Huang Haiqiu, Xie Zhuohong, Yokoyama Wallace, Yu Liangli, Wang Thomas T Y
Diet, Genomics and Immunology Laboratory , USDA-ARS , Beltsville , MD 20705 , USA.
International Chemistry Testing , Milford , MA 01757 , USA.
J Nutr Sci. 2016 Mar 30;5:e16. doi: 10.1017/jns.2016.3. eCollection 2016.
Hypercholesterolaemia is a risk factor for CVD, which is a leading cause of death in industrialised societies. The biosynthetic pathways for cholesterol metabolism are well understood; however, the regulation of circulating cholesterol by diet is still not fully elucidated. The present study aimed to gain more comprehensive understanding of the relationship between circulating cholesterol levels and molecular effects in target tissues using the hamster model. Male golden Syrian hamsters were fed with chow or diets containing 36 % energy from fat with or without 1 % cholesteyramine (CA) as a modulator of circulating cholesterol levels for 35 d. It was revealed that the expression of lanosterol 14α-demethylase (CYP51) instead of 3-hydroxy-3-methyl-glutaryl (HMG)-CoA reductase mRNA expression was responsive to circulating cholesterol in hamsters fed hypercholesterolaemic diets. The high-fat diet increased circulating cholesterol and down-regulated CYP51, but not HMG-CoA reductase. The CA diet decreased cholesterol and increased CYP51 expression, but HMG-CoA reductase expression was not affected. The high-fat diet and CA diet altered the expression level of cholesterol, bile acids and lipid metabolism-associated genes (LDL receptor, cholesterol 7α-hydroxylase (CYP7A1), liver X receptor (LXR) α, and ATP-binding cassette subfamily G member 5/8 (ABCG5/8)) in the liver, which were significantly correlated with circulating cholesterol levels. Correlation analysis also showed that circulating cholesterol levels were regulated by LXR/retinoid X receptor and PPAR pathways in the liver. Using the hamster model, the present study provided additional molecular insights into the influence of circulating cholesterol on hepatic cholesterol metabolism pathways during hypercholesterolaemia.
高胆固醇血症是心血管疾病（CVD）的一个危险因素，而心血管疾病是工业化社会中主要的死亡原因。胆固醇代谢的生物合成途径已为人熟知；然而，饮食对循环胆固醇的调节作用仍未完全阐明。本研究旨在利用仓鼠模型更全面地了解循环胆固醇水平与靶组织分子效应之间的关系。雄性金黄叙利亚仓鼠分别喂食普通饲料或含有36%能量来自脂肪的饲料，其中部分饲料添加或不添加1%消胆胺（CA）作为循环胆固醇水平的调节剂，持续35天。结果显示，在喂食高胆固醇饮食的仓鼠中，羊毛甾醇14α-去甲基酶（CYP51）的表达而非3-羟基-3-甲基戊二酰（HMG）-辅酶A还原酶mRNA的表达对循环胆固醇有反应。高脂饮食增加了循环胆固醇并下调了CYP51，但未影响HMG-辅酶A还原酶。CA饮食降低了胆固醇并增加了CYP51的表达，但HMG-辅酶A还原酶的表达未受影响。高脂饮食和CA饮食改变了肝脏中胆固醇、胆汁酸和脂质代谢相关基因（低密度脂蛋白受体、胆固醇7α-羟化酶（CYP7A1）、肝脏X受体（LXR）α以及ATP结合盒转运体G亚家族成员5/8（ABCG5/8））的表达水平，这些基因与循环胆固醇水平显著相关。相关性分析还表明，肝脏中的LXR/视黄酸X受体和PPAR途径调节循环胆固醇水平。本研究利用仓鼠模型，为高胆固醇血症期间循环胆固醇对肝脏胆固醇代谢途径的影响提供了更多分子层面的见解。
