Mutungi Gisella, Torres-Gonzalez Moises, McGrane Mary M, Volek Jeff S, Fernandez Maria Luz
Department of Nutritional Sciences, University of Connecticut, Storrs, CT, 06269 USA.
Lipids Health Dis. 2007 Nov 28;6:34. doi: 10.1186/1476-511X-6-34.
The liver is responsible for controlling cholesterol homeostasis in the body. HMG-CoA reductase and the LDL receptor (LDL-r) are involved in this regulation and are also ubiquitously expressed in all major tissues. We have previously shown in guinea pigs that there is a correlation in gene expression of HMG-CoA reductase and the LDL-r between liver and mononuclear cells. The present study evaluated human mononuclear cells as a surrogate for hepatic expression of these genes. The purpose was to evaluate the effect of dietary carbohydrate restriction with low and high cholesterol content on HMG-CoA reductase and LDL-r mRNA expression in mononuclear cells. All subjects were counseled to consume a carbohydrate restricted diet with 10-15% energy from carbohydrate, 30-35% energy from protein and 55-60% energy from fat. Subjects were randomly assigned to either EGG (640 mg/d additional dietary cholesterol) or SUB groups [equivalent amount of egg substitute (0 dietary cholesterol contributions) per day] for 12 weeks. At the end of the intervention, there were no changes in plasma total or LDL cholesterol (LDL-C) compared to baseline (P > 0.10) or differences in plasma total or LDL-C between groups. The mRNA abundance for HMG-CoA reductase and LDL-r were measured in mononuclear cells using real time PCR. The EGG group showed a significant decrease in HMG-CoA reductase mRNA (1.98 +/- 1.26 to 1.32 +/- 0.92 arbitrary units P < 0.05) while an increase was observed for the SUB group (1.13 +/- 0.52 to 1.69 +/- 1.61 arbitrary units P < 0.05). Additionally, the LDL-r mRNA abundance was decreased in the EGG group (1.72 +/- 0.69 to 1.24 +/- 0.55 arbitrary units P < 0.05) and significantly increased in the SUB group (1.00 +/- 0.60 to 1.67 +/- 1.94 arbitrary units P < 0.05). The findings indicate that dietary cholesterol during a weight loss intervention alters the expression of genes regulating cholesterol homeostasis.
肝脏负责控制体内胆固醇的稳态。3-羟基-3-甲基戊二酰辅酶A还原酶（HMG-CoA还原酶）和低密度脂蛋白受体（LDL-r）参与这一调节过程，并且在所有主要组织中均有广泛表达。我们之前在豚鼠中发现，肝脏和单核细胞中HMG-CoA还原酶与LDL-r的基因表达存在相关性。本研究将人类单核细胞作为这些基因肝脏表达的替代物进行评估。目的是评估低胆固醇和高胆固醇含量的碳水化合物限制饮食对单核细胞中HMG-CoA还原酶和LDL-r mRNA表达的影响。所有受试者均被建议食用碳水化合物限制饮食，其中碳水化合物提供10%-15%的能量，蛋白质提供30%-35%的能量，脂肪提供55%-60%的能量。受试者被随机分为鸡蛋组（每天额外摄入640毫克膳食胆固醇）或替代组[每天等量的鸡蛋替代品（膳食胆固醇贡献为0）]，为期12周。干预结束时，与基线相比，血浆总胆固醇或低密度脂蛋白胆固醇（LDL-C）没有变化（P>0.10），两组之间的血浆总胆固醇或LDL-C也没有差异。使用实时PCR测定单核细胞中HMG-CoA还原酶和LDL-r的mRNA丰度。鸡蛋组中HMG-CoA还原酶mRNA显著降低（从1.98±1.26任意单位降至1.32±0.92任意单位，P<0.05），而替代组中则有所增加（从1.13±0.52任意单位增至1.69±1.61任意单位，P<0.05）。此外，鸡蛋组中LDL-r mRNA丰度降低（从1.72±0.69任意单位降至1.24±0.55任意单位，P<0.05），替代组中则显著增加（从1.00±0.60任意单位增至1.67±1.94任意单位，P<0.05）。研究结果表明，减肥干预期间的膳食胆固醇会改变调节胆固醇稳态的基因表达。
