INFLUÊNCIA DO JEJUM INTERMITENTE E TREINAMENTO INTERVALADO DE ALTA INTENSIDADE SOBRE A VIA DE SINALIZAÇÃO DA AMPK E ASPECTOS MORFOLÓGICOS NO MIOCÁRDIO DE RATOS

Abstract

INTRODUCTION: High-Intensity Interval Training (HIIT) and Intermittent Fasting (IF) are non-pharmacological interventions with potential cardioprotective effects. However, the mechanisms by which HIIT and IF promote cardiac changes are not yet fully elucidated. In this context, AMP-activated protein kinase (AMPK), a fuel sensor, plays a role in cellular adaptation to nutritional and environmental stress and may exert cardioprotective effects. OBJECTIVE: To evaluate the influence of intermittent fasting and high-intensity interval training on AMPK activity and myocardial morphological aspects in rats. MATERIALS AND METHODS: Sixty Wistar rats were distributed into four groups: Control (C), Intermittent Fasting (IF), High-Intensity Interval Training (T), and Intermittent Fasting combined with High-Intensity Interval Training (TIF). At the end of 12 weeks, the animals underwent echocardiography and a maximal exercise test. After euthanasia, heavy myosin chain isoforms, morphometry, DNA fragmentation, oxidative stress markers, and the expression of proteins related to AMPK intracellular signaling and cardiac remodeling were analyzed. Statistical analysis was performed using two-way ANOVA followed by Tukey’s post hoc test. RESULTS: Regarding body composition and nutritional behavior, both interventions, as isolated factors, were associated with lower adiposity and reduced absolute mass of epididymal and retroperitoneal fat. IF reduced body mass; however, there was a significant interaction between HIIT and IF, leading to preservation of body mass in the TIF group. Concerning cardiac structure assessed in vivo, IF, as an isolated factor, reduced left ventricular chamber size, an effect attenuated by the combination with HIIT. Regarding ventricular function, IF alone improved systolic function, while HIIT altered diastolic function. For macroscopic cardiac morphology, IF reduced left ventricular mass and total heart mass in both absolute values and when normalized by tibia length (C: 0.91 ± 0.07; IF: 0.72 ± 0.08; T: 0.87 ± 0.09; TIF: 0.81 ± 0.12 g; normalized: C: 21.1 ± 1.4; IF: 17.7 ± 1.8; T: 20.8 ± 2.0; TIF: 19.7 ± 2.5 g/cm). However, the combination of HIIT and IF prevented this effect. For microscopic cardiac morphology, cross-sectional area (C: 295 ± 37; IF: 246 ± 23; T: 287 ± 19; TIF: 229 ± 35 μm²) was smaller in IF than in C and smaller in TIF than in T. Meanwhile, interstitial collagen fraction (C: 3.4 ± 0.9; IF: 2.8 ± 1.0; T: 4.5 ± 1.3; TIF: 3.3 ± 1.0%) was higher in T than in C and lower in TIF than in T. Regarding oxidative stress markers, serum malondialdehyde concentration (C: 365 ± 54; IF: 456 ± 56; T: 374 ± 47; TIF: 372 ± 36 µM) and myocardial protein carbonylation (C: 2.7 ± 0.6; IF: 5.4 ± 2.0; T: 3.2 ± 1.3; TIF: 3.0 ± 1.1 mmol/mg) were higher in IF than in C and lower in TIF than in IF. Regarding protein expression related to the AMPK signaling pathway, sestrin 1 expression (C: 1.00 ± 0.19; IF: 0.99 ± 0.42; T: 0.94 ± 0.34; TIF: 0.98 ± 0.32 arbitrary units) and sestrin 2 expression (C: 1.00 ± 0.32; IF: 0.90 ± 0.33; T: 0.96 ± 0.22; TIF: 0.91 ± 0.24 arbitrary units) were similar among groups. The p-AMPK/total AMPK ratio (C: 1.37 ± 0.78; IF: 0.57 ± 0.32; T: 1.70 ± 0.86; TIF: 1.31 ± 0.47 arbitrary units) was lower in IF than in C and higher in TIF than in T. CONCLUSION: The combination of IF and HIIT produced more favorable effects on the myocardium compared to the isolated interventions. While IF reduced heart size and AMPK activation, and HIIT increased interstitial collagen fraction, their combination preserved cardiac size, normalized AMPK activation, and restored interstitial collagen balance. Furthermore, it modulated the effects of IF on oxidative stress, favoring cardiac function maintenance and minimizing potential adverse effects.