[Deletion of CD36 gene ameliorates glucose metabolism abnormality induced by high-fat diet and promotes liver lipid accumulation].

This study aimed to investigate the effects and the underlying mechanism of CD36 gene on glucose and lipid metabolism disorder induced by high-fat diet in mice. Wild type (WT) mice and systemic CD36 knockout (CD36) mice were fed with high-fat diet for 14 weeks (n = 12). Mice were intraperitoneally injected with glucose (1 g/kg) or insulin (5 units/kg) to perform glucose tolerance test (GTT) or insulin tolerance test (ITT). Liver lipid deposition was observed by HE staining, and the contents of total triglyceride (TG), free fatty acid (FFA), aspartate aminotransferase (AST) and alanine aminotransferase (ALT) in the serum were determined by automatic biochemical analyzer. Real-time PCR and Western blot were used to detect insulin signaling pathways in liver and muscle tissues of mice. The mRNA levels of genes encoding phosphoenolpyruvate carboxykinase (PEPCK) in primary hepatocytes of mice were detected by real-time PCR, and glucose detection kit was used to detect gluconeogenesis. Co-immunoprecipitation (Co-IP) and ELISA were used to detect insulin receptor β (IRβ) tyrosine phosphorylation in mouse muscle. Real-time PCR and immunofluorescence staining (IF) were used to detect the expression and location of glucose transporter 4 (GLUT4) in muscle of mice. After high-fat diet feeding, serum FFA, TG, AST and ALT levels of CD36 mice were significantly higher than WT mice (P < 0.05). The appearance of CD36 mouse liver presented fatty degeneration, and HE staining results showed increased lipid accumulation in the liver, suggesting that CD36 knockout promoted the occurrence of fatty liver. However, CD36 mice showed decreased fasting glucose levels, increased glucose tolerance, and decreased insulin tolerance compared with WT mice (P < 0.05), suggesting that CD36 knockout protects against the abnormal glucose metabolism induced by high-fat diet. Compared with WT mice, there was no significant difference in insulin signaling pathway in CD36 mouse liver, and there were no significant differences in PEPCK expression and gluconeogenesis between the two groups of primary hepatocytes. In muscle tissue, Co-IP and ELISA experiments showed that the phosphorylation level of IRβ tyrosine was significantly increased in CD36 mice compared with that in WT mice. Besides, the levels of p-AKT in CD36 mouse muscle were significantly increased (P < 0.05). At the same time, IF experiment indicated that GLUT4 localization in cell membrane was enhanced in the muscle of CD36 mice, indicating that insulin sensitivity and glucose utilization ability were enhanced in CD36 mouse muscle. The results suggested that deletion of CD36 gene increased lipid accumulation in liver of mice with high-fat diet, but had no significant effect on liver gluconeogenesis. CD36 deficiency improves the abnormal glucose metabolism in mice with high-fat diet mainly through improving insulin sensitivity of muscle tissue and promoting GLUT4-mediated glucose utilization.