The effect of aerobic exercise and ethanolic extract of bitter orange peel on cardioprotective genes expression in female rats fed a high-fat diet

The present study evaluates the effects of aerobic exercise and ethanolic bitter orange peel extract on the expression of cardioprotective genes in female rats fed a high-fat diet (HFD). From the Islamic Azad University's Central Tehran Branch animal facility, 30 adult female rats of the Wistar strain were randomly assigned to five groups (six rats per group): 1) normal diet control (ND-C), 2) HFD control (HFD-C), 3) HFD aerobic exercise (HFD-AE), 4) HFD ethanolic bitter orange peel extract (HFD-BP), and 5) HFD aerobic exercise and ethanolic bitter orange peel extract (HFD-AE-BP). A normal diet was supplemented with 20% palm oil, 1.5% cholesterol, and 0.25 cholic acid to induce obesity. Before the intervention, the subjects received a HFD for four weeks, then continued it for another four weeks during the intervention. During the four-week aerobic exercise protocol, treadmill running was performed at a moderate intensity. An ethanol extract of bitter orange peel was administered orally to rats at a dose of 100 milligrams per kilogram of body weight for four weeks. After euthanasia, left ventricle myocardium was collected for real-time PCR analysis of CTRP9, LKB1, and AMPK gene expression. In the HFD-C, CTRP9 (P=0.001), LKB1 (P=0.001), and AMPK (P=0.001) genes were significantly lower than in the ND-C. Aerobic exercise significantly increased their expression compared with the HFD-C (P=0.001). Comparing HFD-C with ethanolic bitter orange peel extract, ethanolic bitter orange peel extract increased gene expression significantly (P=0.001). This indicates that the simultaneous use of these two interventions was able to add up the effects of each and did not have a synergistic effect. However, since the magnitude of change when these two interventions were combined was greater than the effect of each alone, the combination of AE and BP was greater than the effect of each alone, suggesting that these two interventions may be used to mitigate cardiac complications under HFD conditions.