Gemfibrozil increases the specific binding of rat-cortex nuclear extracts to a PPRE probe

Life Sci. 2003 Oct 24;73(23):2927-37. doi: 10.1016/j.lfs.2003.04.001.


PPAR agonists have been shown to elicit beneficial responses in several cell- and tissue-models of neurotoxicity. To determine if brain PPARs are responsive to the in vivo administration of PPAR agonists in a similar way to those receptors present in other anatomical localizations, such as liver, we fed rats with gemfibrozil incorporated in the diet at a dose that activates hepatic PPARalpha and produces its typical hypolipidemic effect. Rat cortex nuclear extracts presented a pattern of two specific shifted bands when incubated with a PPRE oligonucleotide. Samples from gemfibrozil-treated rats showed a significant increase in the intensity of the two shifted bands regarding control values (2.4- and 1.8-fold for the specific bands 1 and 2, respectively), indicating that orally administered gemfibrozil reaches brain tissues at concentrations sufficient to increase the specific binding of cortex nuclear extracts to an oligonucleotide mimicking a bona fide PPRE, although no changes in cortex ACO mRNA levels were produced.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acyl-CoA Oxidase
  • Administration, Oral
  • Animals
  • Cell Nucleus / drug effects
  • Cell Nucleus / metabolism
  • Cerebral Cortex / drug effects*
  • Cerebral Cortex / metabolism
  • Gemfibrozil / administration & dosage
  • Gemfibrozil / pharmacology*
  • Hypolipidemic Agents / administration & dosage
  • Hypolipidemic Agents / pharmacology*
  • Male
  • Oxidoreductases / metabolism
  • RNA, Messenger / metabolism
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, Cytoplasmic and Nuclear / genetics
  • Receptors, Cytoplasmic and Nuclear / metabolism
  • Reverse Transcriptase Polymerase Chain Reaction
  • Transcription Factors / genetics
  • Transcription Factors / metabolism


  • Hypolipidemic Agents
  • RNA, Messenger
  • Receptors, Cytoplasmic and Nuclear
  • Transcription Factors
  • Oxidoreductases
  • Acyl-CoA Oxidase
  • Gemfibrozil