Cardiovascular Nutrition Laboratory, Jean Mayer US Department of Agriculture, Human Nutrition Research Center on Aging at Tufts University, Boston, MA 02111, USA.
Metabolism. 2010 Oct;59(10):1491-501. doi: 10.1016/j.metabol.2010.01.014. Epub 2010 Mar 2.
Cholesterol status and dietary fat alter several metabolic pathways reflected in lipoprotein profiles. To assess plasma lipoprotein response and mechanisms by which cholesterol and dietary fat type regulate expression of genes involved in lipoprotein metabolism, we developed an experimental model system using F1B hamsters fed diets (12 weeks) enriched in 10% (wt/wt) coconut, olive, or safflower oil with either high cholesterol (0.1%; cholesterol supplemented) or low cholesterol coupled with cholesterol-lowering drugs 10 days before killing (0.01% cholesterol, 0.15% lovastatin, 2% cholestyramine; cholesterol depleted). Irrespective of dietary fat, cholesterol depletion, relative to supplementation, resulted in lower plasma non-high-density lipoprotein (non-HDL) and HDL cholesterol, and triglyceride concentrations (all Ps < .05). In the liver, these differences were associated with higher sterol regulatory element binding protein-2, low-density lipoprotein receptor, 3-hydroxy-3-methylglutaryl coenzyme A reductase, and 7α-hydroxylase messenger RNA (mRNA) levels; higher scavenger receptor B1 and apolipoprotein A-I mRNA and protein levels; lower apolipoprotein E protein levels; and in intestine, modestly lower sterol transporters adenosine triphosphate-binding cassette (ABC) A1, ABCG5, and ABCG8 mRNA levels. Irrespective of cholesterol status, coconut oil, relative to olive and safflower oils, resulted in higher non-HDL cholesterol and triglyceride concentrations (both Ps < .05) and modestly higher sterol regulatory element binding protein-2 mRNA levels. These data suggest that, in F1B hamsters, differences in plasma lipoprotein profiles in response to cholesterol depletion are associated with changes in the expression of genes involved in cholesterol metabolism, whereas the effect of dietary fat type on gene expression was modest, which limits the usefulness of the experimental animal model.
胆固醇水平和膳食脂肪会改变脂蛋白谱中反映的几种代谢途径。为了评估血浆脂蛋白的反应以及胆固醇和膳食脂肪类型调节参与脂蛋白代谢的基因表达的机制，我们开发了一种实验模型系统，使用 F1B 仓鼠喂食富含 10%（wt/wt）椰子油、橄榄油或红花油的饮食（12 周），其中含有高胆固醇（0.1%；补充胆固醇）或低胆固醇并在处死前 10 天添加降胆固醇药物（0.01%胆固醇、0.15%洛伐他汀、2%考来烯胺；胆固醇耗尽）。无论膳食脂肪如何，与补充相比，胆固醇耗尽导致非高密度脂蛋白（非 HDL）和 HDL 胆固醇以及甘油三酯浓度降低（均 P<.05）。在肝脏中，这些差异与固醇调节元件结合蛋白-2、低密度脂蛋白受体、3-羟-3-甲基戊二酰辅酶 A 还原酶和 7α-羟化酶信使 RNA（mRNA）水平升高； scavenger 受体 B1 和载脂蛋白 A-I mRNA 和蛋白水平升高；载脂蛋白 E 蛋白水平降低；在肠道中，固醇转运体三磷酸腺苷结合盒（ABC）A1、ABCG5 和 ABCG8 mRNA 水平适度降低有关。无论胆固醇状态如何，与橄榄油和红花油相比，椰子油导致非 HDL 胆固醇和甘油三酯浓度升高（均 P<.05），固醇调节元件结合蛋白-2 mRNA 水平略有升高。这些数据表明，在 F1B 仓鼠中，胆固醇耗竭后血浆脂蛋白谱的差异与胆固醇代谢相关基因表达的变化有关，而膳食脂肪类型对基因表达的影响较小，这限制了实验动物模型的实用性。
