Метаболические и генетические детерминанты нарушения липидного обмена при неалкогольной жировой болезни печени

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

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