Federal Centre of Nutrition, Biotechnology, and Food Safety, Moscow, 109240, Russia.
Kulakov National Medical Research Center of Obstetrics, Gynecology, and Perinatology, Ministry of Health of the Russian Federation, Moscow, 117198, Russia.
Biochemistry (Mosc). 2019 Sep;84(9):1093-1106. doi: 10.1134/S0006297919090128.
Differential expression of 30,003 genes was studied in the liver of female Wistar rats fed with isocaloric diets with the excess of fat, fructose, or cholesterol, or their combinations for 62 days using the method of whole-transcriptome profiling on a microchip. Relative mRNA expression levels of the Asah2, Crot, Crtc2, Fmo3, GSTA2, LOC1009122026, LOC102551184, NpY, NqO1, Prom1, Retsat, RGD1305464, Tmem104, and Whsc1 genes were also determined by RT-qPCR. All the tested diets affected differently the key metabolic pathways (KEGGs). Significant changes in the expression of steroid metabolism gene were observed in the liver of animals fed with the tested diets (except the high-fat high fructose diet). Both high-fat and high-fructose diets caused a significant decrease in the expression of squalene synthase (FDFT1 gene) responsible for the initial stage of cholesterol synthesis. On the contrary, in animals fed with the high-cholesterol diet (0.5% cholesterol), expression of the FDFT1 gene did not differ from the control group; however, these animals were characterized by changes in the expression of glucose and glycogen synthesis genes, which could lead to the suppression of glycogen synthesis and gluconeogenesis. At the same time, this group demonstrated different liver tissue morphology in comparison with the animals fed with the high-fructose high-fat diet, manifested as the presence of lipid vacuoles of a smaller size in hepatocytes. The high-fructose and high-fructose high-fat diets affected the metabolic pathways associated with intracellular protein catabolism (endocytosis, phagocytosis, proteasomal degradation, protein processing in the endoplasmic reticulum), tight junctions and intercellular contacts, adhesion molecules, and intracellular RNA transport. Rats fed with the high-fructose high-fat or high-cholesterol diets demonstrated consistent changes in the expression of the Crot, Prom1, and RGD1305464 genes, which reflected a coordinated shift in the regulation of lipid and carbohydrate metabolisms.
采用微芯片全转录组谱法，研究了雌性 Wistar 大鼠在 62 天内分别用含过量脂肪、果糖或胆固醇或其组合的等热量饮食喂养后，肝脏中 30003 个基因的差异表达。还通过 RT-qPCR 测定了 Asah2、Crot、Crtc2、Fmo3、GSTA2、LOC1009122026、LOC102551184、NpY、NqO1、Prom1、Retsat、RGD1305464、Tmem104 和 Whsc1 基因的相对 mRNA 表达水平。所有测试的饮食都以不同的方式影响关键代谢途径（KEGGs）。在喂食测试饮食的动物肝脏中观察到类固醇代谢基因的表达发生了显著变化（除高脂肪高果糖饮食外）。高脂肪和高果糖饮食都导致胆固醇合成初始阶段的角鲨烯合酶（FDFT1 基因）的表达显著降低。相反，在喂食高胆固醇饮食（0.5%胆固醇）的动物中，FDFT1 基因的表达与对照组没有差异；然而，这些动物的特征是葡萄糖和糖原合成基因的表达发生变化，这可能导致糖原合成和糖异生受到抑制。同时，与喂食高脂肪高果糖饮食的动物相比，该组的肝脏组织形态发生了不同的变化，表现为肝细胞中脂质空泡的体积较小。高果糖和高脂肪高果糖饮食影响与细胞内蛋白质分解代谢（内吞作用、吞噬作用、蛋白酶体降解、内质网中蛋白质加工）、紧密连接和细胞间接触、黏附分子和细胞内 RNA 运输相关的代谢途径。喂食高脂肪高果糖或高胆固醇饮食的大鼠表现出 Crot、Prom1 和 RGD1305464 基因表达的一致变化，这反映了脂质和碳水化合物代谢调节的协调变化。
