Background. Obesity is a spreading disease that can lead to various heart diseases. Performing aerobic exercises and taking antioxidant supplements can prevent the pathological conditions of heart disease. Therefore, this research aimed to study the effect of aerobic exercise and consumption of pomegranate peel extract alone or in combination with each other on the expression of PI3K and MTOR genes related to cardiac hypertrophy in obese female rats. Methods. In this experimental study, 30 female Wistar rats with an average weight of 180 ± 20 g were randomly divided into healthy control, obese control, obese + extract, obese + exercise, and obese + exercise + extract. The aerobic training program reached 50% VO2max and 65% VO2max in the first and last weeks, respectively. The rats were fed with the pomegranate peel extract by gavage at 60 mg per kg of body weight. Results. Although there was a significant difference in the heart weight of rats in the exercise group compared to other groups (P < 0.05), no significant difference was observed in the expression of PI3K genes between the studied groups. However, the exercise intervention could significantly increase the expression of the mTOR gene in comparison with the other obese groups. Conclusion. Despite the significant increase in heart weight in the exercise group and the combination of exercise and extract, no significant change was observed in the PI3K gene expression after exercise and consumption of the pomegranate peel extract, but mTOR gene expression. After exercise intervention, there was a significant difference compared to non-exercise groups, which is probably one of the mechanisms involved in heart hypertrophy. Therefore, it seems that to obtain stronger results on the effects of both PI3K and mTOR genes, other factors such as training conditions, including duration, intensity, number of repetitions, recovery time, and conditions of subjects, should also be taken into consideration. In addition, the conditions of taking antioxidant supplements, for example, their duration or dosage, should be studied more. Practical Implications. Cardiac complications caused by obesity can probably be prevented with proper exercise and an effective dose of the pomegranate peel extract.
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