scholarly journals Changes in rat liver fatty acid profile in experimental non-alcoholic steatohepatitis

2021 ◽  
Vol 10 (4) ◽  
pp. 206-214
Author(s):  
E. B. Shustov ◽  
A. V. Bunjat ◽  
A. G. Platonova ◽  
O. M. Spasenkova ◽  
N. V. Kirillova ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Liver Disease ◽  
Male Rats ◽  
Laboratory Animals ◽  
Carbon Chain Length ◽  
Alcoholic Fatty Liver ◽  
Morphological Form ◽  
Alcoholic Steatohepatitis ◽  
Quantitative Calculation ◽  
Δ9 Desaturase

Introduction. Non-alcoholic fatty liver disease (NAFLD) is the most common liver disease in the world. Non-alcoholic steatohepatitis (NASH), a clinically progressive morphological form of NAFLD, ranks second in the list of reasons for liver transplantation in the adult population. In the pathogenesis of this disease, metabolism and distribution of free fatty acids (FFA) play an important role. A large number of studies have established that the level of FFA in peripheral blood directly correlates with the severity of NASH, but it is still unclear what effect fluctuations in the profile of fatty acids (FA) in the liver have in steatohepatitis.Aim. Study of changes in the profile of fatty acids in the liver of laboratory animals with experimental non-alcoholic steatohepatitis.Materials and methods. The study was carried out on 17 white outbred male rats, which were randomized into two groups – intact (n = 6) and control (steatohepatitis) (n = 11). Steatohepatitis was modeled by 12-month use of a hypercaloric high-fat diet against the background of hypodynamia. The content of fatty acids in the liver was determined in the reaction of methanolysis and extraction with a hexane mixture of their methyl esters. The LC was separated by gas chromatography-mass spectrometry. Calibration for quantitative calculation was carried out with deuterated tridecanoic acid. The content of saturated and monounsaturated higher FAs, their aldehydes and hydroxy derivatives, as well as sterols were studied.Results and discussion. A total decrease in the content of FFA in the liver of animals with steatohepatitis was revealed. The most significant decrease occurred mainly in the class of monounsaturated fatty acids and cholesterol. Also, a significant decrease in the activity of Δ9-desaturase, a key enzyme in the synthesis of monounsaturated FAs from their precursor with the same carbon chain length, was revealed, which was manifested by a significant decrease in their amount in the liver. There were no statistically significant changes in the levels of aldehydes and hydroxy acids between the study groups, as well as in the level of sterols (except for cholesterol, the content of which decreased significantly).Conclusion. Thus, in the liver of rats with steatohepatitis caused by a combination of a hypercaloric diet and hypodynamia, statistically significant changes in the profile and concentration of fatty acids were found in comparison with healthy animals. The demonstrated shifts in FA composition may reflect both adaptive and pathological changes in the liver of animals with NAFLD and require further study.

scholarly journals Modification of a model of non-alcoholic fat liver disease in rats with a сombination of a hypercaloric diet and hypodynamia

2021 ◽  
Vol 10 (4) ◽  
pp. 155-165
Author(s):  
A. V. Bunjat ◽  
O. M. Spasenkova ◽  
V. E. Karev ◽  
A. V. Karavaeva ◽  
D. Ju. Ivkin ◽  
...  
Keyword(s):  
Body Weight ◽  
Liver Disease ◽  
Physical Performance ◽  
White Male ◽  
Male Rats ◽  
Laboratory Animals ◽  
Control Group ◽  
Alcoholic Fatty Liver ◽  
Epididymal Fat ◽  
Hypercaloric Diet

Introduction. Non-alcoholic fatty liver disease (NAFLD) is the most common liver disease in the world, and non-alcoholic steatohepatitis is the second most common cause of liver transplantation in the adult population. An urgent task is to find and develop an optimal model of NAFLD in laboratory animals, which would reproduce all the features of this disease in the clinic.Aim. Modification of the NAFLD model in laboratory animals (rats), which allows the obtained data to be transmitted to humans as fully as possible.Materials and methods. The study was conducted on 52 outbred white male rats of the same age. As the basis of the model, a hypercaloric high-fat diet was used with the addition of food appeal enhancers (sodium glutamate and liquid shrimp extract) and for the first-time conditions of hypodynamia were used – restriction of the motor activity of animals using specially designed cells, in which an individual 11 × 18 cm cell was allocated for each individual. The duration of the study was 12 months. In the course of the experiment, body weight, physical performance, biochemical parameters of blood serum and urine in dynamics were assessed, and lethality was recorded. After the end of the study, the mass of internal organs, visceral and epididymal fat was analyzed, and a histological examination of the liver was performed.Results and discussion. In the course of the experimental study, the development of NAFLD in rats of the control group of animals was histologically confirmed. A high mortality rate was revealed in the group of animals with pathology. Compared with animals of the intact group, a statistically significant increase in their body weight, liver weight, visceral and epididymal fat, a decrease in physical performance, disturbances in lipid, carbohydrate and protein metabolism were revealed, as well as signs of deterioration of the protein synthesis and excretory functions of the liver.Conclusion. A number of advantages of the NAFLD model with a combination of a hypercaloric diet and hypodynamic conditions were revealed, including the similarity of the conditions for the formation and pathogenesis of the disease in experimental animals and humans, which ensures the adequacy of data translation from preclinical practice to clinical practice.

Prevalence, diagnosis and treatment with 3 different statins of non-alcoholic fatty liver disease/non-alcoholic steatohepatitis in military personnel. Do genetics play a role?

2020 ◽  
Vol 18 ◽  
Author(s):  
Georgios Sfikas ◽  
Michael Psallas ◽  
Charalambos Koumaras ◽  
Konstantinos Imprialos ◽  
Evangelos Perdikakis ◽  
...  
Keyword(s):  
Liver Disease ◽  
Fatty Liver ◽  
Military Personnel ◽  
Fatty Liver Disease ◽  
Exercise Group ◽  
Severe Form ◽  
Laboratory Evaluation ◽  
Alcoholic Fatty Liver ◽  
Alcoholic Steatohepatitis ◽  
Alcoholic Fatty Liver Disease

Background: Non-alcoholic fatty liver disease (NAFLD) and its severe form, non-alcoholic steatohepatitis (NASH), are major health problems worldwide. Genetics may play a role in the pathogenesis of NAFLD/NASH. Aim: To investigate the prevalence of NAFLD/NASH in 5,400 military personnel and evaluate the effect of treatment with 3 statins on NAFLD/NASH using 2 non-invasive scores [NAFLD Activity Score (NAS); Fibrosis-4 score (FIB-4)]. Methods: During the mandatory annual medical check-up, military personnel underwent a clinical and laboratory evaluation. Participants with NAFLD/NASH were randomised to 4 groups (n=151 each): dietexercise, atorvastatin, rosuvastatin or pitavastatin for 1 year (i.e. until the next routine evaluation). Results: From all the participants, 613 had NAFLD/NASH (prevalence 11.3 vs 39.8% in the general population, p<0.001); 604 consented to participate in the study. After a year of treatment, the diet-exercise group showed no significant changes in both scores (NAS 4.98 baseline vs 5.62, p=0.07; FIB-4 3.42 vs 3.52, p=0.7). For the atorvastatin group, both scores were reduced (NAS 4.97 vs 1.95, p<0.001, FIB-4 3.56 vs 0.83, p<0.001), for rosuvastatin (NAS 5.55 vs 1.81, p<0.001, FIB-4 3.61 vs 0.79, p<0.001), and for pitavastatin (NAS 4.89 vs 1.99, p<0.001, FIB-4 3.78 vs 0.87, p<0.001). Conclusions : Atorvastatin, rosuvastatin and pitavastatin have a beneficial and safe effect in NAFLD/NASH patients as recorded by the improvement in the NAS (representing NAFLD activity) and FIB-4 (representing liver fibrosis) scores. Since both those with and without NAFLD/NASH shared several baseline characteristics, genetics may play a role in the pathogenesis of NAFLD/NASH and its treatment with statins.

scholarly journals The Role of the Histone Methyltransferase EZH2 in Liver Inflammation and Fibrosis in STAM NASH Mice

Biology ◽  
2020 ◽  
Vol 9 (5) ◽  
pp. 93 ◽  
Author(s):  
Seul Lee ◽  
Dong-Cheol Woo ◽  
Jeeheon Kang ◽  
Moonjin Ra ◽  
Ki Hyun Kim ◽  
...  
Keyword(s):  
Liver Disease ◽  
Epigenetic Modification ◽  
Treatment Options ◽  
Histone Methyltransferase ◽  
Alcoholic Fatty Liver ◽  
Alcoholic Steatohepatitis ◽  
Promising Therapeutic Target ◽  
Alcoholic Fatty Liver Disease ◽  
Potential Therapeutics

Non-alcoholic fatty liver disease (NAFLD) is a leading form of chronic liver disease, with few biomarkers and treatment options currently available. Non-alcoholic steatohepatitis (NASH), a progressive disease of NAFLD, may lead to fibrosis, cirrhosis, and hepatocellular carcinoma. Epigenetic modification can contribute to the progression of NAFLD causing non-alcoholic steatohepatitis (NASH), in which the exact role of epigenetics remains poorly understood. To identify potential therapeutics for NASH, we tested small-molecule inhibitors of the epigenetic target histone methyltransferase EZH2, Tazemetostat (EPZ-6438), and UNC1999 in STAM NASH mice. The results demonstrate that treatment with EZH2 inhibitors decreased serum TNF-alpha in NASH. In this study, we investigated that inhibition of EZH2 reduced mRNA expression of inflammatory cytokines and fibrosis markers in NASH mice. In conclusion, these results suggest that EZH2 may present a promising therapeutic target in the treatment of NASH.

scholarly journals Portal lymphadenopathy predicts non-alcoholic steatohepatitis and advanced fibrosis in non-alcoholic fatty liver disease

PLoS ONE ◽  
2018 ◽  
Vol 13 (11) ◽  
pp. e0207479 ◽  
Author(s):  
Saleh Daher ◽  
Namma Lev Cohen ◽  
Muhammad Massarwa ◽  
Mahmud Mahamid ◽  
Mira Nasser ◽  
...  
Keyword(s):  
Liver Disease ◽  
Fatty Liver ◽  
Fatty Liver Disease ◽  
Advanced Fibrosis ◽  
Alcoholic Fatty Liver ◽  
Alcoholic Steatohepatitis ◽  
Alcoholic Fatty Liver Disease

scholarly journals Hypoxia-Inducible Factors as Key Players in the Pathogenesis of Non-alcoholic Fatty Liver Disease and Non-alcoholic Steatohepatitis

2021 ◽  
Vol 8 ◽  
Author(s):  
Lorenz M. W. Holzner ◽  
Andrew J. Murray
Keyword(s):  
Transcription Factors ◽  
Liver Disease ◽  
Fatty Liver ◽  
Fatty Liver Disease ◽  
Treatment Options ◽  
Redox Homeostasis ◽  
Health Concern ◽  
Alcoholic Fatty Liver ◽  
Alcoholic Steatohepatitis ◽  
Alcoholic Fatty Liver Disease

Non-alcoholic fatty liver disease (NAFLD) and its more severe form non-alcoholic steatohepatitis (NASH) are a major public health concern with high and increasing global prevalence, and a significant disease burden owing to its progression to more severe forms of liver disease and the associated risk of cardiovascular disease. Treatment options, however, remain scarce, and a better understanding of the pathological and physiological processes involved could enable the development of new therapeutic strategies. One process implicated in the pathology of NAFLD and NASH is cellular oxygen sensing, coordinated largely by the hypoxia-inducible factor (HIF) family of transcription factors. Activation of HIFs has been demonstrated in patients and mouse models of NAFLD and NASH and studies of activation and inhibition of HIFs using pharmacological and genetic tools point toward important roles for these transcription factors in modulating central aspects of the disease. HIFs appear to act in several cell types in the liver to worsen steatosis, inflammation, and fibrosis, but may nevertheless improve insulin sensitivity. Moreover, in liver and other tissues, HIF activation alters mitochondrial respiratory function and metabolism, having an impact on energetic and redox homeostasis. This article aims to provide an overview of current understanding of the roles of HIFs in NAFLD, highlighting areas where further research is needed.

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