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

Peroxisome proliferator-activated receptors (PPARs) are nuclear hormone receptors that regulate the expression of many genes involved in lipid metabolism. The biological roles of PPAR alpha and PPAR gamma are relatively well understood, but little is known about the function of PPAR beta. To address this question, and because PPAR beta 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 PPAR beta being the prevalent isotype. PPAR alpha is present at a very low level, and PPAR gamma is absent. Cell type-specific expression analyses revealed that PPAR beta is ubiquitous and most abundant in some neurons, whereas PPARa is predominantly astrocytic. We chose acyl-CoA synthetases (ACSs) 1, 2, and 3 as potential target genes of PPAR beta and first analyzed their temporal and cell type-specific pattern. This analysis indicated that ACS2 and PPAR beta mRNAs have overlapping expression patterns, thus designating the ACS2 gene as a putative target of PPAR beta. Using a selective PPAR beta activator, we found that the ACS2 gene is transcriptionally regulated by PPARP beta, demonstrating a role for PPAR beta in brain lipid metabolism.