Different training intensities induced autophagy and histopathology appearances potentially associated with lipid metabolism in wistar rat liver

Abstract

Introduction: Aerobic training has a beneficial effect on enhancing liver functions. Autophagy might potentially play a role in preventing excessive lipid accumulation, regulating oxidative stress, and inflammation in the liver. Objective: To investigate the potential linking role of autophagy-related gene expressions and protein levels with histopathology changes in Wistar rat livers after treadmill training under different intensities. Methods: 20 rats were divided into 4 groups (control, low intensity, moderate intensity, and high intensity). 8 weeks of treadmill training was conducted with a frequency of 5 days per week, for a duration of 30 min per day. Liver histopathology was studied using hematoxylin-eosin, and oil red O staining. RNA and protein from the liver tissues were extracted to examine the autophagy-related gene (LC3, p62) and protein levels (Beclin, ATG5, LC3, p62). The gene expressions of CPT1a, CD36, FATP 2,3,5, GLUT2, and FGF21 were also studied. Results: Different intensities of training might potentially modulate autophagy-related gene expressions in rat livers. LC3 and p62 mRNA expressions in moderate and high intensities decreased compared to control. Beclin, ATG5, and LC3 protein level increased compared to control, while p62 protein level decreased compared to control. Whereas for the other genes, we found an increase in CPT1a, but we did not observed any changes in the expression of the other genes. Interestingly, autophagy-related gene expressions might be correlated with the changes of sinusoidal dilatation, cloudy swelling, inflammation, and lipid droplets of the liver tissues. Conclusion: Moderate and high intensities of training induce autophagy activity, combined with a shift in metabolic zonation in liver that might be potentially correlated with lipophagy. Our results showed the potential interplay role between autophagy and liver histopathology appearances as a part of the adaptation process to training.

Impact of Different Physical Exercises on the Expression of Autophagy Markers in Mice

“…Although other investigations regarding the effects of exercise on healthy liver demonstrated an increase in LC3II and a decrease in Sqstm1/p62, these authors did not use autophagy flux inhibitors (i.e., colchicine, chloroquine, etc.) [ 11 , 14 , 20 , 59 , 61 , 62 ]. Future investigations should evaluate these protocols’ chronic effects and their relationships with hepatic morphological adaptations, because Sqstm1/p62 deficiency was linked to diabetes and obesity development in adulthood [ 63 ].…”

“…The majority of investigations about the effects of exercise on the autophagic pathway in multiple tissues used endurance exercise protocols [ 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 ]. The type of exercise and its intensity can differently upregulate autophagy [ 20 ]. The studies evaluating the impact of strength [ 21 ] or concurrent exercise [ 22 ] on autophagy are minimal and only analyzed skeletal muscle samples.…”

New Insights into Molecular Mechanisms Mediating Adaptation to Exercise; A Review Focusing on Mitochondrial Biogenesis, Mitochondrial Function, Mitophagy and Autophagy

“…Differing intensities of exercise result in varying preferences for the main fuel source. For example, lower intensity exercise is fuelled mainly by lipids, whereas higher intensity exercise leads to glucose as the preferred fuel source [125][126][127][128]. The utilisation of lipids for an energy source is beneficial in preventing excessive accumulation of lipids within the hepatocytes, a phenomenon that is also mediated by changes in regulatory autophagy processes.…”

Exercise Serum Alters Genes Related Mitochondria in Cardiomyocyte Culture Cell

“…European Society of Cardiology heart failure guidelines recommend aerobic exercise to improve the performance capacity and cardiovascular endurance (Ponikowski et al, 2016). Taking the aerobic physical exercise in a moderate intensity for 30 minutes/day, 150 minutes/seven day, or in vigorous intensity or blend of both for 75 minutes/seven day is recommended for adults (Gunadi et al, 2020) . Physical exercise results in physiological changes in almost all body systems, including improving metabolic and cardiovascular status.…”

“…Physical exercise results in physiological changes in almost all body systems, including improving metabolic and cardiovascular status. The positive impacts of activity on the cardiovascular system are well documented (Gunadi et al, 2020;Piepoli et al, 2016).…”