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  • Title: Differential role of PPAR gamma in the regulation of UCP-1 and adipogenesis by TNF-alpha in brown adipocytes.
    Author: Porras A, Valladares A, Alvarez AM, Roncero C, Benito M.
    Journal: FEBS Lett; 2002 Jun 05; 520(1-3):58-62. PubMed ID: 12044870.
    Abstract:
    Extracellular regulated kinases (ERKs) mediate the inhibitory effect of tumor necrosis factor alpha (TNF-alpha) on uncoupling protein-1 (UCP-1), but not on lipid accumulation. TNF-alpha-induced ERK-dependent peroxisome proliferator activator receptor gamma (PPAR gamma) phosphorylation could be responsible for UCP-1 downregulation. Thus, the negative effect of TNF-alpha on UCP-1 mRNA expression at 4-5 h, under basal conditions or in cells treated with the PPAR gamma 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 PPAR gamma, which might account for the differences in the TNF-alpha regulation through ERKs.
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