Abstract
Objective To assess peripheral lymphocyte DNA methylation profiles in prediabetes using a high fat-diet-fed C57BL/6 animal model. We further evaluated whether low dose-aspirin, or low-dose aspirin in combination with metformin, could modulate global DNA methylation levels in peripheral blood lymphocytes.
Methods Twenty-eight (28) male C57BL/6 mice were used in two experimental phases. The first experiment involved animals (n=16) which were randomised to receive a low-fat diet (LFD) or high-fat diet (HFD) (n = 8/group) for 10 weeks. Whereas in the second experiment, HFD-fed mice (n=15) were randomised into 3 treatment groups, a low-dose aspirin (LDA), LDA and metformin group, and a clopidogrel group. DNA methylation profiles of were determined using flow cytometry.
Results The HFD group showed moderate weight gain and elevated postprandial blood glucose levels when compared to the LFD group after 2 weeks of HFD-feeding (p < 0.05). Interestingly, the HFD group had elevated levels of T cells expressing high levels %5-methylcytosine (p<0, 05). Notably, these elevated levels were lowered by short-term low-dose aspirin treatment.
Discussion T cells are involved in the propagation of the inflammatory response. Persistent T cell activation promotes chronic inflammation and insulin resistance. Low-dose aspirin may be effective in modulating T cell-specific global methylation.