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

PPARalpha is a lipid-activable transcription factor that mediates the adaptive response to fasting. Recent data indicate an important role of brain PPARalpha in physiological functions. However, it has not yet been shown whether PPARalpha in brain can be activated in the fasting state. Here we demonstrate that fasting of rats increased mRNA concentrations of typical PPARalpha target genes implicated in beta-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 PPARalpha in brain and pituitary gland. Furthermore, pituitary prolactin and luteinizing hormone-beta mRNA concentrations were increased upon fasting in wild-type mice but not in mice lacking PPARalpha. For proopiomelanocortin and thyrotropin-beta, genotype-specific differences in pituitary mRNA concentrations were observed. Thus, PPARalpha seems to be involved in transcriptional regulation of pituitary hormones.