Intensity-dependent effects of interval training on brain mitophagy, metabolic signaling pathways, and neuroinflammation in a rat model of type 2 diabetes.

Type 2 diabetes mellitus impairs brain metabolic and mitochondrial homeostasis, yet the intensity-dependent neuroprotective effects of exercise remain poorly defined. This study examined the intensity‑dependent effects of interval training on brain mitophagy, metabolic signaling, oxidative stress, and neuroinflammation in a type 2 diabetes model. Fifty male rats were assigned to five groups (n = 10 each): healthy control (HC), diabetic control (DC), diabetic + low-intensity interval training (LIIT), diabetic + moderate-intensity interval training (MIIT), and diabetic + high-intensity interval training (HIIT). Following the intervention, hippocampal and cortical tissues were analyzed for metabolic signaling markers (AMPK, ULK1, mTOR), mitophagy-related proteins (PINK1, Parkin, LC3-II/I, p62), oxidative and antioxidant indices (MDA, SOD, CAT, TAC), pro-inflammatory cytokines (TNF-α, IL-6, IL-1β), and lipid peroxidation (4-HNE). Statistical significance was set at p < 0.05. MIIT and HIIT activated AMPK-ULK1 signaling and suppressed mTOR in the hippocampus and cortex, leading to enhanced mitophagy, particularly in the hippocampus. These adaptations were accompanied by improved redox balance, reduced lipid peroxidation, and attenuated neuroinflammation, with effects increasing in an intensity-dependent manner (LIIT < MIIT < HIIT). Interval training may support neuroprotective adaptations in type 2 diabetes, with moderate- and high-intensity protocols potentially offering greater benefits than low intensity. Still, these effects require confirmation in broader experimental contexts.