The Effect of Interval Aerobic Exercise Combined with Nano-emulsified Betaine Supplementation on the Genes Expression of mTORC1, PI3K, and Calcineurin in Hepatocytes of Obese Rats

Background and Purpose: Obesity is one of the major health problems in today's societies, which is associated with a wide range of diseases, including diabetes, metabolic disorders, and fatty liver. The increasing prevalence of obesity and sedentary lifestyles and the development of related diseases have led to the emergence of regular exercise as the basis for obesity treatment. Recent evidence also suggests that betaine consumption may be effective in improving obesity by affecting hepatic lipid and glucose metabolism. Therefore, in the present study, the effect of interval aerobic exercise combined with nano-emulsified betaine supplementation on the genes expression of mammalian target of rapamycin complex-1 (mTORC1), phosphatidyl inositol-3 kinase (PI3K), and calcineurin in hepatocyte cells of obese rats was investigated.
Materials and Methods: In this experimental study, 25 male Wistar rats were divided into five groups (five rats in each group): 1- healthy, 2- obese, 3- obese + supplement, 4- obese + exercise, 5- obese + supplement + exercise. Obese samples were fed a high-fat and cholesterol diet for 12 weeks. Moderate-intensity interval aerobic training was performed for 8 weeks, including treadmill running for 30 minutes, 5 days a week, with gradual overload; the training protocol in the first week included 10 1-minute activity intervals (at a speed of 10 meters per minute) with 2-minute rest intervals (at a speed of 5 meters per minute), and the running speed in the activity intervals reached 16 meters per minute in the fourth to eighth weeks. High-amplitude ultrasound was used to prepare betaine nanoemulsion, which increases its serum stability and bioavailability. Nanoemulsified betaine supplement was administered by gavage at a dose of 50 mg/kg body weight before exercise. At the end of the study period, the expression of mTORC1, PI3K, and calcineurin genes in the liver was measured by Real-Time PCR, and the data were analyzed by independent t-tests, two-way ANOVA, and Bonferroni post hoc test at a significance level of P≤0.05.
Results: Obesity significantly decreased mTORC1 and PI3K and also increased calcineurin (P=0.0001). Interval aerobic exercise significantly increased mTORC1 and PI3K and significantly decreased calcineurin (P=0.0001). Betaine supplementation also increased mTORC1 (P=0.002) and PI3K (P=0.0001) levels and decreased calcineurin (P=0.0001). Also, a statistically significant effect was observed in the interaction of exercise and supplementation on mTORC1 (P=0.0001), PI3K (P=0.0001) and calcineurin (P=0.021) levels.
Conclusion: It seems that moderate-intensity interval aerobic exercise and betaine supplementation, independently and together, may play an important role in improving obesity-induced fatty liver by affecting the expression of mTORC1, PI3K, and calcineurin genes through regulating hepatic fat metabolism.