Fatty acids and the insulin-sensitizing agent Pioglitazone (Piog) accelerate expression of adipose specific genes (e.g. adipose fatty acid binding protein (a-FABP)) and fat-cell terminal differentiation. We hypothesized that the induction of terminal differentiation of adipocytes by insulin, requires an increase in expression and/or nuclear localization of the adipogenic factor peroxisome proliferator activated receptor γ2 (PPARγ2) and that this increase in PPARγ2 is enhanced by Piog. Northern and western blot analysis revealed that stimulation a-FABP expression by insulin and Piog in 3T3-L1 cells was not accompanied by an increase in PPARγ2 mRNA or protein levels. However, PPARγ2 's binding partner RXRα, which was not detected in preadipocytes. became detectable in the nucleus after 48 hours and increased 10 fold after 5 days. This increase in RXRα preceded a-FABP expression but were not further increased by Piog. On the other hand DNA interactions between the heterodimer PPARγ2/RXRa (ARF6) and the adipose specific elements ARE6 and ARE7 were increased during differentiation and amplified by Piog. Our results suggest that Piog and insulin interact to stimulate the activation of ARF6 binding through post-translational mechanisms.
|Original language||English (US)|
|State||Published - Dec 1 1997|
ASJC Scopus subject areas
- Molecular Biology