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

S. A. Kliewer; B. M. Forman; B. Blumberg; E. S. Ong; U. Borgmeyer; D. J. Mangelsdorf; K. Umesono; R. M. Evans

doi:10.1073/pnas.91.15.7355

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

S. A. Kliewer, B. M. Forman, B. Blumberg, E. S. Ong, U. Borgmeyer, D. J. Mangelsdorf, K. Umesono, R. M. Evans

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Abstract

To gain insight into the function of peroxisome proliferator-activated receptor (PPAR) isoforms in mammals, we have cloned and characterized two PPARα-related cDNAs (designated PPARγ and -δ, respectively) from mouse. The three PPAR isoforms display widely divergent patterns of expression during embryogenesis and in the adult. Surprisingly, PPARγ and -δ are not activated by pirinixic acid (Wy 14,643), a potent peroxisome proliferator and activator of PPARα. However, PPARγ and -δ 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.

Original language	English (US)
Pages (from-to)	7355-7359
Number of pages	5
Journal	Proceedings of the National Academy of Sciences of the United States of America
Volume	91
Issue number	15
DOIs	https://doi.org/10.1073/pnas.91.15.7355
State	Published - Jul 19 1994

Keywords

fatty acid
nuclear hormone receptors
β-oxidation

ASJC Scopus subject areas

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Kliewer, S. A., Forman, B. M., Blumberg, B., Ong, E. S., Borgmeyer, U., Mangelsdorf, D. J., Umesono, K., & Evans, R. M. (1994). Differential expression and activation of a family of murine peroxisome proliferator-activated receptors. Proceedings of the National Academy of Sciences of the United States of America, 91(15), 7355-7359. https://doi.org/10.1073/pnas.91.15.7355

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AU - Borgmeyer, U.

AU - Mangelsdorf, D. J.

AU - Umesono, K.

AU - Evans, R. M.

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N2 - To gain insight into the function of peroxisome proliferator-activated receptor (PPAR) isoforms in mammals, we have cloned and characterized two PPARα-related cDNAs (designated PPARγ and -δ, respectively) from mouse. The three PPAR isoforms display widely divergent patterns of expression during embryogenesis and in the adult. Surprisingly, PPARγ and -δ are not activated by pirinixic acid (Wy 14,643), a potent peroxisome proliferator and activator of PPARα. However, PPARγ and -δ 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.

AB - To gain insight into the function of peroxisome proliferator-activated receptor (PPAR) isoforms in mammals, we have cloned and characterized two PPARα-related cDNAs (designated PPARγ and -δ, respectively) from mouse. The three PPAR isoforms display widely divergent patterns of expression during embryogenesis and in the adult. Surprisingly, PPARγ and -δ are not activated by pirinixic acid (Wy 14,643), a potent peroxisome proliferator and activator of PPARα. However, PPARγ and -δ 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.

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

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