Effects of β₃-adrenoceptor on scavenger receptor class B type 1 and its signal transduction pathway in apolipoprotein E knockout mice.

It is clear that activated β₃-adrenoceptor can improve disorders of lipid metabolism, however there are few reports concerning the anti-atherosclerotic effects of β₃-adrenoceptor in the artery of apolipoprotein E knockout (Apoe(-/-)) mice. In the present study, we aimed at investigating the effects of β₃-adrenoceptor on lipids, atherosclerosis plaques, scavenger receptor class B type 1 and its signal transduction in Apoe(-/-) mice. Ten C57BL/6J mice were used as a control, and fifty age-matched Apoe(-/-) mice were randomly divided into five groups: atherosclerotic model (saline), positive control (atorvastatin), low-dose β₃-adrenoceptor agonist, high-dose β₃-adrenoceptor agonist and β₃-adrenoceptor antagonist groups. After 26 weeks on the high-fat diet, the mice received the above treatments for 12 weeks. Thoracic aortas, serum lipids, SR-B1, P-MeK1/2, P-ErK1/2 and protein kinase Cα(PKCα) activity were detected. We found that the levels of serum total cholesterol, triglyceride, very low-density lipoprotein/low-density lipoprotein cholesterol and the area of atherosclerotic plaques were significantly decreased in β3-adrenoceptor agonist-treated mice (P<0.01), while the levels of high-density lipoprotein cholesterol, thoracic aortic lumen area, activity of liver PKCα, the protein expression of SR-B1, P-MeK1/2 and P-ErK1/2 were significantly increased (P<0.01), compared with the atherosclerotic model mice. Effects of the high-dose agonist were superior to those of the low-dose (P<0.01). These findings suggest that activation of β₃-adrenoceptor reduce the plaque area in the thoracic aorta and play an important anti-atherosclerotic role by regulating lipid metabolism disorders and the SR-B1 signal transduction pathway.