Seda O, Kazdová L, Sedová L, Liska F, Krenová D, Kren V
Institute of Biology and Medical Genetics of the First Faculty of Medicine, Charles University in Prague, Albertov 4, 128 00 Prague 2, Czech Republic.
Prague Med Rep. 2006;107(2):251-60.
We have previously established a congenic strain SHR-Lx that carries a differential segment of rat chromosome 8 introgressed from a model of metabolic syndrome--the polydactylous rat strain--on the genomic background of spontaneously hypertensive rat (SHR). We compared the glucose tolerance and lipid profile of adult SHR and SHR-Lx males under conditions of standard diet and diets enriched in sucrose and cholesterol, respectively. While there was no evident difference between the SHR and SHR-Lx on standard diet, the one-week sucrose administration revealed the congenic strain sensitivity to carbohydrate-induced dyslipidemia conferred by the differential segment with only mild derangement of glucose tolerance. On the other hand, the high-cholesterol diet administration for three-weeks resulted in a contrasting pattern as the congenic strain displayed significantly lower concentrations of free fatty acids and improved glucose tolerance compared to SHR. After one-month washout period, the SHR-Lx showed higher insulin, triglyceride and cholesterol concentrations together with diminished insulin sensitivity of visceral adipose tissue. In summary, we have identified a genomic region syntenic to human chromosome 11q23, which determines complex nutrigenetic interactions under conditions of sucrose- and cholesterol-enriched diets.
我们之前建立了一个同源近交系SHR-Lx,它在自发性高血压大鼠(SHR)的基因组背景上,携带了一段从代谢综合征模型——多指大鼠品系——导入的大鼠8号染色体差异片段。我们分别比较了成年SHR和SHR-Lx雄性大鼠在标准饮食以及富含蔗糖和胆固醇的饮食条件下的葡萄糖耐量和血脂谱。在标准饮食条件下,SHR和SHR-Lx之间没有明显差异,但为期一周的蔗糖给药显示,同源近交系对由差异片段导致的碳水化合物诱导的血脂异常敏感,而葡萄糖耐量仅有轻微紊乱。另一方面,为期三周的高胆固醇饮食导致了一种相反的模式,因为与SHR相比,同源近交系的游离脂肪酸浓度显著降低,葡萄糖耐量得到改善。在为期一个月的洗脱期后,SHR-Lx的胰岛素、甘油三酯和胆固醇浓度升高,同时内脏脂肪组织的胰岛素敏感性降低。总之,我们确定了一个与人类11号染色体q23区域同源的基因组区域,该区域在富含蔗糖和胆固醇的饮食条件下决定了复杂的营养基因相互作用。