Ciprofibrate increases cholesteryl ester transfer protein gene expression and the indirect reverse cholesterol transport to the liver

• Published in: Lipids in health and disease 2009-11, Vol.8 (1), p.50-50, Article 50
• Main Authors: Bighetti, Eliete J B, Patrício, Patrícia R, Casquero, Andrea C, Berti, Jairo A, Oliveira, Helena C F
• Format: Article
• Language: English
• Subjects: Animals; Antilipemic agents; Apolipoprotein C-III - pharmacology; Atherosclerosis; Biological Transport; Blood cholesterol; Cholesterol - metabolism; Cholesterol Ester Transfer Proteins - genetics; Clofibric Acid - analogs & derivatives; Clofibric Acid - pharmacology; Complications and side effects; Dosage and administration; Fibric Acids; Gene Expression - drug effects; Genetic aspects; Hypertriglyceridemia - chemically induced; Liver - metabolism; Mice; Physiological aspects; PPAR alpha - agonists; Prevention; Risk factors
• ISSN: 1476-511X; 1476-511X
• DOI: 10.1186/1476-511X-8-50

CETP is a plasma protein that modulates atherosclerosis risk through its HDL-cholesterol reducing action. The aim of this work was to examine the effect of the PPARalpha agonist, ciprofibrate, on the CETP gene expression, in the presence and absence of apolipoprotein (apo) CIII induced hypertriglyceridemia, and its impact on the HDL metabolism. Mice expressing apo CIII and/or CETP and non-transgenic littermates (CIII, CIII/CETP, CETP, non-Tg) were treated with ciprofibrate during 3 weeks. Drug treatment reduced plasma triglycerides (30-43%) and non-esterified fatty acids (19-47%) levels. Cholesterol (chol) distribution in plasma lipoprotein responses to ciprofibrate treatment was dependent on the genotypes. Treated CIII expressing mice presented elevation in VLDL-chol and reduction in HDL-chol. Treated CETP expressing mice responded with reduction in LDL-chol whereas in non-Tg mice the LDL-chol increased. In addition, ciprofibrate increased plasma post heparin lipoprotein lipase activity (1.3-2.1 fold) in all groups but hepatic lipase activity decreased in treated CETP and non-Tg mice. Plasma CETP activity and liver CETP mRNA levels were significantly increased in treated CIII/CETP and CETP mice (30-100%). Kinetic studies with 3H-cholesteryl ether (CEt) labelled HDL showed a 50% reduction in the 3H-CEt found in the LDL fraction in ciprofibrate treated compared to non-treated CETP mice. This means that 3H-CEt transferred from HDL to LDL was more efficiently removed from the plasma in the fibrate treated mice. Accordingly, the amount of 3H-CEt recovered in the liver 6 hours after HDL injection was increased by 35%. Together these data showed that the PPARalpha agonist ciprofibrate stimulates CETP gene expression and changes the cholesterol flow through the reverse cholesterol transport, increasing plasma cholesterol removal through LDL.