Type 2 diabetes mellitus (T2DM) is a prevalent metabolic disorder characterized by hyperglycemia, insulin resistance, and dysregulated hepatokine secretion. Lifestyle-based interventions, particularly those combining exercise training and intermittent fasting, have gained attention for their potential to modulate hepatokines and enhance metabolic health. This study investigated the effects of combined training and intermittent fasting on hepatic fetuin-A, chemerin-like protein chemotaxin 2 (LECT2), selenoprotein P, tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), and insulin resistance in a T2DM rat model.

Thirty-six male Wistar rats were randomly assigned to five groups: healthy control, diabetic control, intermittent fasting (IF), combined training (CT), and combined training with intermittent fasting (CT+IF). Type 2 diabetes was induced using streptozotocin and nicotinamide. The interventions were conducted over eight weeks and included moderate-intensity treadmill running and ladder-based resistance training, while the IF and CT+IF groups followed a 16:8 fasting regimen twice per week. After the intervention, serum glucose, insulin, and HOMA-IR were assessed, and hepatic expression of fetuin-A, LECT2, selenoprotein P, TNF-α, and IL-6 was determined using biochemical assays and Western blotting. Data were analyzed by one-way ANOVA followed by LSD post hoc tests.

Results showed that fetuin-A, selenoprotein P, insulin, and body weight did not differ significantly between groups. However, CT+IF significantly decreased LECT2, glucose, HOMA-IR, TNF-α, and IL-6. These findings highlight the synergistic benefits of combining exercise training with intermittent fasting as an effective non-pharmacological strategy for improving inflammation, hepatokine regulation, and insulin sensitivity in type 2 diabetes.