OBJECTIVE: To explore the role of PP5 in fat metabolism in mice using protein phosphatase 5 (PP5) knockout mice.
Methods: 6-week-old male PP5 knockout (PP5 KO) and wild-type (WT) mice were randomly selected, and after 6 weeks of high-fat feeding, HE staining and Oil Red O staining techniques were used to investigate the liver structure and lipid droplet accumulation in the mice. The expression of lipid metabolism-related genes in liver tissue was detected by Western blotting and real-time PCR technology. Using PP5 KO and WT mouse fibroblasts simultaneously, the effect of PP5 on adipogenic differentiation was observed in vitro.
RESULTS: Compared with WT mice, PP5 KO mice after high-fat feeding showed a significant reduction in body weight compared with WT mice, and significantly fewer lipid droplets and smaller lipid droplets in the liver. Compared with WT mouse embryonic fibroblast (MEF), PP5 KO MEF cells showed significantly weaker adipogenic differentiation and smaller lipid droplets in vitro. In addition, the relative expressions of adipogenic differentiation marker genes CD36, AP2, PPARγ2 and Glut4 were significantly decreased in PP5 KO liver tissue, while the phosphorylation level of energy metabolism-related protein glucocorticoid receptor (GR) was significantly increased, and the uncoupling protein 1 (UCP1) expression was also significantly increased.
Conclusion: PP5 regulates fat metabolism in mice by regulating the dephosphorylation of GR to affect the body's fat differentiation and energy metabolism.