Differential role of PPAR gamma in the regulation of UCP-1 and adipogenesis by TNF-alpha in brown adipocytes.

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.

journal_name

FEBS Lett

journal_title

FEBS letters

authors

Porras A,Valladares A,Alvarez AM,Roncero C,Benito M

doi

10.1016/s0014-5793(02)02762-x

keywords:

subject

Has Abstract

pub_date

2002-06-05 00:00:00

pages

58-62

issue

1-3

eissn

0014-5793

issn

1873-3468

pii

S001457930202762X

journal_volume

520

pub_type

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