Objectives To study the effect of activated β₃-AR on reverse cholesterol transport and arterial atherosclerotic plaques in apolipoprotein E knockout (ApoE^-/-) mice.

Methods Ten wide type C57BL/6J mice, 10 weeks old, were used as the normal control group. Fifty 10-week-old ApoE^-/- mice were fed a high-fat diet until 36 weeks old. They were then randomly divided into the atherosclerotic model group, atorvastatin group, β₃-adrenergic receptor (AR) agonist low-dose group, β₃-AR agonist high-dose group and the β₃-AR antagonist group, and intraperitoneally injected with either a β₃-AR agonist or antagonist twice a week for 12 weeks. Mice were sacrificed at 48 weeks old. Serum lipids were analysed using an automatic biochemical analyzer and the concentrations of cholesterol in bile and stool core sterol were analysed using gas chromatography. Thoracic aortas were taken for pathological observation.

Results Serum total cholesterol (TC), triglyceride (TG), very low density lipoprotein/low-density lipoprotein cholesterol (VLDL/LDL-C) decreased (p < 0.01); high-density lipoprotein cholesterol (HDL-C) levels in the β₃-AR agonist group increased (p < 0.01); the concentration of cholesterol in bile and stool core sterol increased (p < 0.05); the areas of thoracic aortic atherosclerotic plaques decreased (p < 0.01), compared with those of the atherosclerotic model group; and increases in the high-dose group were greater than increases in the low-dose group (p < 0.05).

Conclusions Activation of β₃-AR through elevated HDL levels in ApoE^-/- mice fed a high-fat diet promotes reverse cholesterol transport, thus reducing the thoracic aortic plaque area and promoting anti-atherosclerosis.