TNF-α inhibits UCP-1 expression in brown adipocytes via ERKs -: Opposite effect of p38MAPK

Tumor necrosis factor-alpha (TNF-alpha) 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-alpha on UCP-1, but not on adipogenic genes. In contrast, inhibition of p38MAPK with SB203580 potentiated the negative effect of TNF-alpha on UCP-1 and adipogenic genes. The inhibitory action of TNF-alpha was partially correlated with changes in C/EBP alpha and beta 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, (C) 2001 Published by Elsevier Science B.V. on behalf of the Federation of European Biochemical Societies.