Abstract：
Several corresponding regions of human and mammalian genomes have been shown to affect sensitivity to the manifestation of metabolic syndrome via nutrigenetic interactions. In this study, we assessed the effect of sucrose administration in a newly established congenic strain BN.SHR20, in which a limited segment of rat chromosome 20 from a metabolic syndrome model, spontaneously hypertensive rat (SHR), was introgressed into Brown Norway (BN) genomic background. We mapped the extent of the differential segment and compared the genomic sequences of BN vs. SHR within the segment in silico. The differential segment of SHR origin in BN.SHR20 spans about 9 Mb of the telomeric portion of the short arm of chromosome 20. We identified non-synonymous mutations e.g., in ApoM, Notch4, Slc39a7, Smim29 genes and other variations in or near genes associated with metabolic syndrome in human genome-wide association studies. Male rats of BN and BN.SHR20 strains were fed a standard diet for 18 weeks (control groups) or 16 weeks of standard diet followed by 14 days of high-sucrose diet (HSD). We assessed the morphometric and metabolic profiles of all groups. Adiposity significantly increased only in BN.SHR20 after HSD. Fasting glycemia and the glucose levels during the oral glucose tolerance test were higher in BN.SHR20 than in BN groups, while insulin levels were comparable. The fasting levels of triacylglycerols were the highest in sucrose-fed BN.SHR20, both compared to the sucrose-fed BN and the control BN.SHR20. The non-esterified fatty acids and total cholesterol concentrations were higher in BN.SHR20 compared to their respective BN groups, and the HSD elicited an increase in non-esterified fatty acids only in BN.SHR20. In a new genetically defined model, we have isolated a limited genomic region involved in nutrigenetic sensitization to sucrose-induced metabolic disturbances.
摘要：
已显示人类和哺乳动物基因组的几个相应区域通过营养遗传相互作用影响对代谢综合征表现的敏感性。在这项研究中,我们评估了蔗糖在新建立的同基因菌株BN中的作用。SHR20，其中来自代谢综合征模型的大鼠染色体20的有限片段，自发性高血压大鼠（SHR），渗入布朗挪威（BN）基因组背景。我们绘制了差异片段的范围，并比较了BN与BN的基因组序列SHR在silico段内。BN中SHR起源的微分段。SHR20跨越20号染色体短臂端粒部分的约9Mb。我们鉴定了非同义突变，例如，在ApoM,Notch4、Slc39a7、Smim29基因和其他与人类全基因组关联研究中代谢综合征相关基因的变异。BN和BN的雄性大鼠。将SHR20菌株饲喂标准饮食18周（对照组）或16周的标准饮食，然后是14天的高蔗糖饮食（HSD）。我们评估了所有组的形态测量和代谢谱。仅在BN中，脂肪显着增加。HSD后的SHR20。BN中空腹血糖和口服葡萄糖耐量试验期间的葡萄糖水平较高。SHR20比BN组，而胰岛素水平相当。在蔗糖喂养的BN中，三酰基甘油的空腹水平最高。SHR20均与蔗糖进料的BN和对照BN相比。SHR20.BN中未酯化的脂肪酸和总胆固醇浓度较高。SHR20与各自的BN组相比，HSD仅在BN中引起非酯化脂肪酸的增加。SHR20.在一个新的基因定义模型中，我们已经分离了一个有限的基因组区域，该区域涉及对蔗糖诱导的代谢紊乱的营养遗传敏感性。
