Ferenc K, Pietrzak P, Wierzbicka M, Matyba P, Grzesiuk E, Gajewski Z, Zabielski R
Veterinary Research Centre and Center for Biomedical Research, Department of Large Animal Diseases with Clinic, Faculty of Veterinary Medicine, Warsaw University of Life Sciences, Warsaw, Poland.
Department of Molecular Biology, Institute of Biochemistry and Biophysics, Polish Academy of Sciences, Warsaw, Poland.
J Physiol Pharmacol. 2018 Apr;69(2). doi: 10.26402/jpp.2018.2.06. Epub 2018 Jun 13.
Intrauterine growth retardation (IUGR) leads to increased predisposition to metabolic syndrome in adult life but the mechanisms remain obscure. Considering a significant number of functional similarities, IUGR piglets appear to be a good model to study the development of this syndrome in humans. The aim of the present study was to investigate the ultrastructure and proteomic profile of the liver in IUGR pig neonates to discover early markers of predisposition to obesity and insulin resistance. In our study intestine and liver tissue samples were investigated in 7 day old IUGR and normal body weight (NBW) littermate piglets using histometry, mass spectrometry, in-tissue cytometry analysis and confocal microscopy. Compared to NBW, the liver in IUGR neonates was characterized by a significantly enhanced ratio of Kupffer cells to hepatocytes and insulin receptor abundance as well as higher percentages of cells expressing receptors for adipokines (resistin and adiponectin), increased expression of TNF-α (as marker of inflammation), and increased expression of insulin receptor and uncoupling protein 3 (UCP3). Moreover, NBW and IUGR differed in proteomic profile, including protein metabolism (proteasomes, cathepsin D, phermitin, phosphoglucomutase), carbohydrate metabolism (hexokinase 1, phosphoglucokinase, galactokinase, aldolase B, glucose-6-phosphate isomerase), oxidative stress and chromatin organization and DNA uptake (histones, lamin a/c). Reduction of hepatocyte numbers concomitant with significant modifications of expression of key hormones and enzymes for protein and carbohydrate metabolism in IUGR neonates may predispose to insulin resistance and obesity in adult life.
宫内生长受限（IUGR）会导致成年后代谢综合征的易感性增加，但其机制仍不清楚。鉴于大量的功能相似性，IUGR仔猪似乎是研究人类该综合征发展的良好模型。本研究的目的是调查IUGR新生仔猪肝脏的超微结构和蛋白质组学特征，以发现肥胖和胰岛素抵抗易感性的早期标志物。在我们的研究中，使用组织计量学、质谱分析、组织内细胞计数分析和共聚焦显微镜，对7日龄IUGR和正常体重（NBW）同窝仔猪的肠和肝组织样本进行了研究。与NBW仔猪相比，IUGR新生仔猪的肝脏具有以下特征：库普弗细胞与肝细胞的比例显著增加，胰岛素受体丰度增加，以及表达脂肪因子（抵抗素和脂联素）受体的细胞百分比更高，TNF-α表达增加（作为炎症标志物），胰岛素受体和解偶联蛋白3（UCP3）表达增加。此外，NBW和IUGR在蛋白质组学特征上存在差异，包括蛋白质代谢（蛋白酶体、组织蛋白酶D、phermitin、磷酸葡萄糖变位酶）、碳水化合物代谢（己糖激酶1、磷酸葡萄糖激酶、半乳糖激酶、醛缩酶B、葡萄糖-6-磷酸异构酶）、氧化应激以及染色质组织和DNA摄取（组蛋白、核纤层蛋白a/c）。IUGR新生仔猪肝细胞数量减少，同时蛋白质和碳水化合物代谢的关键激素和酶的表达发生显著改变，这可能会导致成年后胰岛素抵抗和肥胖。
