Mode of action of peroxisome proliferators as hypolipidemic drugs. Suppression of apolipoprotein C-III - PubMed (original) (raw)
. 1995 Jun 2;270(22):13470-5.
doi: 10.1074/jbc.270.22.13470.
Affiliations
- PMID: 7768950
- DOI: 10.1074/jbc.270.22.13470
Free article
Mode of action of peroxisome proliferators as hypolipidemic drugs. Suppression of apolipoprotein C-III
R Hertz et al. J Biol Chem. 1995.
Free article
Abstract
The hypolipidemic effect exerted by beta,beta'-tetramethyl-hexadecanedioic acid (Medica 16) is accounted for by enhanced catabolism of plasma triglyceride-rich lipoproteins due to a decrease in plasma apolipoprotein C-III (Frenkel, B., Mayorek, N., Hertz, R., and Bar-Tana, J. (1988) J. Biol. Chem. 263, 8491-8497; Frenkel, B., Bishara-Shieban, J., and Bar-Tana, J. (1994) Biochem. J. 298, 409-414). Decrease in apolipoprotein C-III exerted by peroxisome proliferators/hypolipidemic amphipathic carboxylates (e.g. Medica 16, fibrate drugs) is shown here to result from suppression of apolipoprotein C-III gene expression. Transcriptional suppression of apolipoprotein C-III is due to transcriptional suppression of hepatic nuclear factor (HNF)-4 as well as displacement of HNF-4 from the apolipoprotein C-III promoter. HNF-4 displacement exerted by peroxisome proliferators/hypolipidemic amphipathic carboxylates is mediated by the peroxisome proliferators activated receptor (PPAR). Transcriptional suppression of HNF-4-enhanced genes (e.g. apolipoprotein C-III) along with transcriptional activation of peroxisomal and other genes by hypolipidemic drugs may account for their broad spectrum pharmacological effect.
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