The Effect of 8 Weeks of Endurance Training with Stevia Supplementation on the Expression of Genes (POMC and MC4R) Involved in Hypothalamic Axis Metabolism in Obese Male Wistar Rats

Obesity results from complex interactions of environment, genetic factors, and human behavior. Studies of families, adopted children, and twins have shown that 45%–75% of changes in body mass index (BMI) between individuals are due to genetic factors. The melanocortin 4 receptor (MC4R) gene is a single exon and expresses a protein receptor containing 323 amino acids. Mutations in this gene cause partial or complete loss of function of this receptor, and by disrupting the energy homeostasis system, it is the most common cause of monogenic obesity and an important component of polygenic obesity. Studies on the effect of exercise and dietary supplements on the expression of hypothalamic genes involved in appetite and obesity are limited. Therefore, this study investigated the effect of 8 weeks of endurance training with stevia supplementation on the expression of genes (POMC and MC4R) involved in hypothalamic axis metabolism in obese male Wistar rats.

In the present experimental study, 25 adult Wistar rats were divided into 5 groups. Four groups underwent a high–calorie diet to gain weight; one group followed a normal diet. The groups were as follows: exercise–obese, stevia supplement–obese, exercise and stevia supplement–obese, obese, and control. The supplement groups received stevia at a dose of 250 mg/kg body weight of rats 5 days a week for 8 weeks. The training program consisted of walking on a treadmill with an intensity of 50% to 70% oxygen consumption, which started at 15 m/min in the first week and reached a speed of 22 m/min in the eighth week. Also, in the first and last 5 minutes, walking at a speed of 10 m/min was performed to warm up and cool down, respectively. Finally, the mice were anesthetized using a combination of 70 to 30 ketamine and xylazine (the injection rate was one large syringe/100 g body weight). Tissue sampling was performed in under 90 s. Tissue was cast into microtube shield RNA after selection. Immediately after the mRNAs were fixed, they were transferred into liquid nitrogen at –180°C and sent to the laboratory. It was placed in the laboratory at –80°C, and the genes were extracted. Data were analyzed using 1–way analysis of variance (ANOVA) and LSD post hoc test by SPSS software version 19 at a significance level of 0.05.

The ANOVA showed no significant difference between the studied groups in the MC4R gene (p=0.684). But a significant difference was observed in the POMC gene (p=0.031). Based on the results of the LSD post hoc test, there was a significant difference in POMC gene expression between the obese group and the control group (p=0.003) and between the obese group and the stevia plus exercise group (p=0.015).

Based on the findings of this study, endurance training and stevia supplementation increased the expression of genes (POMC and MC4R) involved in hypothalamic axis metabolism and subsequently decreased appetite.