Effects of diet and genetic background on sterol regulatory element-binding protein-1c, stearoyl-CoA desaturase 1, and the development of the metabolic syndrome
Effects of diet and genetic background on sterol regulatory element-binding protein-1c, stearoyl-CoA desaturase 1, and the development of the metabolic syndrome
复制标题
DOI：
10.2337/diabetes.54.5.1314
复制
发表时间：
2005-05-01
期刊：
影响因子：
7.7
通讯作者：
Kahn, CR
中科院分区：
文献类型：
--
作者：
Biddinger, SB;Almind, K;Kahn, CR
环境因素和遗传因素在代谢综合征的发生发展中起重要作用。为了阐明这些因子在正常条件下如何相互作用，将C57 B1/6（B6）和129 S6/SvEvTac（129）小鼠置于低脂或高脂饮食中。在18周内，129菌株发展出代谢综合征的特征，特别是肥胖，高胰岛素血症和葡萄糖耐受不良，仅在高脂肪饮食中;另一方面，B6菌株在两种饮食中都发展出这些特征。两种品系的高脂喂养导致血清甘油三酯降低、肝脂肪变性和高胆固醇血症;然而，B6小鼠发生了更严重的脂肪变性和LDL胆固醇的更大增加。B6背景和高脂喂养都增加了固醇调节元件结合蛋白-1c（SREBP-1c）及其下游靶点，该蛋白是脂肪生成基因转录的关键调节因子。硬脂酰辅酶A去饱和酶1（SCD 1），一种调节单不饱和脂肪酸（MUFA）合成的酶，也增加了mRNA和酶活性水平的高脂肪喂养和B6背景。此外，脂质分析显示B6和高脂肪喂养小鼠的肝脏甘油三酯和MUFA增加。因此，膳食脂肪和遗传背景通过SREBP-1c和SCD 1影响肝脏脂质代谢，促进代谢综合征的发展。
Both environmental and genetic factors play important roles in the development of the metabolic syndrome. To elucidate how these factors interact under normal conditions, C57B1/6 (B6) and 129S6/SvEvTac (129) mice were placed on a low-fat or high-fat diet. Over 18 weeks, the 129 strain developed features of the metabolic syndrome, notably obesity, hyperinsulinemia, and glucose intolerance only on the high-fat diet; the B6 strain on the other hand developed these features on both diets. High-fat feeding of both strains led to decreased serum triglycerides, hepatic steatosis, and hypercholesterolemia; however, B6 mice developed worse steatosis and a larger increase in LDL cholesterol. Both B6 background and high-fat feeding increased sterol regulatory element-binding protein-1c (SREBP-1c), a key regulator of lipogenic gene transcription, and its downstream targets. Stearoyl-CoA desaturase 1 (SCD1), an enzyme that regulates monounsaturated fatty acid (MUFA) synthesis, was also increased at the mRNA and enzyme activity levels by both high-fat feeding and B6 background. Furthermore, lipid analysis revealed increased hepatic triglycerides and MUFAs in B6 and high-fat-fed mice. Thus, dietary fat and genetic background act through SREBP-1c and SCD1 to affect hepatic lipid metabolism contributing to the development of the metabolic syndrome.