Laboratory Animal Center, Shanxi Key Laboratory of Experimental Animal Science and Animal Model of Human Disease, Shanxi Medical University, Taiyuan 030001, China; School of Basic Medicine, Basic Medical Science Center, Shanxi Medical University, Jinzhong 030600, China.
Laboratory Animal Center, Shanxi Key Laboratory of Experimental Animal Science and Animal Model of Human Disease, Shanxi Medical University, Taiyuan 030001, China.
J Proteomics. 2021 May 15;239:104186. doi: 10.1016/j.jprot.2021.104186. Epub 2021 Mar 17.
Non-obese, spontaneous, and genetically predisposed type 2 diabetic Chinese hamsters exhibit metabolic abnormalities similar to those observed in human T2DM. Here, tandem mass tag (TMT)-based quantitative proteomics technology was used to screen and identify differentially abundant proteins in the liver that are associated with diabetes in Chinese hamsters. GO and KEGG pathway enrichment analysis were conducted to validate the findings, as well as qRT-PCR and western blotting. In total, 103 proteins were identified in the livers of diabetic hamsters, of which 48 were up-regulated and 55 were down-regulated. KEGG pathway enrichment analysis further demonstrated that linoleic acid metabolism, arachidonic acid metabolism, bile secretion, and other pathways were affected. Moreover, AQP9 and EPHX1 were significantly down-regulated in the bile secretion pathway, whereas PTGES2, Cyp2c27, and Cyp2c70 were associated with the arachidonic acid metabolic pathway. Serum levels of bile acid (BA) and arachidonic acid (AA) in diabetic Chinese hamsters were significantly higher than those in control hamsters. Cumulatively, our findings indicate that the five candidate proteins may be associated with abnormal BA and AA metabolism, suggesting their involvement in pathological changes in the livers of Chinese hamsters with T2DM. SIGNIFICANCE: The liver proteomics of Chinese hamsters describes differentially abundant proteins associated with T2DM, while promoting this animal model as an appropriate and ideal platform for investigating underlying molecular mechanisms of T2DM. This study reveals abnormal bile acid and arachidonic acid metabolism in T2DM hamsters, which may provide insights for studying the relationship between candidate proteins and KEGG pathways to elucidate the underlying molecular mechanism associated with T2DM.
非肥胖、自发性、遗传易患 2 型糖尿病的中国仓鼠表现出与人类 2 型糖尿病相似的代谢异常。在这里,串联质量标签 (TMT)-基于定量蛋白质组学技术用于筛选和鉴定与中国仓鼠糖尿病相关的肝脏中差异丰富的蛋白质。进行 GO 和 KEGG 途径富集分析以验证研究结果,以及 qRT-PCR 和 Western blot。总共在糖尿病仓鼠的肝脏中鉴定了 103 种蛋白质,其中 48 种上调,55 种下调。KEGG 途径富集分析进一步表明,亚油酸代谢、花生四烯酸代谢、胆汁分泌等途径受到影响。此外,AQP9 和 EPHX1 在胆汁分泌途径中显著下调,而 PTGES2、Cyp2c27 和 Cyp2c70 与花生四烯酸代谢途径相关。糖尿病中国仓鼠的血清胆汁酸 (BA) 和花生四烯酸 (AA) 水平明显高于对照仓鼠。总之,我们的研究结果表明,这五种候选蛋白可能与异常 BA 和 AA 代谢有关,表明它们参与了 2 型糖尿病中国仓鼠肝脏的病理变化。意义:中国仓鼠的肝脏蛋白质组学描述了与 2 型糖尿病相关的差异丰富的蛋白质,同时促进了这种动物模型作为研究 2 型糖尿病潜在分子机制的合适和理想平台。本研究揭示了 2 型糖尿病仓鼠中胆汁酸和花生四烯酸代谢异常,这可能为研究候选蛋白与 KEGG 途径之间的关系提供了线索,以阐明与 2 型糖尿病相关的潜在分子机制。