scholarly journals Dynamics of Pro- and Anti-inflammatory Cytokines in Experimental Animals with Non-alcoholic Fatty Liver Disease Under Conditions of Hypobaric Hypoxia

2021 ◽  
Vol 9 (A) ◽  
pp. 822-826
Author(s):  
Nurgul Toktogulova ◽  
Rustam Tukhvatshin ◽  
Elmira Mainazarova
Keyword(s):  
Inflammatory Cytokines ◽  
Fatty Liver Disease ◽  
Hypobaric Hypoxia ◽  
Alcoholic Fatty Liver ◽  
Experimental Animals ◽  
Tnf Α ◽  
Low Altitude ◽  
Anti Inflammatory ◽  
Lipid Spectrum ◽  
Alcoholic Fatty Liver Disease

AIM: The aim of the study was to study the level of pro- and anti-inflammatory cytokines, tumor necrosis factor-alpha (TNF-α), and interleukin 4 (IL-4), on a model of non-alcoholic fatty liver disease (NAFLD) in experimental animals under conditions of low mountains and hypobaric hypoxia. METHODS: The study was carried out on 180 male Wistar rats, which were divided into control and experimental groups. The rats of the control group were on a standard diet. NAFLD was modeled by keeping animals on a diet (Ackermann et al., 2005) rich in fructose and fat in conditions of low mountains and hypobaric hypoxia (in a pressure chamber 6000 m above sea level) for 35 and 70 days. Total cholesterol (TC) and lipid spectrum, pro- and anti-inflammatory cytokines were determined in all groups of animals. RESULTS: The activity of pro- and anti-inflammatory cytokines in the main group during the rise of animals in the pressure chamber increased statistically significantly on the 35th day in comparison with the low-altitude group by more than 2 times, and on the 70th day of staying at the high-altitude did not have convincing differences from the low-altitude group. The cytokine index (TNF-α/IL-4) of animals in conditions of hypobaric hypoxia on a fructose enriched diet increased by more than 1.5 times after 5 weeks, staying at an altitude for 10 weeks led to a decrease of TNF-α/IL-4 in relation to the low-mountain group, in which the opposite picture was observed - a tendency towards an increase in TNF-α/IL-4. IL-4 and TNF-α _levels were statistically significantly correlated with lipid metabolism disorders. CONCLUSION: NAFLD in animals on a special diet enriched with fructose under conditions of hypobaric hypoxia leads to deeper disturbances in the system of pro- and anti-inflammatory cytokines and the lipid spectrum.

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

2021 ◽  
Vol 9 (A) ◽  
pp. 1092-1096
Author(s):  
Nurgul Toktogulova ◽  
Rustam Tuhvatshin
Keyword(s):  
Liver Disease ◽  
Fatty Liver ◽  
High Altitude ◽  
Inflammatory Cytokines ◽  
Fatty Liver Disease ◽  
Alcoholic Fatty Liver ◽  
Experimental Animals ◽  
Low Altitude ◽  
Anti Inflammatory ◽  
Alcoholic Fatty Liver Disease

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.

scholarly journals Prevention of Non-Alcoholic Fatty Liver Disease by Fruits and Vegetables Supplementation in Mice is Associated with Their Antioxidant Property

2020 ◽  
Vol 4 (Supplement_2) ◽  
pp. 1523-1523
Author(s):  
Weimin Guo ◽  
Dayong Wu ◽  
Lijun Li ◽  
Edwin Ortega ◽  
Yankun Liu ◽  
...  
Keyword(s):  
Fatty Liver Disease ◽  
Fruits And Vegetables ◽  
De Novo ◽  
Liver Steatosis ◽  
Antioxidant Property ◽  
High Fat ◽  
Alcoholic Fatty Liver ◽  
Freeze Dried ◽  
Tnf Α ◽  
Alcoholic Fatty Liver Disease

Abstract Objectives Previously we showed that supplementing a high fat diet (HFD) with a freeze-dried powder of 24 commonly consumed fruits and vegetables (F&V) prevented HFD-induced non-alcoholic fatty liver disease (NAFLD). Since the experimental diets were isocaloric with major difference being in their antioxidant content, we hypothesized that the observed effects of F&V maybe due to their antioxidant property resulting in reduced formation of inflammatory cytokines and lipids such as TNF-α and sphingolipid ceramides. Both TNF-α and ceramides have been implicated as risk factors for NFALD. The objective of this study was to test the above hypothesis. Methods Six-wk-old male C57BL/6 J mice were randomized to three groups (12/group) to receive one of the following diets: low fat (LF, 10% kcal fat), high fat (HF, 45% kcal fat), and HF plus 15% freeze-dried mixture of F&V (HF + F&V). After 20 weeks, mice were euthanized, blood and liver samples were collected for analyses of cytokines, lipids, and malondialdehyde (MDA), a lipid peroxidation biomarker, and pathways involved in ceramide formation. Results Mice fed the HF diet had significantly higher liver steatosis and plasma and/or liver ceramides, TNF-α, and MDA compared to those fed the LF diet. However, F&V supplementation prevented HF diet-induced NAFLD and significantly reduced upregulated TNF-α, ceramide, and MDA levels. Because of key role of ceramides in NFALD development, we further determined the mechanism of F&V-induced decrease in ceramide formation focusing on de novo synthesis and activity of sphingomyelinase (SMase), the enzyme that hydrolyzes sphingomyelin to generate ceramide and is modulated by oxidative stress. There was no difference in de novo ceramide synthesis; however, F&V supplementation significantly prevented HF-induced higher SMase activity. Further, liver MDA levels were positively correlated with levels of ceramides, TNF-α, SMase activity, and liver steatosis area. Conclusions The results from this study suggest that prevention of NFALD by F&V might be mediated through reduction in oxidative stress, consequently suppressing production of pro-inflammatory cytokines, and inhibiting SMase activity that leads to reduction of ceramide levels. Funding Sources This study was supported by the U.S. Department of Agriculture – Agricultural Research Service (ARS), under Agreement No. 58-1950-4-003.

scholarly journals BabaoDan attenuates high-fat diet-induced non-alcoholic fatty liver disease via activation of AMPK signaling

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Dandan Sheng ◽  
Shanmin Zhao ◽  
Lu Gao ◽  
Huifei Zheng ◽  
Wenting Liu ◽  
...  
Keyword(s):  
Liver Disease ◽  
High Fat Diet ◽  
Fatty Liver Disease ◽  
Density Lipoprotein ◽  
High Fat ◽  
Adipose Tissues ◽  
Alcoholic Fatty Liver ◽  
Ampk Signaling ◽  
Tnf Α ◽  
Alcoholic Fatty Liver Disease

Abstract Background Babaodan (BBD), a traditional Chinese medicine, has been shown to have protective effects during liver injury and ameliorate liver disease progression, but little is known about its effect on non-alcoholic fatty liver disease (NAFLD). The aim of this study was to investigate the effects of BBD on obesity-induced NAFLD. Methods C57BL/6 J mice were fed with normal diet, high fat diet (HFD) or HFD + BBD for 8 weeks. Weights of all mice were recorded every 3 days. At the end of the experiments, the level of livers, kidneys and adipose tissues of each animal was weighed. Blood serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), total cholesterol (TC), triglyceride (TG), high density lipoprotein cholesterol (HDL-C) cholesterol, low density lipoprotein cholesterol (LDL-C), glucose and leptin were detected with appropriate test kits. Haematoxylin–eosin (HE), Masson trichrome and Oil Red O staining of the liver were performed. We applied immunohistochemical analysis to investigate the expression of TNF-α, IL-6 and leptin in liver tissue. The expression of genes related lipid anabolism (SREBP1-c, ACC, SCD-1, LXRα and CD36) and ß-oxidation (CPT-1 and PPARα) in liver and adipose tissues was determined by RT-PCR. The expression of AMPK and p-AMPK was determined by western blot analysis. Results We found the weight of bodies and tissues (retroperitoneal fat pads, kidneys and livers) of mice fed with HFD + BBD were significantly lower than that of HFD-fed mice. And liver injury induced by HFD was relieved in mice treated with BBD, accompanied with significant reduction were observed in serum ALT/AST activities and alleviated pathological damage. The levels of glucose, TG, TC, HDL-C and LDL-C in the liver or serum were significantly decreased on HFD + BBD group compared with HFD group. Furthermore, BBD treatment reduced the level of TNF-α and IL-6 induced by HFD. The level of leptin in the liver and serum were reduced in mice fed with HFD + BBD than that of HFD-fed mice. Several lipid synthesis genes (SREBP1-c, ACC, SCD-1, LXRα and CD36) were down-regulated and that of ß-oxidation (CPT-1 and PPARα) up-regulated in HFD + BBD group compared with HFD group. In addition, BBD increased the expression of p-AMPK compared with untreated HFD group, which suggested BBD improved the activation of AMPK pathway. Conclusion In summary, our results indicate that BBD has potential applications in the prevention and treatment of NAFLD, which may be closely related to its effect on lipid metabolism via activation of AMPK signaling.

scholarly journals LPS-induced TNF-α factor mediates pro-inflammatory and pro-fibrogenic pattern in non-alcoholic fatty liver disease

Oncotarget ◽  
2015 ◽  
Vol 6 (39) ◽  
pp. 41434-41452 ◽  
Author(s):  
Sara Ceccarelli ◽  
Nadia Panera ◽  
Marco Mina ◽  
Daniela Gnani ◽  
Cristiano De Stefanis ◽  
...  
Keyword(s):  
Liver Disease ◽  
Fatty Liver ◽  
Fatty Liver Disease ◽  
Alcoholic Fatty Liver ◽  
Tnf Α ◽  
Alcoholic Fatty Liver Disease

scholarly journals Frequency and risk factors associated with non-alcoholic fatty liver disease in patients with type 2 diabetes mellitus

2010 ◽  
Vol 54 (4) ◽  
pp. 362-368 ◽  
Author(s):  
Vera S. G. Ferreira ◽  
Ricardo B. Pernambuco ◽  
Edmundo P. Lopes ◽  
Clarice N. Morais ◽  
Marbiana C. Rodrigues ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Risk Factors ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Uric Acid ◽  
Fatty Liver Disease ◽  
Alcoholic Fatty Liver ◽  
Tnf Α ◽  
Alcoholic Fatty Liver Disease

OBJECTIVE: To evaluate the frequency of non-alcoholic fatty liver disease (NAFLD) in patients with type 2 diabetes mellitus (DM2) and to describe its risk factors. SUBJECTS AND METHODS: Blood samples of 78 patients were collected for assessment of glycemic and lipid profile, liver enzymes, TNF-α and HOMA-IR. The diagnosis of NAFLD was established by ultrasound. RESULTS: NAFLD was observed in 42% of patients who had greater BMI (p < 0.001), and frequency of hypertension (p < 0.001). Metabolic syndrome was more frequent in those with NAFLD (p = 0.019). The levels of aspartate, alanine aminotransferase, γ-glutamyl transpeptidase, uric acid, TNF-α, insulin and HOMA-IR were significantly higher in patients with NAFLD than those without NAFLD. CONCLUSION: Almost half of patients with DM2 were found to have NAFLD, and they have more elevated BMI, as well as higher levels of aminotransferases, γ-GT, uric acid, TNF-α, insulin and HOMA-IR than subjects without NAFLD.

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