Engstler Anna Janina, Frahnow Turid, Kruse Michael, Pfeiffer Andreas Friedrich Hermann, Bergheim Ina
Institute of Nutrition,SD Model Systems of Molecular Nutrition,Friedrich-Schiller University of Jena,Jena,Germany.
Department of Clinical Nutrition (KLE),German Institute of Human Nutrition Potsdam-Rehbrücke (DIfE),Nuthetal,Germany.
Twin Res Hum Genet. 2017 Aug;20(4):338-348. doi: 10.1017/thg.2017.36. Epub 2017 Jun 21.
In different pathophysiological conditions plasminogen activator inhibitor-1 (PAI-1) plasma concentrations are elevated. As dietary patterns are considered to influence PAI-1 concentration, we aimed to determine active PAI-1 plasma concentrations and mRNA expression in adipose tissue before and after consumption of a high-fat diet (HFD) and the impact of additive genetic effects herein in humans. For 6 weeks, 46 healthy, non-obese pairs of twins (aged 18-70) received a normal nutritionally balanced diet (ND) followed by an isocaloric HFD for 6 weeks. Active PAI-1 plasma levels and PAI-1 mRNA expression in subcutaneous adipose tissue were assessed after the ND and after 1 and 6 weeks of HFD. Active PAI-1 plasma concentrations and PAI-1 mRNA expression in adipose tissue were significantly increased after both 1 and 6 weeks of HFD when compared to concentrations determined after ND (p < .05), with increases of active PAI-1 being independent of gender, age, or changes of BMI and intrahepatic fat content, respectively. However, analysis of covariance suggests that serum insulin concentration significantly affected the increase of active PAI-1 plasma concentrations. Furthermore, the increase of active PAI-1 plasma concentrations after 6 weeks of HFD was highly heritable (47%). In contrast, changes in PAI-1 mRNA expression in fatty tissue in response to HFD showed no heritability and were independent of all tested covariates. In summary, our data suggest that even an isocaloric exchange of macronutrients - for example, a switch to a fat-rich diet - affects PAI-1 concentrations in humans and that this is highly heritable.
在不同的病理生理条件下，血浆纤溶酶原激活物抑制剂-1（PAI-1）浓度会升高。由于饮食模式被认为会影响PAI-1浓度，我们旨在确定高脂饮食（HFD）前后人体血浆中活性PAI-1的浓度以及脂肪组织中PAI-1的mRNA表达，以及加性基因效应在此过程中的影响。46对健康、非肥胖的双胞胎（年龄在18 - 70岁之间）先接受了6周营养均衡的正常饮食（ND），随后接受了6周等热量的HFD。在ND结束时以及HFD开始1周和6周后，评估皮下脂肪组织中活性PAI-1的血浆水平和PAI-1的mRNA表达。与ND后测定的浓度相比，HFD 1周和6周后，脂肪组织中活性PAI-1的血浆浓度和PAI-1的mRNA表达均显著增加（p < 0.05），活性PAI-1的增加分别与性别、年龄、BMI和肝内脂肪含量的变化无关。然而，协方差分析表明，血清胰岛素浓度显著影响活性PAI-1血浆浓度的增加。此外，HFD 6周后活性PAI-1血浆浓度的增加具有高度遗传性（47%）。相比之下，脂肪组织中PAI-1的mRNA表达对HFD的反应变化没有遗传性，且与所有测试的协变量无关。总之，我们的数据表明，即使是宏量营养素的等热量交换——例如，换成富含脂肪的饮食——也会影响人体中的PAI-1浓度，而且这种影响具有高度遗传性。
