gastro-jРоссийский журнал гастроэнтерологии, гепатологии, колопроктологииRussian Journal of Gastroenterology, Hepatology, Coloproctology1382-43762658-6673«Gastro» LLC10.22416/1382-4376-2020-30-2-15-25gastro-j-446Research ArticleОБЗОРЫREVIEWSМетаболические и генетические детерминанты нарушения липидного обмена при неалкогольной жировой болезни печениMetabolic and Genetic Determinants of Lipid Metabolism Disruption in Non-Alcoholic Fatty Liver Diseasehttps://orcid.org/0000-0001-5018-0271КытиковаО. Ю.KytikovaO. Yu.

Кытикова Оксана Юрьевна — доктор медицинских наук, научный сотрудник лаборатории восстановительного лечения

690105, г. Владивосток, ул. Русская, 73-г.

Oksana Yu. Kytikova — Dr. Sci. (Med.), Researcher, Laboratory for Rehabilitation Treatment

690105, Vladivostok, Russkaya str., 73g.

kytikova@yandex.ruhttps://orcid.org/0000-0002-6058-201XНовгородцеваТ. П.NovgorodtsevaT. P.

Новгородцева Татьяна Павловна — доктор биологических наук, профессор, зам. директора по научной работе, главный научный сотрудник лаборатории биомедицинских исследований

690105, г. Владивосток, ул. Русская, 73-г.

Tatyana P. Novgorodtseva — Dr. Sci. (Med.), Prof., Deputy Director for Research, Chief Researcher, Laboratory for Biomedical Research,

690105, Vladivostok, Russkaya str., 73g.

nauka@niivl.ruhttps://orcid.org/0000-0003-4130-8899ДенисенкоЮ. К.DenisenkoYu. K.

Денисенко Юлия Константиновна — доктор биологических наук, заведующая лабораторией биомедицинских исследований

690105, г. Владивосток, ул. Русская, 73-г.

Yulia K. Denisenko — Dr. Sci. (Biol.), Prof., Laboratory Head, Laboratory for Biomedical Research

690105, Vladivostok, Russkaya str., 73g.

karaman@inbox.ruКовалевскийД. А.KovalevskyD. A.

Ковалевский Даниил Андреевич — аспирант

690105, г. Владивосток, ул. Русская, 73-г.

Daniil A. Kovalevsky — Postgraduate Student

690105, Vladivostok, Russkaya str., 73g.

nauka@niivl.ruВладивостокский филиал ФГБНУ «Дальневосточный научный центр физиологии и патологии дыхания» — Научно-исследовательский институт медицинской климатологии и восстановительного леченияРоссияFar Eastern Scientific Centre for Physiology and Respiratory Pathology, Vladivostok Branch, Research Institute of Medical Climatology and Reconstructive TreatmentRussian Federation2020250320203021525Copyright © Кытикова О.Ю., Новгородцева Т.П., Денисенко Ю.К., Ковалевский Д.А., 20202020Кытикова О.Ю., Новгородцева Т.П., Денисенко Ю.К., Ковалевский Д.А.Kytikova O.Y., Novgorodtseva T.P., Denisenko Y.K., Kovalevsky D.A.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.gastro-j.ru/jour/article/view/446

Цель — представить данные литературы о метаболических и генетических механизмах нарушения синтеза жирных кислот (ЖК) в развитии и прогрессировании неалкогольной жировой болезни печени (НАЖБП).

Основное содержание

Основное содержание. НАЖБП — широко распространенное заболевание, прогрессирующее от стеатоза до неалкогольного стеатогепатита (НАСГ), которое увеличивает риск развития цирроза, печеночной недостаточности и гепатоцеллюлярной карциномы. Прогрессирование НАЖБП и развитие НАСГ тесно связаны с нарушениями липидного метаболизма, обусловленными не только недостаточным алиментарным поступлением жирных кислот, но и снижением эффективности процесса их эндогенной переработки. В регуляции метаболизма жирных кислот участвуют ферменты десатуразы (FADS1, FADS2) и элонгазы (ELOVL2 и ELOVL5) жирных кислот. Десатуразы кодируются генами десатураз жирных кислот FADS1 и FADS2. Полиморфизм в генах десатураз жирных кислот определяет эффективность эндогенной переработки ПНЖК. Нарушения активности FADS1 и FADS2 и их генов сопровождаются дерегуляцией метаболического пути, участвующего в биосинтезе жирных кислот, и приводят к повреждению клеточных мембран, в которых фосфолипиды являются основными компонентами. Прогрессирование НАЖБП связывают с мощной токсичностью липидов, высвобождаемых в паренхиме печени при потере целостности биомембран клеток.

Заключение

Заключение. Дальнейшее изучение генетических механизмов НАЖБП, вовлеченных в регуляцию метаболизма жирных кислот, позволит глубже понять патогенез данного многофакторного заболевания.

Aim

Aim. To present literature data on the metabolic and genetic mechanisms of impaired fatty acid (FA) synthesis in the development and progression of non-alcoholic fatty liver disease (NAFLD).

General findings

General findings. NAFLD is a widespread disease progressing from steatosis to non-alcoholic steatohepatitis (NASH), increasing the risk of cirrhosis, liver failure and hepatocellular carcinoma. Progression of NAFLD and the development of NASH are closely related to lipid metabolism disorders caused not only by insufficient alimentary intake of fatty acids, but also by a decrease in the efficiency of their endogenous processing. The regulation of fatty acid metabolism involves enzymes desaturase (FADS1, FADS2) and elongase (ELOVL2 and ELOVL5) fatty acids. Desaturases are encoded by the FADS1 and FADS2 genes for fatty acid desaturases. Polymorphisms in the genes of fatty acid desaturases determine the effectiveness of PUFA endogenous processing. Violations in the activity of FADS1 and FADS2 and their genes are accompanied by dysregulation of the metabolic pathway involved in the biosynthesis of fatty acids. This leads to the damage of cell membranes, whose main components are represented by phospholipids. The progression of NAFLD is associated with the powerful toxicity of lipids released in the liver parenchyma upon the loss of the cell biomembrane integrity.

Conclusions

Conclusions. Further research into the NAFLD genetic mechanisms regulating the metabolism of fatty acids appears to be promising for a deeper understanding of the pathogenesis of this multifactorial disease.

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The authors declare that there are no conflicts of interest present.