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Peroxisome Proliferator‐Activated Receptors and Lipid Metabolism a
Author(s) -
KELLER HANSJÖRG,
MAHFOUDI ABDERRAHIM,
DREYER CHRISTINE,
HIHI ABDELMADJID K.,
MEDIN JEFFREY,
OZATO KEIKO,
WAHLI WALTER
Publication year - 1993
Publication title -
annals of the new york academy of sciences
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.712
H-Index - 248
eISSN - 1749-6632
pISSN - 0077-8923
DOI - 10.1111/j.1749-6632.1993.tb32279.x
Subject(s) - lipid metabolism , peroxisome proliferator , peroxisome , peroxisome proliferator activated receptor , receptor , chemistry , metabolism , peroxisome proliferator activated receptor alpha , biochemistry , nuclear receptor , endocrinology , medicine , biology , transcription factor , gene
PPARs are nuclear hormone receptors which, like the retinoid, thyroid hormone, vitamin D, and steroid hormone receptors, are ligand-activated transcription factors mediating the hormonal control of gene expression. Two lines of evidence indicate that PPARs have an important function in fatty acid metabolism. First, PPARs are activated by hypolipidemic drugs and physiological concentrations of fatty acids, and second, PPARs control the peroxisomal beta-oxidation pathway of fatty acids through transcriptional induction of the gene encoding the acyl-CoA oxidase (ACO), which is the rate-limiting enzyme of the pathway. Furthermore, the PPAR signaling pathway appears to converge with the 9-cis retinoic acid receptor (RXR) signaling pathway in the regulation of the ACO gene because heterodimerization between PPAR and RXR is essential for in vitro binding to the PPRE and because the strongest stimulation of this gene is observed when both receptors are exposed simultaneously to their activators. Thus, it appears that PPARs are involved in the 9-cis retinoic acid signaling pathway and that they play a pivotal role in the hormonal control of lipid metabolism.