Improved glucose tolerance with restored expression of glucose transporter 4 in C57BL/6 mice after a long period of high-fat diet feeding

Abstract

This study examined the effects of long-term consumption of a high-fat diet (HFD) on glucose metabolism in C57BL/6 mice. A total of 95 male 6-week-old mice were divided into normal diet (ND) and HFD groups until 16, 26, 36, 47, or 77 weeks of age. Plasma and blood glucose and insulin levels and area under the glucose curve (AUCglucose) during an intraperitoneal glucose tolerance test were measured. Quantitative real-time PCR was performed to determine the mRNA expression levels of glucose transporter 4 (GLUT4) in adipose tissue. AUCglucose levels in HFD mice at 16, 26, and 36 weeks were significantly higher than those in ND mice (p < 0.001) and significantly reduced in HFD mice at 47 and 77 weeks. Nonfasting plasma glucose concentrations in both groups were significantly decreased at 47 and 77 weeks (p ≤ 0.05). Insulin levels in HFD mice at 47 and 77 weeks were 12.5% lower than those at 36 weeks. Relative GLUT4 mRNA expression in adipose tissue of HFD mice was significantly decreased at 26 and 36 weeks and increased at 47 and 77 weeks. These data suggest that the glucose tolerance was impaired by relatively short-term high-fat feeding and significantly improved by very long periods of high-fat feeding with restored GLUT4 expression in adipose tissue in HFD mice. The differential effects of short- and long-term HFD on glucose metabolism must be considered for recharacterizing the diet-induced obesity and clarify the pathogenesis of metabolic disorders in this animal model.