Objective: To use protein phosphatase 5 (PP5) gene knockout mice to explore the role of PP5 in fat metabolism in mice.
Methods: Six-week-old male PP5 knockout (PP5 KO) and wild-type (WT) mice were randomly selected. After high-fat feeding for 6 weeks, HE staining and oil red O staining techniques were applied to detect liver structure and lipid droplet accumulation in mice. For detection, use Western blotting and real-time PCR technology to detect the expression of lipid metabolism-related genes in liver tissue. At the same time, PP5 KO and WT mouse fibroblasts were used to observe the effect of PP5 on fat differentiation in vitro.
Result: Compared with WT mice, the weight of PP5 KO mice after high-fat feeding was significantly reduced compared with WT mice, and the number of lipid droplets in the liver was significantly less and the lipid droplets were smaller. In vitro experiments found that compared with WT mouse embryonic fibroblast (MEF), PP5 KO MEF cells have significantly weaker fat differentiation and smaller lipid droplets. In addition, in PP5 KO liver tissue, the relative expression of adipogenic differentiation marker genes CD36, AP2, PPARγ2 and Glut4 were significantly reduced, while the phosphorylation level of the energy metabolism related protein glucocorticoid receptor (GR) was significantly increased, and the uncoupling protein 1 (UCP1) expression also increased significantly.
Conclusion: PP5 regulates fat metabolism in mice by regulating the dephosphorylation of GR to affect body fat differentiation and energy metabolism.