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Differential role of PPARγ in the regulation of UCP‐1 and adipogenesis by TNF‐α in brown adipocytes
Author(s) -
Porras Almudena,
Valladares Amparo,
Álvarez Alberto M.,
Roncero Cesar,
Benito Manuel
Publication year - 2002
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/s0014-5793(02)02762-x
Subject(s) - adipogenesis , rosiglitazone , endocrinology , downregulation and upregulation , medicine , chemistry , peroxisome proliferator activated receptor , mapk/erk pathway , tumor necrosis factor alpha , kinase , receptor , biology , biochemistry , adipose tissue , gene
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.