Peroxisome proliferator-activated receptor β regulates acyl-CoA synthetase 2 in reaggregated rat brain cell cultures

Abstract

Peroxisome proliferator-activated receptors (PPARs) are nuclear hormone receptors that regulate the expression of many genes involved in lipid metabolism. The biological roles of PPARα and PPARγ are relatively well understood, but little is known about the function of PPARβ. To address this question, and because PPARβ is expressed to a high level in the developing brain, we used reaggregated brain cell cultures prepared from dissociated fetal rat telencephalon as experimental model. In these primary cultures, the fetal cells initially form random aggregates, which progressively acquire a tissue-specific pattern resembling that of the brain. PPARs are differentially expressed in these aggregates, with PPARβ being the prevalent isotype. PPARα is present at a very low level, and PPARγ is absent. Cell type-specific expression analyses revealed that PPARβ is ubiquitous and most abundant in some neurons, whereas PPARα is predominantly astrocytic. We chose acyl-CoA synthetases (ACSs) 1, 2, and 3 as potential target genes of PPARβ and first analyzed their temporal and cell type-specific pattern. This analysis indicated that ACS2 and PPARβ mRNAs have overlapping expression patterns, thus designating the ACS2 gene as a putative target of PPARβ. Using a selective PPARβ activator, we found that the ACS2 gene is transcriptionally regulated by PPARβ, demonstrating a role for PPARβ in brain lipid metabolism.