Differential expression and activation of a family of murine peroxisome proliferator-activated receptors

Proc Natl Acad Sci U S A. 1994 Jul 19;91(15):7355-9. doi: 10.1073/pnas.91.15.7355.

Abstract

To gain insight into the function of peroxisome proliferator-activated receptor (PPAR) isoforms in mammals, we have cloned and characterized two PPAR alpha-related cDNAs (designated PPAR gamma and -delta, respectively) from mouse. The three PPAR isoforms display widely divergent patterns of expression during embryogenesis and in the adult. Surprisingly, PPAR gamma and -delta are not activated by pirinixic acid (Wy 14,643), a potent peroxisome proliferator and activator of PPAR alpha. However, PPAR gamma and -delta are activated by the structurally distinct peroxisome proliferator LY-171883 and linoleic acid, respectively, indicating that each of the isoforms can act as a regulated activator of transcription. These data suggest that tissue-specific responsiveness to peroxisome proliferators, including certain fatty acids, is in part a consequence of differential expression of multiple, pharmacologically distinct PPAR isoforms.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Acetophenones / pharmacology
  • Aging / metabolism
  • Amino Acid Sequence
  • Animals
  • Base Sequence
  • Blotting, Northern
  • Cloning, Molecular
  • DNA
  • Embryo, Mammalian / metabolism
  • Linoleic Acid
  • Linoleic Acids / pharmacology
  • Mice
  • Molecular Sequence Data
  • Receptors, Cytoplasmic and Nuclear / genetics
  • Receptors, Cytoplasmic and Nuclear / metabolism*
  • Tetrazoles / pharmacology
  • Transcription Factors / genetics
  • Transcription Factors / metabolism*

Substances

  • Acetophenones
  • Linoleic Acids
  • Receptors, Cytoplasmic and Nuclear
  • Tetrazoles
  • Transcription Factors
  • LY 171883
  • DNA
  • Linoleic Acid

Associated data

  • GENBANK/U10374
  • GENBANK/U10375