The aim of review

gastro-j

Российский журнал гастроэнтерологии, гепатологии, колопроктологии

Russian Journal of Gastroenterology, Hepatology, Coloproctology

1382-43762658-6673

«Gastro» LLC

gastro-j-1261

Research Article

ГЕПАТОЛОГИЯ

HEPATOLOGY

Патогенетическое значение липидов при неалкогольной жировой болезни печени

Pathogenic role of lipids in non-alcoholic fatty liver disease

Шульпекова

Ю. О.

Shulpekova

Yu. O.

ГБОУ ВПО «Первый Московский государственный медицинский университет им. И.М. Сеченова» РосздраваRussian Federation

2012

10022012

2214556

2012

Шульпекова Ю.О.

Shulpekova Y.O.

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/1261

Цель обзора. Рассмотреть основные представления о повреждающей роли липидов в патогенезе неалкогольной жировой болезни печени (НАЖБП).Основные положения. По современным представлениям, центральную роль в повреждении клеток печени при НАЖБП играет стресс эндоплазматического ретикулума, который сопровождается дисфункцией белков – шаперонов. Последующие биохимические изменения ведут к нарушению клеточного дыхания, нарушению целостности митохондрий, повышают вероятность гибели гепатоцита. Непосредственным толчком для развития стресса эндоплазматического ретикулума служит избыточное накопление свободных жирных кислот, а индуцируемые ими события в клетке получили название«липотоксического стресса», «липоапоптоза».Максимальным повреждающим потенциалом обладают насыщенные жирные кислоты – пальмитиновая и стеариновая, что, возможно, объясняется их более медленным включением в состав эфиров. В патогенезе НАЖБП важную роль играют также другие повреждающие факторы, например окислительный стресс, поэтому сегодня правомерно существование теории «множественных параллельных толчков».Защитным действием могут обладать ненасыщенные жирные кислоты, эссенциальные фосфолипиды, антиоксиданты, силимарин, гиполипидемические средства, глитазоны. Изучается возможность лечебного применения ингибиторов каспаз, катепсина В, JNK-киназы, «химических шаперонов».Заключение. Липоапоптоз рассматривается как кардинальный признак НАЖБП, а свободные жирные кислоты – как активаторы программированной гибели гепатоцитов. Дальнейшее изучение молекулярных событий при липотоксическом стрессе, возможно, откроет новую страницу в лечении жировой болезни печени.

The aim of review

The aim of review. To discuss main concepts on the damaging role of lipids in non-alcoholic fatty liver diseases (NAFLD) pathogenesis.

Original points

Original points. According to modern concepts, at NAFLD stress of endoplasmic reticulum plays the central role in damage of liver cells which is accompanied by dysfunction of chaperone proteins. The subsequent biochemical changes cause disorders of cellular respiration, disorder of mitochondrial integrity, increase probability of hepatocyte death. Excessive accumulation of free fatty acids acts as direct impulse for development of endoplasmic reticulum stress, and resulting events inside a cell are named «lipotoxic stress» or «lipoapoptosis». Saturated fatty acids – palmitic and stearinic have maximal damaging potential, that, probably, is related to slower incorporation of esters. In NAFLD pathogenesis other damaging factors, e.g. oxidative stress play important role, therefore the theory of «multiple collateral impulses» is justified today. Unsaturated fatty acids, essential phospholipids, antioxidants, silymarinum, hypolipidemic agents, glitazones can have protective action. Potential of medical application of caspase inhibitors, cathepsine B, JNKkinase and «chemical chaperones» is under investigation.

Conclusion

Conclusion. Lipoapoptosis is considered as cardinal marker of NAFLD, and free fatty acids – as activators of the programmed death of hepatocytes. The further studying molecular events at lipotoxic stress will, probably, open new era in the treatment of fatty liver disease.

насыщенные и ненасыщенные жирные кислотылипотоксическийокислительный стресснеалкогольная жировая болезнь печенипатогенезлечение

saturated and unsaturated fatty acidslipotoxicoxidative stressnon-alcoholic fatty liver diseasepathogenesistreatment

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