Effect of the PPARγ modulation on the reverse pathway of cholesterol

Abstract

Introduction: Nuclear receptor LXRα (liver X receptor alpha) has a beneficial effect on the reverse pathway of cholesterol and reverts some defects in the lipid metabolism that are related with cardiovascular risk. LXRα activity is modulated by agonists of the nuclear receptor PPARγ (Peroxisome Proliferator-Activated Receptor gamma), that are used for type 2 Diabetes treatment. Objective: To observe LXRα gene expression and some genes that it regulates, after the treatment with a PPARγ agonist in the absence of estrogens. Method: 18 New Zealand female rabbits were ophorectomized. Three groups selected themselves randomly. In two groups, were treated with hypercholesterolemic diet during 3 weeks alternating with normal diet for a total of 24 weeks, to one of these groups, administered placebo (group 1, n=6) and to another one rosiglitazone 3 mg/Kg/día (group 2, n=6). The third group took like group control with normal diet. The expression of the genes of lxrα, abca1 and il-1β was determined by means of RT-PCR. Results: An increase in LXRά mRNA expression was observed in liver, without any variationin ABCA1 in artery. A reduction on IL-1β levels in artery after rosiglitazone therapy was observed. Conclusion: PPARγ activation increases LXRα function in the absence of estrogens. However PPARγ might execute some beneficial effect on reverse cholesterol pathway in a different route from LXRα/ABCA1 pathway.

Keywords

• Reverse pathway of cholesterol
• LXRα
• ABCA1
• IL1β
• PPARγ
• rosiglitazone