Objective:To study the effects of sirolimus on hepatic lipid accumulation in mice and to expose the related mechanisms.Methods:Six-eight week C57BL/6J mice were randomly divided into three groups:mice in group A were fed with normal chaw food

mice in group B were fed with high fat diet

and mice in group C were fed with high fat diet plus sirolimus injected every other day.All mice were fed for 14 weeks. Serum biochemical parameters were analyzed by an automatic biochemical analyzer. The levels of free fatty acid（FFA）and triglyceride（TG）were measured by enzyme-linked immunosorbent assay and enzyme-coupled colorimetric assay respectively. The hepatic fatty acid translocase（FAT/CD36）protein levels were determined by Western blot. Fluorescence microscopy was used to observe the time-dependent FFA uptake by the primary hepatocytes. Results:Compared with those of group A

the body weight（q=6.68

P=0.000）

serm TG（q=4.88

P=0.045）

high-density lipoprotein（HDL）（q=6.311

P=0.002）

aspirate aminotransferase（AST）（q =6.311

P =0.001）

and liver TG（q =14.4

P =0.000）

FFA（q =18.0

P =0.000） levels of group B were highly increased. The body weight（q=7.99

P=0.000）

serum TG（q=4.636

P=0.050）

AST（q=5.16

P=0.016）

liver TG（q=8.91

P=0.000）and FFA（q=14.1

P=0.000）were significantly lower in group C than in group B. The expression of FAT/CD36 in the liver was significantly lower in group C than in group B. The time-dependent FFA uptake experiment showed that sirolimus decreased the efficiency of fluorescent FFA uptake into hepatocytes. Conclusion:Sirolimus can inhibit the uptake of FFA by hepatocytes and reduce the lipid accumulation in the liver

which may be related to CD36.