[Animal modeling] - Effect of long-term high protein diet on liver steatosis and fat accumulation in OVX mice

  Objective To investigate the effects of long-term high protein diet on liver and adipose tissue of ovariectomized mice and the role of glucagon like peptide-1.

  Methods Thirty two 8-week old C57BL/6 female mice were randomly divided into control group, model group, high protein (OVX+HP) group and low protein (OVX+LP) group with 8 mice in each group. After ovariectomy, model group, high protein group and low protein group were given standard diet, high protein diet and low protein diet respectively; The control group received the same operation to preserve the ovaries and was given standard diet. The weight of mice was weighed every week. After being killed at the end of 24 weeks, the liver, colon and retroperitoneal adipose tissue were taken and weighed; HE staining was used to observe the pathological changes of liver and retroperitoneal fat; The content of GLP-1 in serum was detected by ELISA; Real time quantitative PCR was used to detect the expression of hepatic sterol regulatory element binding protein-1c (SREBP-1c) and GLP-1 mRNA in colon tissues. Immunohistochemical staining was used to detect the expression of hepatic SREBP-1c protein.

  Results At the end of 24 weeks, compared with the control group, the model group gained weight (P<0.05) and increased retroperitoneal adipose tissue (P<0.05); In HE staining model group, a large number of lipid droplets were found in liver cells, and the volume of retroperitoneal adipose tissue cells increased; The expression of GLP-1 mRNA in colon tissue decreased (P<0.05), the content of GLP-1 in plasma decreased (P<0.05), the expression of SREBP-1c mRNA in liver tissue increased (P<0.05), and the expression of SREBP-1c protein increased; Compared with the model group, the weight of the high protein group decreased (P<0.01), and the retroperitoneal fat decreased significantly (P<0.001). A small amount of fat droplets were found in the liver cells of the pathological section, and the volume of retroperitoneal fat cells decreased; The expression of GLP-1 mRNA in colon tissue increased (P<0.01), the content of GLP-1 in plasma increased (P<0.001), the expression of SREBP-1c mRNA in liver decreased (P<0.001), and the expression of SREBP-1c protein decreased; There was no significant difference in body weight, retroperitoneal fat, GLP-1, SREBP-1c mRNA expression between the low protein group and the model group.

  Conclusion Long term high protein diet can improve the weight gain and liver steatosis of OVX mice, which may be related to the fact that high protein diet can promote the intestinal secretion of GLP-1, down regulate the mRNA and protein expression of liver SREBP-1c, and play an estrogen like role.