Objective: To use protein phosphatase 5 (PP5) knockout mice to explore the role of PP5 in fat metabolism in mice.
Methods: 6-week-old male PP5 knockout (PP5KO) mice and wild-type (WT) mice were randomly selected. After 6 weeks of high-fat diet, the HE liver staining and the oil red color of the liver structure and lipid droplets of the mice were treated with O Dyeing. Western blot and real-time PCR technology were used to accumulate and detect the expression of lipid metabolism-related genes in liver tissue. At the same time, we used PP5KO and WT mouse fibroblasts to observe the effect of PP5 on adipogenesis in vitro.
Result: Compared with WT mice, the weight of PP5KO mice after high-fat diet was significantly reduced, liver lipid droplets were significantly reduced, and lipid droplets were smaller. In vitro experiments showed that PP5KOMEF cells have significantly weaker fat differentiation and smaller lipid droplets than WT mouse embryonic fibroblasts (MEF). In addition, in PP5KO liver tissue, the relative expression of adipocyte differentiation marker genes CD36, AP2, PPARγ2 and Glut4 were significantly reduced, and the phosphorylation level of glucocorticoid receptor (GR) increased, and proteins related to energy metabolism were increased. It is significantly increased, and the expression of uncoupling protein 1 (UCP1) is also significantly increased.
Conclusion: PP5 regulates fat metabolism in mice by regulating the dephosphorylation of GR and affecting the differentiation and energy metabolism of human fat.