【Animal Modeling】-Effect of long-term high-protein diet on hepatic steatosis and fat accumulation in OVX mice

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

  Methods Thirty-two 8-week-old C57BL/6 female mice were randomly divided into control (Control) group, model (OVX) group, high-protein (OVX+HP) group, and low-protein (OVX+LP) group, with 8 mice in each group. Mice in the model group, high-protein group, and low-protein group were given standard diet, high-protein diet, and low-protein diet after ovariectomy, respectively; the control group underwent the same operation to preserve ovaries and were given standard diet. The weight of the mice was weighed every week, and after being sacrificed at the end of the 24th week, the liver, colon and retroperitoneal adipose tissue were collected, and the adipose tissue was weighed; HE staining was used to observe the pathological changes of the liver and retroperitoneal fat; enzyme-linked immunosorbent assay (ELISA) Serum GLP-1 content was detected by real-time quantitative PCR; sterol regulatory element binding protein-1c (SREBP-1c) and GLP-1 mRNA expression in colon tissue were detected by real-time quantitative PCR. The expression of hepatic SREBP-1c protein was detected by staining method.

  Results At the end of 24, compared with the control group, the model group had increased body weight ( P< 0. 05) and increased retroperitoneal adipose tissue ( P < 0. 05); a large number of lipid droplets and retroperitoneal fat were found in the hepatocytes of the HE staining model group. The volume of 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), and the mRNA expression of SREBP-1c in liver tissue increased (P<0.05). P<0.05), the expression of SREBP-1c protein increased; compared with the model group, the high protein group had a lower body weight (P<0.01), a significant reduction in retroperitoneal fat (P<0.001), and hepatocytes in pathological sections. A small number of lipid droplets were seen in the internal organs, and the volume of retroperitoneal adipocytes was reduced; the expression of GLP-1 mRNA in colon tissue increased (P<0.01), the content of GLP-1 in plasma increased (P<0.001), and the expression of SREBP-1c in liver increased. The mRNA expression decreased (P<0.001), and the protein expression of SREBP-1c decreased; there was no significant difference between the low protein group and the model group in terms of body weight, retroperitoneal fat, and mRNA expression of GLP-1 and SREBP-1c.

  Conclusion Long-term high-protein diet can improve body weight gain and hepatic steatosis in OVX mice, which may be related to the high-protein diet promotes intestinal secretion of GLP-1, down-regulates the mRNA and protein expression of hepatic SREBP-1c, and exerts an estrogen-like effect.