Effects of exercise intensity and diet on cardiac tissue structure and FGF21/β-Klotho signaling in type 2 diabetic mice: a comparative study of HFD and HFD + STZ induced type 2 diabetes models in mice.

Background: Structural heart disease is one of the leading causes of death in people with type 2 diabetes (T2D), which is not known to have an effect on exercise training. The aim of this study was to compare the effects of high-intensity interval training (HIIT) and moderate-intensity continuous training (MICT) on heart tissue structure, the serum level of FGF21 and the heart tissue level of β-Klotho, an FGF21 coreceptor, in HFD and HFD + STZ-induced diabetic mice.

Methods: Thirty-six male C57BL/6J mice were divided into high-fat diet (HFD) and normal chow diet (ND) groups. After 20 weeks of diet, the HFD mice were divided into HFD and HFD + STZ groups, and the latter group was injected with STZ. Then, the mice in the ND, HFD and HFD + STZ groups were divided into three subgroups of control (C), HIIT and MICT, and mice were placed in one of nine groups ND-C, ND-HIIT, ND-MICT, HFD-C, HFD-HIIT, HFD-MICT, HFD + STZ-C, HFD + STZ-HIIT, and HFD + STZ-MICT. The mice in the exercise training (ET) groups were run on a treadmill for eight weeks. Finally, the tissue and serum samples were collected and analyzed by two-way ANOVA.

Results: Statistical analyses showed that the main effect of diabetes inducing model (DIM) was significant for all variables (p < 0.05), except vascular density (p = 0.055); the main effect of ET type on fasting blood glucose and FGF21 was significant (p < 0.001); and the interaction was significant for fasting blood glucose, heart weight and FGF21 (p < 0.001). Post hoc and subgroup analysis showed a superior effect of MICT over HIIT in decreasing fasting blood glucose and serum level of FGF21 (p < 0.001). Additionally, the results of the myocardial tissue qualitative analyses differed between the diabetic mouse models and the ET groups.

Conclusions: In a mouse model, type 2 diabetes can negatively affect heart tissue structure and FGF21 signaling in cardiac tissue, and both HIIT and MICT can prevent this effect. However, MICT likely more effective that HIIT in reducing circulating FGF21.