胆固醇7α羟化酶
内科学
内分泌学
胆固醇
断奶
后代
分解代谢
宫内生长受限
医学
生物
胎儿
怀孕
新陈代谢
遗传学
作者
Erin K. Zinkhan,Baifeng Yu,Amnon Schlegel
标识
DOI:10.3389/fphys.2018.00645
摘要
Intrauterine growth restriction (IUGR) and consumption of a high saturated fat diet (HFD) increase the risk of hypercholesterolemia, a leading cause of morbidity and mortality. The mechanism through which the cumulative impact of IUGR and in utero exposure to a maternal HFD increase cholesterol levels remains unknown. Cholesterol 7α hydroxylase (Cyp7a1) initiates catabolism of cholesterol to bile acids for elimination from the body, and is regulated by microRNA-122 (miR-122). We hypothesized that IUGR rats exposed to a maternal HFD would have increased cholesterol and decreased Cyp7a1 protein levels in juvenile rats, findings which would be normalized by administration of a miR-122 inhibitor. To test our hypothesis we used a rat model of surgically induced IUGR and fed the dams a regular diet or a HFD from prior to conception through lactation. At the time of weaning, IUGR female rats exposed to a maternal HFD had increased hepatic cholesterol, decreased hepatic Cyp7a1 protein and hepatic bile acids, and increased hepatic miR-122 compared to non-IUGR rats exposed to the same HFD. In vivo inhibition of miR-122 increased hepatic Cyp7a1 protein and decreased hepatic cholesterol. Our findings suggest that IUGR combined with a maternal HFD decreased cholesterol catabolism to bile acids, in part, via miR-122 inhibition of Cyp7a1.
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