Effect of atorvastatin on SR-BI expression and HDL-induced cholesterol efflux in adipocytes of hypercholesterolemic rabbits.

Background: Adipose tissue contains a large amount of cholesterol and performs a buffer function for circulating cholesterol. Scavenger receptor class B type I (SR-BI) might play a significant role in adipocytes cholesterol metabolism through mediation of cholesterol efflux. We evaluated the effect of atorvastatin on SR-BI expression and HDL-induced cholesterol efflux in adipocytes from hypercholesterolemic rabbits.

Methods: Sixteen rabbits fed with high-cholesterol diet for 8 weeks were randomly divided into 2 groups: (1) maintained on a high cholesterol diet for 6 weeks (n=8); (2) the same cholesterol diet plus atorvastatin (2.5 mg/kg/day) for 6 weeks (n=8). Control group (n=5) was fed with normal diet for 14 weeks. Subcutaneous adipose was collected for adipocyte culture. Reverse transcription polymerase chain reaction (RT-PCR) was used to evaluate adipocytes SR-BI mRNA expression. Cholesterol efflux rate was determined through measuring release of radioactivity from (3)H-cholesterol prelabeled cells into medium containing high-density lipoprotein (HDL). The direct effect of atorvastatin on SR-BI mRNA expression in primary rabbit adipocytes was assayed.

Results: High-cholesterol diet decreased SR-BI mRNA expression and reduced HDL-induced cholesterol efflux rate in adipocytes. Six weeks of atorvastatin treatment significantly enhanced the cholesterol efflux from adipocytes, which was related to the increased mRNA expression of SR-BI (r=0.58, P<0.05). Adipocytes SR-BI mRNA expression were negatively correlated with the serum total cholesterol levels at the end of the study (r=-0.46, P<0.05). Atorvastatin dose-dependently stimulated SR-BI mRNA expression in cultured adipocytes.

Conclusion: Atorvastatin can up-regulate SR-BI mRNA expression and promote the HDL-induced cholesterol efflux in adipocytes from hypercholesterolemic rabbits possibly through lowering serum cholesterol levels and directly stimulating SR-BI mRNA expression.