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

Peroxisome proliferator-activated receptors (PPARs) are nuclear hormone rec eptors that regulate the expression of many genes involved in lipid metabol ism. 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 d eveloping brain, we used reaggregated brain cell cultures prepared from dis sociated fetal rat telencephalon as experimental model. In these primary cu ltures, the fetal cells initially form random aggregates, which progressive ly acquire a tissue-specific pattern resembling that of the brain. PPARs ar e differentially expressed in these aggregates, with PPAR beta being the pr evalent isotype. PPAR alpha is present at a very low level, and PPAR gamma is absent. Cell type-specific expression analyses revealed that PPAR beta i s ubiquitous and most abundant in some neurons, whereas PPARa is predominan tly astrocytic. We chose acyl-CoA synthetases (ACSs) 1, 2, and 3 as potenti al target genes of PPAR beta and first analyzed their temporal and cell typ e-specific pattern. This analysis indicated that ACS2 and PPAR beta mRNAs h ave overlapping expression patterns, thus designating the ACS2 gene as a pu tative target of PPAR beta. Using a selective PPAR beta activator, we found that the ACS2 gene is transcriptionally regulated by PPARP beta, demonstra ting a role for PPAR beta in brain lipid metabolism.