Fasting Upregulates PPAR Target Genes in Brain and Influences Pituitary Hormone Expression in a PPAR Dependent Manner

PPAR α is a lipid-activable transcription factor that mediates the adaptive response to fasting. Recent data indicate an important role of brain PPAR α in physiological functions. However, it has not yet been shown whether PPAR α in brain can be activated in the fasting state. Here we demonstrate that fasting of rats increased mRNA concentrations of typical PPAR α target genes implicated in β -oxidation of fatty acids (acyl-CoA oxidase, carnitine palmitoyltransferase-1, medium chain acyl-CoA dehydrogenase) and ketogenesis (mitochondrial 3-hydroxy-3-methylglutaryl-CoA synthase) in pituitary gland and partially also in frontal cortex and diencephalon compared to nonfasted animals. These data strongly indicate that fasting activates PPAR α in brain and pituitary gland. Furthermore, pituitary prolactin and luteinizing hormone- β mRNA concentrations were increased upon fasting in wild-type mice but not in mice lacking PPAR α . For proopiomelanocortin and thyrotropin- β , genotype-specific differences in pituitary mRNA concentrations were observed. Thus, PPAR α seems to be involved in transcriptional regulation of pituitary hormones.