The effect of continuous aerobic training on Fetuin-A index and insulin sensitivity in male rats with non-alcoholic fatty liver disease

چکیده مقاله

Introduction Non-alcoholic fatty liver disease (NAFLD) is a spectrum of diseases in which hepatic steatosis is observed with or without inflammation and fibrosis. This disease can progress to cirrhosis( Jennison et al, 2018). Fetuin A is a cytokine synthesized in the liver that is associated with the development of type 2 diabetes and NAFLD in rat models. Studies have shown that increased uptake of Fetuin A inhibits protein kinase B activity in the liver and may thus affect insulin resistance (Malin et al, 2014). Injection of a single dose of Fetuin A has been shown to cause insulin resistance (Jung et al, 2019). Also, indicators such as insulin resistance and reduced insulin sensitivity are considered as the most important initial pathophysiological mechanisms in the development of fatty liver disease (Petta et al, 2009). There is credible evidence of the effect of exercise in the treatment of NAFLD and aerobic exercise has been reported to reduce Fetuin A (Malin et al, 2014). Aerobic exercise also improves insulin resistance by reducing intracellular fat and improving liver function (Hashida et al, 2017). Exercise increases the body's responsiveness to insulin by increasing glucose transporters into muscle cells and insulin receptor substrates (Azimidokht et al, 2015). Aerobic exercise has been shown to reduce Fetuin A in rats (Zandi et al, 2022). Continuous exercise is a long-term exercise, usually performed without rest (Turabi et al, 2022) and may have positive effects on the treatment, and prevention of fatty liver disease; however, the precise effect of intensity, duration, type (aerobic, resistance, combined, etc.), and mode of exercise (intermittent or continuous) on improving NAFLD is controversial (Pedersen et al, 2009). Scientists have shown that although exercise training, independent of weight loss, improves fatty liver disease, the optimal dose of exercise training and the pathological mechanisms by which سومینهمایش بین المللیچالشهای نوین علوم ورزشی)تندرستیو قهرمانی)در جاده ابریشم، ایران،تبریز،1404 3rd International Congress on New Challenges of Sport Sciences (Health and championship) on the Silk Road, Iran, Tabriz, 2025 exercise improves fatty liver disease are not precisely known (Houghton et al, 2017). Therefore, in the present study, the effect of continuous training at an intensity of 50 to 60% of maximum oxygen consumption on Fetuin A and insulin sensitivity in mice with NAFLD was investigated to clarify the effect of appropriate intensity of continuous aerobic training to help improve non- alcoholic fatty liver disease. Methods In this experimental study thirty male Wistar rats, aged six to eight weeks, with an average weight of 150 to 180 grams, were maintained under conditions of temperature (22±3 °C), light (12 hours of light and 12 hours of darkness), and humidity (about 45%). They were randomly divided into three groups (10 rats in each group) including continuous exercise, control (fatty liver disease), and healthy control (standard food). Two groups were placed on a high-fat diet to induce fatty liver disease. Then, the rats underwent continuous exercise for eight weeks, five sessions per week at an intensity of 50 to 60% of maximum oxygen consumption for 50 minutes, and were fed a high- fat diet until the end of the study. The control group (fatty liver disease) was fed a high-fat diet until the end of the study and did not participate in any exercise program. The healthy control group did not participate in any exercise program, but received standard food. 48 hours after the last training session with overnight fasting, the rats were weighed and then anesthetized. Then, by opening the animal's chest, blood samples were collected directly from the animal's heart. The fatty liver induction protocol was started for 12 weeks through a high-fat diet for all rats, except for the standard diet group, after one week of familiarization with the housing environment. It should be noted that the present study protocol was approved by the Ethics Committee of Mashhad University of Medical Sciences with the ID number IR.MUMS.MEDICAL.REC.1397.063. After one week of familiarization of the rats with training, the maximum oxygen consumption of the rats was measured, and then, a continuous training protocol with an intensity of 50 to 60% of the maximum oxygen consumption was performed on a treadmill with a zero-degree incline for 8 weeks, 5 times a week and for 50 minutes per session ( Nunes et al, 2015). Serum fetuin A concentration was measured using a Zellbio kit from Germany for animal samples (rats) with a sensitivity of 0.9 ng/ml, an internal coefficient of variation of less than 10%, and an external coefficient of variation of less than 12%. The insulin sensitivity index was calculated with the Quick index. To extract the results, the normal distribution of the data was examined using the Shapiro-Wilk test and the homogeneity of variances was examined using the Levene test, and then, a one-way analysis of variance (ANOVA) statistical test was performed. Findings According to the findings, serum fetuin A levels in the fatty liver control group were significantly reduced compared to the healthy control group, but eight weeks of continuous aerobic exercise significantly reduced serum fetuin A levels (P=0.03) and increased insulin sensitivity (P=0.01) in mice with fatty liver. سومینهمایش بین المللیچالشهای نوین علوم ورزشی)تندرستیو قهرمانی)در جاده ابریشم، ایران،تبریز،1404 3rd International Congress on New Challenges of Sport Sciences (Health and championship) on the Silk Road, Iran, Tabriz, 2025 Discussion The results of the present study are consistent with other findings that aerobic exercise training improves liver enzymes and intrahepatic fat ( Kazemi Nasab et al, 2022); significantly reduces fetuin A after aerobic exercise ( Zandi et al, 2022); and reduces the effect of aerobic exercise at an intensity of 60 to 70% of heart rate reserve on fetuin A ( Turabi et al, 2022). Our findings are also consistent with the significant increase in insulin sensitivity observed after aerobic exercise (Malin et al, 2014, Habibi Maleki et al, 2020). The findings of the present study confirm the effect of eight weeks of continuous aerobic exercise at an intensity of 50 to 60% of maximum oxygen consumption on improving insulin sensitivity and serum fetuin A levels in mice with NAFLD; however, investigating the issue in a human sample is of particular importance, so it is suggested that the effect of this type of aerobic exercise be investigated in human studies in order to provide specific and useful recommendations to patients with nonalcoholic fatty liver disease. Rrefrences Azimidokht SMA, Mogharnasi M, Kargarshouroki MK, Zarezademehrizi AA. The effect of 8 weeks interval training on insulin resistance and lipid profiles in type 2 diabetic men treated with metformin. Sport Biosciences, 2015; 7(3), 461-7. [In Persian] Elmer D. J, Laird R. H, Barberio M. 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