indices and histophatology of liver effects of eight-week high intensity interval trqining and oligopin supplementation on liver enzymes, inflammatory

چکیده مقاله

The effect of 8-week high intensity interval training and Oligopin supplementation on liver enzymes, inflammatory indices and histopathology of liver in obese male Wistar rats with non-alcoholic fatty liver disease Homa Khaleghzadeha, Zahra Kohestani sinia, Mohammad Esmaeil Afzalpoura*, Mohammad Ali Sardarb aDepartment of Sport Sciences, University of Birjand, Birjand, Iran bDepartment of Nutrition, Mashhad University of Medical Sciences, Mashhad, Iran Abstract Purpose: The liver is a vital innate immune organ with a wide range of innate immune cells. Recent studies have proved that an imbalance in liver cytokines (increase in pro-inflammatory and a decrease in anti-inflammatory cytokines) may be implicated in the development of non-alcoholic fatty liver disease (NAFLD) (1 -2). Since NAFLD is a chronic liver disease that if not treated, it would develop, it is important to adopt a proper treatment procedure for its prevention or treatment. The efficacy and immunity of drug therapy for NAFLD is not known (3-4). As the first recommendations for treatment, a healthy lifestyle, combined with a controlled diet, physical activity and exercise-related behaviors along with anti-oxidant supplementation are suggested (5). Therefore, the purpose of this study was to determine The effect of 8-week high intensity interval training and Oligopin supplementation on liver enzymes, inflammatory indices and histopathology of liver in obese male Wistar rats with non-alcoholic fatty liver disease. Method: In this experimental study, 43 adult male Wistar rats 6 weeks of age and a weight of 170 to 200 g were purchased from the animal laboratory of Medical Sciences University of Mashhad. The rats were kept in a controlled environment (an animal room) with food and water provided during the experiments with free access to water and food. Five rats were fed as a healthy group under normal diet (ND) to control and evaluate the body weight changes during the study. Also, 38 rats were under a high-fat diet (HFD) (Table 1) for 12 weeks and then seven rats were euthanized for confirmation of fatty liver (6). After 12 weeks of consuming the HFD, the 31 rats induced NAFLD were randomly divided into four groups: high-fat diet sedentary (HFD-SED, n = 7); high-fat diet and high-intensity interval training (HFD-HIIT, n = 8); high-fat diet and Oligopin (HFD-O, n = 8) and high-fat diet and high-intensity interval training plus Oligopin (HFD-HIIT + O, n = 8). They were also fed with an HFD until the end of the study. The HIIT included eight weeks, five sessions per week for 40 min per each session. The training protocol was conducted in a motorized treadmill, specially designed for rats. HIIT was performed with an 8-minuets warm up with the speed of 10 m/min, followed by four 4-minspeed intervals and the intensity of 80–95% VO2max and four 4-min slow intervals and the intensity of 50–60% VO2max (a zero-degree slope) (7). Animals in HFD-O and HFD-HIIT + O groups received 10 mg/kg/day Oligopin orally. The rats were scarified following an eight-week intervention and 48 hours after the last intervention and supplementation session which followed a night fasting. Samples of blood and body tissues were extracted. To analyze the data, one-way ANOVA and Least Significant Difference (LSD) test were applied, with p<0.05. Result: Based on the experimental results, changes to body weight gain lead to a significant increase in body weight of participant in the HDF group and synergetic inhibition effect in the Oligopin supplement and HIIT groups. Between group differences showed that at the end of 12th week, body weight was significantly higher in 4 groups of HFD recipient in comparison with ND-SED (P<0.001). At the end of 20 weeks, body weight in each of the 4 groups of HFD was more than ND-SED (P<0.001). Moreover, it is shown that body weight in HFD-HIIT + O, HFD-O, and HFD-HIIT were lower in comparison with the HFD-SED group (p<0.05). ALT increased after HFD feeding and was significantly decreased in the HFD-O, HFD-HIIT + O groups; while HIIT did not have a significant effect on ALT concentration. The combination of O and HIIT produced an additive effect on reduced ALT activity compared to O or HIIT alone. AST showed a similar pattern as ALT, except the HIIT alone causes a significant decrease in AST. For the inflammatory indices, we measured TNF-α and IL-6 plasma concentration. HFD feeding had no effect on TNF-α plasma concentration, but it significantly increased the IL-6 level in plasma concentration. The HIIT and HIIT + O treatments showed a trend for inhibition, whereas Oligopin supplement had no effect on TNF-α and IL-6 plasma concentration. The results of histopathology showed that liver condition was normal in ND-SED, HFD-HIIT AND HFD-HIIT + O groups. In these groups, the structure of liver, including liver parenchyma and portal space, remained unaltered in fatty droplets or steatosis, fbrosis and inflammation, and there was no significant change in the histopathology. However, in the HFD-O group, we observed minor steatosis, changes in macro and micro-vesicular lipids in 7–8% of hepatitis, along with minor inflammation in liver parenchyma and portal spaces. In addition, we discovered mild steatosis in the HFD-SED group, variations in micro-vesicular lipids in 40% of hepatitis, along with minor inflammation in portal spaces and minor one in liver parenchyma. Discussion and Conclusion: This study showed that the high-intensity interval training reduces the levels of pro-inflammatory cytokines such as IL-6 and TNF-α, which rise during the disease, with or without oligopine supplementation. We found that HIIT could significantly enhance the beneficial effects in HFD-induced liver dysfunctions. Together with the fact that HIIT could efficiently accelerate nutrient absorption and metabolism, we thereby proposed that HIIT could promote Oligopin absorption for increased benefits. Our results suggest that the combination of HIIT and Oligopin supplement could be an efficient strategy for treating obesity related NAFLD. Keyword: High-Intensity Interval Training, Oligopin, Inflammatory indices, Histopathology, Non-alcoholic Fatty Liver Disease References 1. Zhan YT, An W. Roles of liver innate immune cells in nonalcoholic fatty liver disease. World journal of gastroenterology: WJG. 2010 Oct 7;16(37):4652. 2. Oh S, So R, Shida T, Matsuo T, Kim B, Akiyama K, Isobe T, Okamoto Y, Tanaka K, Shoda J. High-intensity aerobic exercise improves both hepatic fat content and stiffness in sedentary obese men with nonalcoholic fatty liver disease. Scientific reports. 2017 Feb 22;7(1):1-2. 3. Conjeevaram HS, Tiniakos DG. exercise for NAFLD: does intensity matter?. American Journal of Gastroenterology. 2011 Mar 1;106(3):470-5. 4. Zelber-Sagi S, Ratziu V, Oren R. Nutrition and physical activity in NAFLD: an overview of the epidemiological evidence. World journal of gastroenterology: WJG. 2011 Aug 7;17(29):3377. 5. Johnson NA, George J. Fitness versus fatness: moving beyond weight loss in nonalcoholic fatty liver disease. Hepatology. 2010 Jul;52(1):370-80. 6. Silva RN, Bueno PG, Avó LR, Nonaka KO, Selistre-Araújo HS, Leal AM. Effect of physical training on liver expression of activin A and follistatin in a nonalcoholic fatty liver disease model in rats. Brazilian Journal of Medical and Biological Research. 2014 Sep;47(9):746-52. 7. Nunes RB, Alves JP, Kessler LP, Dornelles AZ, Stefani GP, Lago PD. Interval and continuous exercise enhances aerobic capacity and hemodynamic function in CHF rats. Brazilian journal of physical therapy. 2015(AHEAD):00-.