Expression of PPAR, RXR isoforms and fatty acid transporting proteins in the rat and human gastrointestinal tracts

J Pharm Sci. 2005 Feb;94(2):363-72. doi: 10.1002/jps.20264.

Abstract

Dietary fatty acid (FA) absorption across the gastrointestinal (GI) tract is of critical importance for sustenance, however, excessive FA absorption has also been linked to metabolic syndrome and associated disorders. The expression of isoforms that regulate the dietary FA absorption are not as well characterized in the GI tract as they are elsewhere. Peroxisome proliferator-activated receptors (PPARalpha, beta, and gamma) and 9-cis-retinoic acid receptors (RXRalpha, beta, and gamma) are nuclear hormone transcription factors that control FA homeostasis, in part through the regulation of expression of membrane-bound FA transporting proteins. The present study was designed to elucidate the expression of PPAR and RXR isoforms and FA transporting proteins (FABPpm and FAT/CD36) in the rat and human GI tracts using reverse transcriptase-polymerase chain reaction (RT-PCR), immunoblotting, and immunohistochemical staining. The results revealed rat GI expression of all the PPAR and RXR isoforms, FABPpm and FAT/CD36. PPARalpha, PPARbeta, PPARgamma, RXRalpha, FABPpm, and FAT/CD36 isoforms exhibited ubiquitous expression in human GI tract, whereas RXRbeta was not detected. RXRgamma was observed in a majority of the human GI samples. These results provide a physiological foundation for rational drug design and drug delivery for the mitigation of metabolic syndrome and associated disorders to normalize intestinal FA absorption.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Fatty Acid Transport Proteins
  • Female
  • Gastrointestinal Tract / metabolism*
  • Humans
  • Immunoblotting
  • Immunohistochemistry
  • Membrane Transport Proteins / genetics
  • Membrane Transport Proteins / metabolism*
  • Peroxisome Proliferator-Activated Receptors / genetics
  • Peroxisome Proliferator-Activated Receptors / metabolism*
  • Protein Isoforms / genetics
  • Protein Isoforms / metabolism
  • RNA, Messenger / metabolism
  • Rats
  • Rats, Sprague-Dawley
  • Retinoid X Receptors / genetics
  • Retinoid X Receptors / metabolism*
  • Reverse Transcriptase Polymerase Chain Reaction

Substances

  • Fatty Acid Transport Proteins
  • Membrane Transport Proteins
  • Peroxisome Proliferator-Activated Receptors
  • Protein Isoforms
  • RNA, Messenger
  • Retinoid X Receptors