 mitogen-activated protein kinase;    PPARγ;    peroxisome proliferator activator receptor γ;    TNF-α;    tumor necrosis factor-α;    UCP-1;    uncoupling protein-1;   

DOI  :  10.1016/S0014-5793(01)02264-5

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

Tumor necrosis factor-α (TNF-α) activates extracellular-regulated kinases (ERKs) and p38 mitogen-activated protein kinase (p38MAPK), and inhibits the expression of uncoupling protein-1 (UCP-1) and adipocyte-specific genes in rat fetal brown adipocytes. MEK inhibition with PD98059 abolished the inhibitory effect of TNF-α on UCP-1, but not on adipogenic genes. In contrast, inhibition of p38MAPK with SB203580 potentiated the negative effect of TNF-α on UCP-1 and adipogenic genes. The inhibitory action of TNF-α was partially correlated with changes in C/EBPα and β protein levels and in their DNA binding activity, suggesting a role for these transcription factors. However, other transcription factors might explain the different regulation of UCP-1 and adipogenic genes by ERKs.

【 授权许可】

Unknown