Мутация yellow в локусе agouti устраняет возрастное повышение экспрессии генов белков, регулирующих окисление жирных кислот в мышцах у мышей

Мутация yellow в локусе agouti (Ay мутация), снижающая активность меланокортиновых рецепторов, с возрастом вызывает гиперфагию, ожирение и диабет второго типа у мышей (Ay мыши). Неизвестно, будут ли у Ay мышей изменения в отдельных звеньях метаболической системы (белый и бурый жир и мышцы) проявляться еще до развития ожирения. Цель работы – измерить у Ay мышей относительную экспрессию генов ключевых белков, регулирующих углеводно-жировой обмен в белом и буром жире и скелетной мускулатуре на этапах развития, предшествующих формированию ожирения. Исследовали мышей линии C57Bl/6J, несущих доминантную аутосомную мутацию Ay (Ay /a мыши), и мышей стандартного генотипа данной линии (a/a мыши, контроль) в трех возрастных группах: 10, 15 и 30 нед. Методом ПЦР в реальном времени измеряли относительный уровень мРНК генов в мышцах: uncoupling protein 3 (Ucp3) и carnitine palmitoyl transferase 1b (Cpt1b) (окисление СЖК), solute carrier family 2 (facilitated glucose transporter), member 4 (Slc2a4) (захват глюкозы); в белом жире: lipoprotein lipase (Lpl) (депонирование триглицеридов), hormone-sensitive lipase (Lipe) (мобилизация жиров) и Slc2a4 (захват глюкозы); в буром жире: uncoupling protein 1 (Ucp1) (расход энергии). В молодом возрасте (10 нед) у Ay мышей в мышцах была снижена экспрессия Cpt1b, в 15 нед у них отсутствовал транзиторный пик транскрипции Cpt1b, Ucp3 в мышцах, а также Lipe и Slc2a4 в белом жире, который отмечался у a/a мышей. Снижение транскрипционной активности исследованных генов в скелетных мышцах и белом жире может инициировать развитие меланокортинового ожирения у Ay мышей.

мыши линии C57Bl/6J, ПЦР в реальном времени, меланокортиновое ожирение, углеводно-жировой обмен

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