Changes in rat liver fatty acid profile in experimental non-alcoholic steatohepatitis-Reference-Cited by-同舟云学术

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

Published:2021-12-25 Issue:4 Volume:10 Page:206-214
ISSN:2658-5049
Container-title:Drug development & registration
language:
Short-container-title:Razrabotka i registraciâ lekarstvennyh sredstv

Author:

Shustov E. B.¹^ORCID,Bunjat A. V.²^ORCID,Platonova A. G.³^ORCID,Spasenkova O. M.³^ORCID,Kirillova N. V.³^ORCID,Ivkin D. Yu.³^ORCID,Okovityi S. V.³^ORCID,Kimaev A. N.³^ORCID

Affiliation:

1. Institute of Toxicology Federal Medical Biological Agency of Russia; Saint Petersburg State Chemical and Pharmaceutical University

2. V. A. Almazov NMRC

3. Saint Petersburg State Chemical and Pharmaceutical University

Abstract

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.

Publisher

Center of Pharmaceutical Analytics Ltd

Subject

Drug Discovery,Pharmaceutical Science

Reference20 articles.

1. Lazebnik L. B., Golovanova E. V., Turkina S. V., Raikhelson K. L., Okovityy S. V., Drapkina O. M., Maev I. V., Martynov A. I., Roitberg G. E., Khlynova O. V., Abdulganieva D. I., Alekseenko S. A., Ardatskaya M. D., Bakulin I. G., Bakulina N. V., Bueverov A. O., Vinitskaya E. V., Volynets G. V., Eremina E. Yu., Grinevich V. B., Dolgushina A. I., Kazyulin A. N., Kashkina E. I., Kozlova I. V., Konev Yu. V., Korochanskaya N. V., Kravchuk Yu. A., Li E. D., Loranskaya I. D., Makhov V. M., Mekhtiev S. N., Novikova V. P., Ostroumova O. D., Pavlov Ch. S., Radchenko V. G., Samsonov A. A., Sarsenbaeva A. S., Sayfutdinov R. G., Seliverstov P. V., Sitkin S. I., Stefanyuk O. V., Tarasova L. V., Tkachenko E. I., Uspensky Yu. P., Fominykh Yu. A., Khavkin A. I., Tsyganova Yu. V., Sharhun O. O. Non-alcoholic fatty liver disease in adults: clinical picture, diagnosis, treatment. Guidelines for therapists, third version. Eksperimental’naya i klinicheskaya gastroenterologiya = Experimental and Clinical Gastroenterology. 2021;(1):4–52. (In Russ.) DOI: 10.31146/1682-8658-ecg-185-1-4-52.

2. European Association for the Study of the Liver (EASL), European Association for the Study of Diabetes (EASD), European Association for the Study of Obesity (EASO). EASL–EASD–EASO clinical practice guidelines for the management of non-alcoholic fatty liver disease. Journal of Hepatology. 2016;64(6):1388–1402. DOI: 10.1016/j.jhep.2015.11.004.

3. Chalasani N., Younossi Z., Lavine J. E., Charlton M., Cusi K., Rinella M., Harrison S. A., Brunt E. M., Sanyal A. J. The diagnosis and management of nonalcoholic fatty liver disease: practice guidance from the American Association for the study of liver diseases. Hepatology. 2018;67(1):328–57. DOI: 10.1002/hep.29367.

4. Drapkina O. M., Ivashkin V. T. Epidemiological features of non-alcoholic fatty liver disease in Russia (results of an open multicenter prospective observation study DIREGL 01903). Rossijskij zhurnal gastroenterologii, gepatologii, koloproktologii = Russian Journal of Gastroenterology, Hepatology, Coloproctology. 2014;24(4):32–38. (In Russ.)

5. Saponaro C., Gaggini M., Carli F., Gastaldelli A. The subtle balance between lipolysis and lipogenesis: a critical point in metabolic. Homeostasis. Nutrients. 2015;7(11):9453–9474. DOI: 10.3390/nu7115475.