Graduate School of Regional Innovation Studies, Mie University, 1577 Kurimamachiya-cho, Tsu 514-8507, Japan.
Nutr Metab (Lond). 2012 Sep 21;9(1):87. doi: 10.1186/1743-7075-9-87.
It is difficult to study the mechanisms of the metabolic syndrome in humans due to the heterogeneous genetic background and lifestyle. The present study investigated changes in the gene and protein profiles in an animal model of the metabolic syndrome to identify the molecular targets associated with the pathogenesis and progression of obesity related to the metabolic syndrome.
We extracted mRNAs and proteins from the liver tissues of 6- and 25-week-old spontaneously hypertensive/NIH -corpulent rat SHR/NDmcr-cp (CP), SHR/Lean (Lean) and Wistar Kyoto rats (WKY) and performed microarray analysis and two-dimensional difference in gel electrophoresis (2D-DIGE) linked to a matrix-assisted laser desorption ionization time-of-flight tandem mass spectrometry (MALDI-TOF/TOF MS).
The microarray analysis identified 25 significantly up-regulated genes (P < 0.01; log10 > 1) and 31 significantly down-regulated genes (P < 0.01; log10 < -1) in 6- and 25-week-old CP compared with WKY and Lean. Several of these genes are known to be involved in important biological processes such as electron transporter activity, electron transport, lipid metabolism, ion transport, transferase, and ion channel activity. MALDI-TOF/TOF MS identified 31 proteins with ±1.2 fold change (P < 0.05) in 6- and 25-week-old CP, compared with age-matched WKY and Lean. The up-regulated proteins are involved in metabolic processes, biological regulation, catalytic activity, and binding, while the down-regulated proteins are involved in endoplasmic reticulum stress-related unfolded protein response.
Genes with significant changes in their expression in transcriptomic analysis matched very few of the proteins identified in proteomics analysis. However, annotated functional classifications might provide an important reference resource to understand the pathogenesis of obesity associated with the metabolic syndrome.
由于遗传背景和生活方式的异质性，很难在人类中研究代谢综合征的机制。本研究通过动物模型研究代谢综合征中基因和蛋白质谱的变化，以鉴定与肥胖相关的代谢综合征发病机制和进展相关的分子靶标。
我们从 6 周和 25 周龄自发性高血压/ NIH -肥胖大鼠 SHR/NDmcr-cp (CP)、SHR/Lean (Lean)和 Wistar Kyoto 大鼠 (WKY)的肝组织中提取 mRNA 和蛋白质，进行微阵列分析和二维差异凝胶电泳 (2D-DIGE) 与基质辅助激光解吸电离飞行时间串联质谱 (MALDI-TOF/TOF MS) 相连。
微阵列分析鉴定出 25 个在 6 周和 25 周龄 CP 中与 WKY 和 Lean 相比显著上调的基因 (P < 0.01；log10 > 1) 和 31 个显著下调的基因 (P < 0.01；log10 < -1)。其中一些基因已知参与重要的生物学过程，如电子转运体活性、电子传递、脂质代谢、离子转运、转移酶和离子通道活性。MALDI-TOF/TOF MS 鉴定出 31 种蛋白质，在 6 周和 25 周龄 CP 中与年龄匹配的 WKY 和 Lean 相比，其变化倍数为±1.2 (P < 0.05)。上调的蛋白质参与代谢过程、生物调节、催化活性和结合，而下调的蛋白质则参与内质网应激相关的未折叠蛋白反应。
在转录组分析中表达有显著变化的基因与蛋白质组学分析中鉴定出的蛋白质很少匹配。然而，注释的功能分类可能为理解与肥胖相关的代谢综合征的发病机制提供重要的参考资源。
