REGULATION OF HEPATIC 7-ALPHA-HYDROXYLASE EXPRESSION AND RESPONSE TO DIETARY-CHOLESTEROL IN THE RAT AND HAMSTER
REGULATION OF HEPATIC 7-ALPHA-HYDROXYLASE EXPRESSION AND RESPONSE TO DIETARY-CHOLESTEROL IN THE RAT AND HAMSTER
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DOI：
10.1074/jbc.270.10.5381
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发表时间：
1995-03-10
影响因子：
4.8
通讯作者：
SPADY, DK
中科院分区：
文献类型：
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作者：
HORTON, JD;CUTHBERT, JA;SPADY, DK
尽管膳食胆固醇会提高血浆总胆固醇和低密度脂蛋白(LDL)胆固醇浓度，但不同物种甚至同一物种的个体对特定胆固醇摄入量的反应存在巨大差异。通过将能够适应类固醇摄入量或摄入量的大幅波动而血浆低密度脂蛋白水平变化不大的大鼠与类固醇平衡变化强烈影响血浆低密度脂蛋白浓度的仓鼠进行比较，研究了导致对饮食胆固醇敏感性不同的机制。当喂食相同的无胆固醇饮食时，大鼠的肝脏7α-羟基酶活性是仓鼠的16倍。因此，大鼠的肝脏胆固醇合成率是仓鼠的20倍，在这两个物种中，肝脏胆固醇合成都受到了90%的抑制，这是对饮食中胆固醇负荷增加的反应。然而，这种适应机制在大鼠中的数量重要性要大得多，因为大鼠肝脏胆固醇合成的绝对降幅(2,110nmol/h/g)远远大于仓鼠(103nmol/h/g)。在大鼠中，底物(胆固醇)进一步诱导了高基础水平的7α-羟基酶的表达，使这些动物能够有效地将过量的饮食胆固醇转化为胆汁酸。相比之下，低基础水平的酶在仓鼠中的表达不是由饮食中的胆固醇诱导的。因此，低胆汁酸和胆固醇合成的基础速率，再加上胆固醇诱导的7α-羟基酶的缺乏，使得仓鼠对饮食胆固醇的降胆固醇效应比大鼠更敏感。
Although dietary cholesterol raises plasma total and low density lipoprotein (LDL) cholesterol concentrations, the response to a given intake of cholesterol varies enormously among different species and even among individuals of the same species. The mechanisms responsible for differing sensitivity to dietary cholesterol were examined by comparing the rat, which is able to adapt to large fluctuations in sterol intake or loss with little change in plasma LDL levels, with the hamster, where changes in sterol balance strongly influence plasma LDL concentrations. When fed the same cholesterol-free diet, hepatic 7 alpha-hydroxylase activity was 16-fold higher in the rat than in the hamster. As a consequence, rates of hepatic cholesterol synthesis were 20-fold higher in the rat than in the hamster, In both species, hepatic cholesterol synthesis was suppressed >90% in response to increasing loads of dietary cholesterol. However, the quantitative importance of this adaptive mechanism was much greater in the rat since the absolute reduction in hepatic cholesterol synthesis in the rat (2,110 nmol/h/g) was much larger than in the hamster (103 nmol/h/g). In the rat, the high basal level of 7 alpha-hydroxylase expression was further induced by substrate (cholesterol) allowing these animals to convert excess dietary cholesterol to bile acids efficiently. In contrast, the low basal level of enzyme expression in the hamster was not induced by dietary cholesterol. Thus, the low basal rates of bile acid and cholesterol synthesis coupled with a lack of 7 alpha-hydroxylase induction by cholesterol render the hamster much more sensitive than the rat to the cholesterolemic effects of dietary cholesterol.