Alteration of methylation pattern and gene expression of FTO, PPARγ and Slc2a4 on pre-diabetes-induced BALB/c mice.

Abstract

T2DM is a serious global health problem and usually caused by unhealthy diet, such diet with high carbohydrate or monosodium glutamate (MSG). In this study, we used the T2DM mice (BALB/c) model by exposing the mice with foods high in carbohydrate (HCD) or MSG (HMD) to determine the changes in molecular expression and methylation pattern of genes correlated to the development of T2DM. The data including clinical data, i.e. body weight, fasting blood glucose, and glucose tolerance, as well as gene expression, methylation pattern of glucose transport related gene (Slc2a4, FTO, and PPARγ) and also collagen deposition were measured. HCD and HMD diet for 18 weeks failed to show any clinical development of T2DM. However, it was shown that both diets significantly altered the methylation pattern and gene expression. A decrease in the expression level of Slc2a4 accompanied with a decreased methylation level in its NF-κB attachment site was observed in both groups. In addition, both treatments also showed a decrease in the expression of PPARγ in contrast to its elevated methylation level. On the other hand, a significant increase in the expression of FTO was apparent. Furthermore, an increase in collagen deposition in both groups was also detected. Overall, this study showed that an alteration on the expression and methylation pattern of the genes that are associated with glucose transportation was observed in HCD and HMD despite having no T2DM clinical development. It can potentially be a new biomarker for detection of pre-diabetes.