Inhibiting Cholesterol Absorption During Lactation Programs Future Intestinal Absorption of Cholesterol in Adult Mice
Inhibiting Cholesterol Absorption During Lactation Programs Future Intestinal Absorption of Cholesterol in Adult Mice
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DOI：
10.1053/j.gastro.2017.04.019
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发表时间：
2017-08-01
期刊：
影响因子：
29.4
通讯作者：
Tietge, Uwe J. F.
中科院分区：
文献类型：
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作者：
Dimova, Lidiya G.;de Boer, Jan Freark;Tietge, Uwe J. F.
在线虫中，肠道感知并整合早期生命的饮食线索，这些线索导致终身表观遗传适应所感知的营养环境-目前尚不清楚这一过程是否发生在哺乳动物身上。我们的目标是建立母乳中饮食胆固醇供应减少的小鼠模型，并调查生命早期母乳胆固醇供应减少对成年小鼠胆固醇代谢的影响。我们在喂给新生小鼠的牛奶中添加依折替米布(从出生到断奶3周)，阻止它们在肠道中吸收胆固醇，依折替米布分泌到牛奶中。Ezetimibe与肠道胆固醇吸收转运蛋白NPC1L1相互作用，阻止胆固醇进入肠细胞。这些子代在24周龄时的特征表明，胆固醇吸收减少了27%(P
In nematodes, the intestine senses and integrates early life dietary cues that lead to lifelong epigenetic adaptations to a perceived nutritional environment-it is not clear whether this process occurs in mammals. We aimed to establish a mouse model of reduced dietary cholesterol availability from maternal milk and investigate the consequences of decreased milk cholesterol availability, early in life, on the metabolism of cholesterol in adult mice. We blocked intestinal absorption of cholesterol in milk fed to newborn mice by supplementing the food of dams (for 3 weeks between birth and weaning) with ezetimibe, which is secreted into milk. Ezetimibe interacts with the intestinal cholesterol absorption transporter NPC1l1 to block cholesterol uptake into enterocytes. Characterization of these offspring at 24 weeks of age showed a 27% decrease in cholesterol absorption (P