| Popis: |
We have previously shown that a mixture of dietary conjugated derivatives of linoleic acid (conjugated linoleic acid, CLA) induces peroxisome proliferator-responsive enzymes and modulates hepatic lipid metabolism in vivo. The present studies demonstrate that CLA is a high affinity ligand and activator of peroxisome proliferator-activated receptor α (PPARα) and induces accumulation of PPAR-responsive mRNAs in a rat hepatoma cell line. Using a scintillation proximity assay (SPA), CLA isomers were shown to be ligands for human PPARα with a rank order of potency of (9Z,11E)>(10E,12Z)>(9E,11E)> furan-CLA (IC50 values from 140 nm to 400 nm). Levels of acyl-CoA oxidase (ACO), liver fatty acid-binding protein (L-FABP), and cytochrome P450IVA1 (CYP4A1) mRNA were induced by CLA in FaO hepatoma cells. Even though linoleate and CLA were incorporated into lipids of hepatoma cells to the same extent, linoleate had little or no effect on ACO, CYP4A1, or L-FABP mRNA. In agreement with its binding potency, (9Z,11E)-CLA was the most efficacious PPARα activator in the mouse PPARα-GAL4(UAS)5-CAT reporter system. These data indicate that CLA is a ligand and activator of PPARα and its effects on lipid metabolism may be attributed to transcriptional events associated with this nuclear receptor. Also, (9Z,11E)-CLA is one of the most avid fatty acids yet described as a PPARα ligand.—Moya-Camarena, S. Y., J. P. Vanden Heuvel, S. G. Blanchard, L. A. Leesnitzer, and M. A. Belury. Conjugated linoleic acid is a potent naturally occurring ligand and activator of PPARα. J. Lipid Res. 1999. 40: 1426–1433. |
