| Autor: |
Beyer, Thomas, Chen, Yanqun, Porter, Regina, Lu, Deshun, Schmidt, Robert, Mantlo, Nathan, Konrad, Robert, Cao, Guoqing |
| Zdroj: |
Lipids; Jul2008, Vol. 43 Issue 7, p611-618, 8p |
| Abstrakt: |
Peroxisome proliferator-activated receptor α (PPARα) belongs to the nuclear receptor superfamily that regulates multiple target genes involved in lipid metabolism. Cholesterol ester transfer protein (CETP) is a secreted glycoprotein that modifies high-density lipoprotein (HDL) particles. In humans, plasma CETP activity is inversely correlated with HDL cholesterol levels. We report here that PPARα agonists increase CETP mRNA, protein and accordingly its activity. In a human CETP transgenic animal model harboring the natural flanking regions (Jiang et al. in J Clin Investigat 90:1290–1295, 1992), both fenofibrate and a specific synthetic PPARα agonist LY970 elevated human CETP mRNA in liver, serum protein and CETP activity. In hamsters, the endogenous liver CETP mRNA level and the serum CETP activity were dose-dependently upregulated by fenofibrate. In addition Wy14643, a PPARα agonist, also significantly elevated CETP mRNA and activity. In a carcinoma cell line of hepatic origin, HepG2 cells, overexpression of PPARα resulted in increased CETP mRNA and agonist treatment further elevated CETP mRNA levels. We conclude that PPARα agonists upregulate CETP expression and activity and may play an important role in PPARα (agonist mediated HDL cholesterol homeostasis in humans. [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
| Externí odkaz: |
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