Fibrate treatment induced quantitative and qualitative HDL changes associated with an increase of SR-BI cholesterol efflux capacities in rabbits
| Autor: | Arnaud Leroy, Marie-Luce Pourci, Jean-Louis Paul, Michel Leroy, Jean Dallongeville, Frank Wien, Véronique Tuloup-Minguez, Jean-Christophe Jullian, Patrice Thérond, Natalie Fournier |
|---|---|
| Rok vydání: | 2012 |
| Předmět: |
Male
medicine.medical_specialty Magnetic Resonance Spectroscopy Apolipoprotein B medicine.drug_class Fibrate Biology Biochemistry chemistry.chemical_compound Fenofibrate Internal medicine medicine Animals Scavenger receptor Receptor Hypolipidemic Agents chemistry.chemical_classification Cholesterol Circular Dichroism Fatty acid General Medicine Endocrinology chemistry biology.protein lipids (amino acids peptides and proteins) Electrophoresis Polyacrylamide Gel Rabbits Isoelectric Focusing Sphingomyelin Lipoproteins HDL medicine.drug |
| Zdroj: | Biochimie. 95(6) |
| ISSN: | 1638-6183 |
| Popis: | Fibrates are widely used as lipid lowering drugs acting as peroxisome proliferator-activated receptors α (PPARα) agonists and modulating the expression of several genes involved in lipid and lipoprotein metabolism. Much less is known on the effect of fibrates in HDL structure and composition. Therefore, we examined whether fenofibrate induces quantitative and/or qualitative modifications in HDL metabolism in the rabbit, an animal that, contrary to rodents and similar to humans, is less sensitive to peroxisome proliferators. We first demonstrated that 3-week treatment with fenofibrate (250 mg/kg/day) induced an important increase in serum apolipoprotein A-I, HDL-cholesterol and HDL-phospholipids concentrations and a relative enrichment in HDL cholesteryl ester content. Moreover, the fatty acid profiles from fenofibrate-treated rabbits displayed a dramatic increase in the serum or HDL C18:3 ω6 to C18:2 ω6 ratio suggesting higher Δ6 desaturase activity. In addition, HDL from fenofibrate-treated animals exhibited higher relative proportions of sphingomyelin, phosphatidylinositol and phosphatidylethanolamine. We then reported that fenofibrate induced major changes in the physical characteristics of HDL, mainly a higher size and a faster mobility on agarose gel electrophoresis. Finally, serum or HDL from treated rabbits exhibited higher capacity to promote cholesterol efflux from Scavenger receptor class B type I (SR-BI)-rich Fu5AH cells compared to controls. Our findings demonstrate that fenofibrate has beneficial effects in rabbits by increasing the mass of the circulating HDL pool and by modifying their composition transforming them as better acceptors of cellular cholesterol through SR-BI pathway. These effects of fenofibrate might contribute to its benefits on the prevention and treatment of atherosclerosis. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Full Text from ScienceDirect