Differential role of PPARγ in the regulation of UCP‐1 and adipogenesis by TNF‐α in brown adipocytes

FEBS Letters

Valladares, Amparo²  Porras, Almudena²  Álvarez, Alberto M.¹  Roncero, Cesar²  Benito, Manuel² 

[1] Centro de Citometrı́a de Flujo y Microscopı́a Confocal, Facultad de Farmacia, Universidad Complutense, Ciudad Universitaria, 28040 Madrid, Spain;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.)), Ciudad Universitaria, 28040 Madrid, Spain

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

DOI  :  10.1016/S0014-5793(02)02762-X

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

Extracellular regulated kinases (ERKs) mediate the inhibitory effect of tumor necrosis factor α (TNF-α) on uncoupling protein-1 (UCP-1), but not on lipid accumulation. TNF-α-induced ERK-dependent peroxisome proliferator activator receptor γ (PPARγ) phosphorylation could be responsible for UCP-1 downregulation. Thus, the negative effect of TNF-α on UCP-1 mRNA expression at 4–5 h, under basal conditions or in cells treated with the PPARγ agonist, rosiglitazone, was reversed by the MEK1 inhibitor PD98059. In contrast, fatty acid synthase and malic enzyme mRNA downregulation was not prevented. Moreover, rosiglitazone has no positive effect on adipogenic gene expression or lipid accumulation. Therefore, there is a differential regulation of thermogenic and adipogenic differentiation by PPARγ, which might account for the differences in the TNF-α regulation through ERKs.

【 授权许可】

Unknown