Exploring diet-induced promoter hypomethylation and PDK4 overexpression: implications for type 2 diabetes mellitus

Background: Type 2 diabetes mellitus (T2DM) is a metabolic disorder characterized by limited metabolic flexibility in the body. Such limitation implicates the pyruvate dehydrogenase kinase 4 (PDK4) gene Poor nutrition, frequently observed among Southeast Asians usually involves excessive intakes of carbohydrates and monosodium glutamate (MSG), that have been frequently linked to an increased risk of T2DM. Methods: The 14-week study aimed to assess the effects of high-carbohydrate (HC), high-MSG (HMSG), and a combination of high-carbohydrate and high-MSG (HCHMSG) diets on the development of T2DM using male mice. To assess the effects, the male mice were divided into four groups: control (C), HC, HMSG, and HCHMSG for 14 weeks. Results: After 14 weeks, both the HC and HCHMSG groups showed signs of T2DM (168.83 ± 32.33; 156.42 ± 32.46). The blood samples from the HMSG, HC, and HCHMSG groups (57.67 ± 2.882; 49.22 ± 7.36; 48.9 ± 6.43) as well as skeletal muscle samples from the HMSG, HC, and HCHMSG groups (57.78 ± 8.54; 42.13 ± 7.25; 37.57 ± 10.42) exhibited a gradual hypomethylation. The HC groups particularly displayed significant PDK4 gene expression in skeletal muscle. A progressive overexpression of the PDK4 gene was observed as well in the HMSG, HCHMSG, and HC groups (2.03 ± 3.097; 3.21 ± 2.94; 5.86 ± 2.54). Conclusions: These findings suggest that T2DM can be induced by high-carbohydrate and high-MSG diets. However, the sole consumption of high MSG did not lead to the development of T2DM. Further research should focus on conducting long-term studies to fully comprehend the impact of a high MSG diet on individuals with pre-existing T2DM.