Changes in rat liver fatty acid profile in experimental non-alcoholic steatohepatitis
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 pathogenesi...
| Main Authors: | , , , , , , , |
|---|---|
| Format: | Article |
| Language: | Russian |
| Published: |
LLC Center of Pharmaceutical Analytics (LLC «CPHA»)
2021-12-01
|
| Series: | Разработка и регистрация лекарственных средств |
| Subjects: | |
| Online Access: | https://www.pharmjournal.ru/jour/article/view/1121 |
| _version_ | 1826569661376888832 |
|---|---|
| author | E. B. Shustov A. V. Bunjat A. G. Platonova O. M. Spasenkova N. V. Kirillova D. Yu. Ivkin S. V. Okovityi A. N. Kimaev |
| author_facet | E. B. Shustov A. V. Bunjat A. G. Platonova O. M. Spasenkova N. V. Kirillova D. Yu. Ivkin S. V. Okovityi A. N. Kimaev |
| author_sort | E. B. Shustov |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-10T01:38:42Z |
| format | Article |
| id | doaj.art-035cfcee0b7a412e9bdb6ac600dc60c9 |
| institution | Directory Open Access Journal |
| issn | 2305-2066 2658-5049 |
| language | Russian |
| last_indexed | 2025-03-14T11:42:53Z |
| publishDate | 2021-12-01 |
| publisher | LLC Center of Pharmaceutical Analytics (LLC «CPHA») |
| record_format | Article |
| series | Разработка и регистрация лекарственных средств |
| spelling | doaj.art-035cfcee0b7a412e9bdb6ac600dc60c92025-03-02T09:53:26ZrusLLC Center of Pharmaceutical Analytics (LLC «CPHA»)Разработка и регистрация лекарственных средств2305-20662658-50492021-12-0110420621410.33380/2305-2066-2021-10-4(1)-206-214927Changes in rat liver fatty acid profile in experimental non-alcoholic steatohepatitisE. B. Shustov0A. V. Bunjat1A. G. Platonova2O. M. Spasenkova3N. V. Kirillova4D. Yu. Ivkin5S. V. Okovityi6A. N. Kimaev7Institute of Toxicology Federal Medical Biological Agency of Russia; Saint Petersburg State Chemical and Pharmaceutical UniversityV. A. Almazov NMRCSaint Petersburg State Chemical and Pharmaceutical UniversitySaint Petersburg State Chemical and Pharmaceutical UniversitySaint Petersburg State Chemical and Pharmaceutical UniversitySaint Petersburg State Chemical and Pharmaceutical UniversitySaint Petersburg State Chemical and Pharmaceutical UniversitySaint Petersburg State Chemical and Pharmaceutical UniversityIntroduction. 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.https://www.pharmjournal.ru/jour/article/view/1121fatty acidssterolssteatohepatitisnon-alcoholic fatty liver diseasegas chromatography-mass spectrometryhypercaloric diethypodynamia |
| spellingShingle | E. B. Shustov A. V. Bunjat A. G. Platonova O. M. Spasenkova N. V. Kirillova D. Yu. Ivkin S. V. Okovityi A. N. Kimaev Changes in rat liver fatty acid profile in experimental non-alcoholic steatohepatitis Разработка и регистрация лекарственных средств fatty acids sterols steatohepatitis non-alcoholic fatty liver disease gas chromatography-mass spectrometry hypercaloric diet hypodynamia |
| title | Changes in rat liver fatty acid profile in experimental non-alcoholic steatohepatitis |
| title_full | Changes in rat liver fatty acid profile in experimental non-alcoholic steatohepatitis |
| title_fullStr | Changes in rat liver fatty acid profile in experimental non-alcoholic steatohepatitis |
| title_full_unstemmed | Changes in rat liver fatty acid profile in experimental non-alcoholic steatohepatitis |
| title_short | Changes in rat liver fatty acid profile in experimental non-alcoholic steatohepatitis |
| title_sort | changes in rat liver fatty acid profile in experimental non alcoholic steatohepatitis |
| topic | fatty acids sterols steatohepatitis non-alcoholic fatty liver disease gas chromatography-mass spectrometry hypercaloric diet hypodynamia |
| url | https://www.pharmjournal.ru/jour/article/view/1121 |
| work_keys_str_mv | AT ebshustov changesinratliverfattyacidprofileinexperimentalnonalcoholicsteatohepatitis AT avbunjat changesinratliverfattyacidprofileinexperimentalnonalcoholicsteatohepatitis AT agplatonova changesinratliverfattyacidprofileinexperimentalnonalcoholicsteatohepatitis AT omspasenkova changesinratliverfattyacidprofileinexperimentalnonalcoholicsteatohepatitis AT nvkirillova changesinratliverfattyacidprofileinexperimentalnonalcoholicsteatohepatitis AT dyuivkin changesinratliverfattyacidprofileinexperimentalnonalcoholicsteatohepatitis AT svokovityi changesinratliverfattyacidprofileinexperimentalnonalcoholicsteatohepatitis AT ankimaev changesinratliverfattyacidprofileinexperimentalnonalcoholicsteatohepatitis |