The effects of lobeglitazone on glycaemic control and lipid metabolism in high-fat diet-induced diabetic mice

Abstract

Background and aims: The aim of this study was to compare the effects of lobeglitazone, a novel peroxisome proliferator-activated receptor-γ agonist, on glycemic control and lipid metabolism with pioglitazone in mice with type 2 diabetes.We also determined the effects of lobeglitazone and pioglitazone on glucose uptake, translocation of GLUT4 and AMPK activity in 3T3L-1 adipocytes. Materials and methods: 4-week-old C57BL/6 mice were treated with a high-fat diet for 8 weeks. After 8 weeks of high-fat diet, lobeglitazone or pioglitazone was administered once daily by oral gavage for 6 weeks. Results: Low-dose lobeglitazone (1 mg/kg) improved fasting blood glucose and insulin levels, HOMA-IR index, and blood triglyceride levels while low-dose pioglitazone did not. In 3T3L-1 cells, low-dose lobeglitazone (1 μM) significantly increased cellular glucose uptake and, GLUT4 translocation. Pioglitzone exhibited similar effects at only high dose treatment (10 μM). High-dose lobeglitazone (10 μM) increased total cellular GLUT4 protein content while pioglitazone did not. In subcutaneous fat and 3T3L-1 cells, relativemRNA expression levels for lipid synthesis were increased in both lobeglitazone and pioglitazone-treated groups compared to vehicle-treated group, but mRNA expression levels of β-oxidation-related genes and the energy expenditure-related genes were significantly increased in lobeglitazone-treated group compared to pioglitazone-treated group. In addition, lobegitazone treatment significantly increased phosphorylation of the AMP-activated protein kinase compared to pioglitazone treatment in 3T3L-1 cells. Conclusion: These results indicate that low-dose treatment of lobeglitazone might be enough to improve glucose intolerance while pioglitazone dose not. In addition, lobeglitazone could improve lipid metabolism by stimulating β-oxidation and the energy expenditure through activation of AMPK in adipocyte.