Features of the Course of Non-alcoholic Fatty Liver Disease in Experimental Animals at High Altitudes

Abstract

Background: Nearly 25% of adults worldwide are affected by non-alcoholic fatty liver disease (NAFLD). taged changes in the liver from steatosis progress to non-alcoholic steatohepatitis (NASH) and its complicated forms such as fibrosis, cirrhosis, and hepatocellular carcinoma. There are very few data in the literature on the development of NAFLD in conditions of high altitude. There are no data on the state of pro- and anti-inflammatory cytokines in NAFLD in high altitude conditions. Thus, simulating NAFLD on animals in artificial highlands will help find answers to these questions.
 Aim: to study the features of the course of non-alcoholic fatty liver disease (NAFLD) in experimental animals in artificial high-mountain conditions.
 Material and methods: The study was carried out on 180 male Wistar rats. 7 groups of experimental animals were formed, which were divided into control and experimental groups. The rats of the control group were on a standard diet. Non-alcoholic fatty liver disease was modeled by keeping animals on a diet (Ackermann et al., 2005) rich in fructose and fat in low and high mountain conditions (in a pressure chamber 6000 m above sea level) for 35 and 70 days. In all groups of animals, the following was determined: the concentration of total bilirubin (TB), the activity of the enzymes aspartate aminotransferase (AST), alanine aminotransferase (ALT), the level of total cholesterol (TC), low-density lipoprotein cholesterol (LDL), the total protein content in plasma (TP), pro- and anti-inflammatory cytokines.
 Results: In animals on a diet enriched with fructose and fat, it equally led to the inhibition of the synthetic function of the liver, both in high altitude and in low altitudes. Liver enzyme levels were uncertain. AST levels were high in all major groups, with a similar upward trend at 5 and 10 weeks on the fructose-fortified diet. The greatest shift was observed on the part of ALT in animals under conditions of hypobaric hypoxia, the growth of which was statistically significantly lower than in the low- altitude groups. The opposite picture was observed in pigment metabolism. Indicators of total cholesterol and LDL increased almost twofold in the main high- altitude groups, and were significantly higher than the indicators of low- altitude animals with p <0.001. The activity of pro- and anti-inflammatory cytokines in the main group, when the animals were raised in the pressure chamber, statistically significantly increased after 5 weeks compared to the low-altitude group by more than 2 times and statistically significantly correlated with cytolysis syndromes, hypercholesterolemia and impaired synthetic function against the background of liver hypoergosis.
 Conclusion: Non-alcoholic fatty liver disease in animals on a special diet enriched with fructose under conditions of hypobaric hypoxia is characterized by deeper violations of pigment metabolism, pro- and anti-inflammatory cytokines and lipid spectrum with simultaneously statistically significant low alanine aminotransferase indices compared to low-altitude groups on an identical diet.