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Identification of fatty acid methyl ester as naturally occurring transcriptional regulators of the members of the peroxisome proliferator‐activated receptor family
Author(s) -
Schmidt Azriel,
Vogel Robert L.,
Witherup Keith M.,
Rutledge Su Jane,
Pitzenberger Steven M.,
Adam Mohammed,
Rodan Gideon A.
Publication year - 1996
Publication title -
lipids
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.601
H-Index - 120
eISSN - 1558-9307
pISSN - 0024-4201
DOI - 10.1007/bf02524285
Subject(s) - lipidology , peroxisome , peroxisome proliferator activated receptor alpha , peroxisome proliferator activated receptor , clinical chemistry , identification (biology) , peroxisome proliferator activated receptor gamma , receptor , chemistry , fatty acid , biochemistry , peroxisome proliferator , microbiology and biotechnology , nuclear receptor , biology , transcription factor , gene , botany
The nuclear hormone receptors NUC‐1 (PPARδ) and PPARα are members of the peroxisome proliferator‐activated receptor (PPAR) family. The members of this receptor family are activated by agents that stimulate peroxisome proliferation, free fatty acids, prostaglandin J2 metabolites, and agents considered for the therapy of insulin‐independent diabetes mellitus. To identify putative physiological agents that activate NUC‐1, we tested the ability of acetone extracts of various rat tissues to activate the transcription of an MMTV‐luciferase reporter gene, via a GR/NUC‐1 hybrid receptor. GR/NUC‐1 contains the ligand binding region of the NUC‐1 receptor and the DNA binding domain of the glucocorticoid receptor. Using this assay, we found stimulatory activity in the pancreas, which upon purification and characterization was identified as methylpalmitate, known to be enriched in pancreatic lipids. In addition, we determined that ethyl esters of palmitic and oleic acids are also potent activators of this receptor. thus, fatty acid ester formation may control the cellular concentrations of fatty acids, and acyl‐ester formation may play a role in the control of metabolic pathways and the activation of the PPAR.