The effect of 8 weeks of continuous and periodic training on HNFa and STAT3 gene expression in liver tissue of male rats

STAT factors are a family of cytoplasmic proteins that are activated in response to cytokines, various growth factors as well as hormones. STAT proteins are activated by phosphorylation and then cleaved from the complex of homodimers or heterodimer receptors and transported from the cytoplasm to the nucleus, where they act by promoting specific genes that ultimately regulate gene expression. HNF is an important transcription factor that plays a very important role in the morphological and functional differentiation of the liver and also acts as a prominent factor in the differentiation of mature hepatoblasts. Studies show a significant role for HNF in liver development. It seems that intense intermittent exercise can reduce the rate of tumor progression by reducing the expression of some of the prognostic factors of angiogenesis, and an effective non-pharmacological method can be used to reduce tumor growth. According to the results of studies, limited studies have been performed on the effect of exercise with different intensities on the expression of HNF and STAT3. There is also no study that directly measures the effect of exercise on the expression of HNF and STAT3 in liver tissue. Therefore, the present study was conducted to answer this question: Is there a significant difference between the effect of three training methods with different intensities on HNF and STAT3 gene expression in the liver tissue of male Wistar rats?

The present study was approved by the ethics committee of Payame Noor University with the code IR.PNU.REC.1398.059. In terms of purpose, it is fundamental-applied, which was implemented experimentally. In the present study, 32 8-week-old male Wistar rats with an average weight of 237 ±33 g were purchased from the Pasteur Institute. After being transferred to the animal laboratory environment, these animals are housed in transparent polycarbonate cages in an environment with a temperature of 22 ± 1.4 °C, the humidity of 45 to 55%, four heads in each cage with free access to water and closed. Foods were maintained according to a 12-hour sleep-wake cycle. Animals were randomly divided into 5 groups: control group (Co) (8 heads), moderate intensity training (MIT) (8 heads), high-intensity training (HIT) (8 heads), and high-intensity interval training (HIIT) (8 heads) were divided.
The MIT protocol was performed in such a way that in the first week, 5 minutes of warm-up, 5 minutes of cooling, and 20 minutes of the main body of the exercise, including running at 65% VO2max at a speed of 20 m/min, was added to the training time every week. In the sixth week, the training time reached 37 minutes and remained constant until the end of the eighth. Also, the training speed was unchanged from the first week to the eighth week and was equal to 20 meters per minute. The HIT protocol in the first week included: 5 minutes of warm-up, 5 minutes of cooling, and 20 minutes of running training with 65% VO2max at a speed of 20 m/min and an increasing slope of the treadmill. The training time was increased every week, so that in the sixth week the training time reached 30 minutes and remained constant until the end of the eighth. On the other hand, the slope of the strip was 2% in the first and second weeks and 2% was added to the slope every 2 weeks to reach 8% in the seventh and eighth weeks. Also, the training speed from the first week to the eighth week was 20 meters per minute and was kept constant. The HIIT protocol also included 10 minutes of warm-up before the workout, in the first to fourth weeks including 3 intense intermittent runs with an intensity of 90 to 100% VO2max and a speed of 30 meters per minute in 4 minutes and 3 low-intensity intermittent runs. With 50 to 60% VO2max and at a speed of 20 meters per minute in 3 minutes. From the fifth to the eighth week, it also includes 4 intense intermittent runs with an intensity of 90 to 100% VO2max at a speed of 30 meters per minute in 4 minutes and 3 low-intensity intermittent runs with 50 to 60% VO2max at a speed of 20 meters per minute. It took 3 minutes. The main body time of the exercise was 28 minutes per repetition. Mice in the control group did not participate in any exercise program but were placed on a stationary treadmill for 10 to 15 minutes per session to adapt to the environment to create the same conditions. After in vitro analysis of the samples, descriptive statistics including standard mean and standard deviation and inferential statistics were used to quantitatively describe the data. First, the Shapirovilk test was used to determine the normality of data distribution, and the Leven test was used to determine the homogeneity of variance. Due to the normal distribution of data, parametric tests including one-way analysis of variance and Tukey's post hoc test were used at a significance level of p≥0.05.

The results of the Tukey post hoc test showed that there was no significant difference in STAT3 gene expression in the liver tissue of male Wistar rats between MIT and HIT groups compared to the HIIT group. There is a gap between the HIIT and control groups. The results also showed that there was a significant difference in the expression of the HNFα gene between MIT, HIT, and control groups compared to the HIIT group.

The results showed that intense intermittent training compared to other training intensities leads to a greater decrease in STAT3 gene expression and a further increase in HNFa expression, so the use of this training method is recommended in the development of liver tissue function.