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首页> 美国卫生研究院文献>International Journal of Molecular Sciences >Proteomic Identification of Target Proteins of Thiodigalactoside in White Adipose Tissue from Diet-Induced Obese Rats
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Proteomic Identification of Target Proteins of Thiodigalactoside in White Adipose Tissue from Diet-Induced Obese Rats

机译：饮食诱导肥胖大鼠白色脂肪组织中硫三全糖苷目标蛋白的蛋白质组学鉴定

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摘要

Previously, galectin-1 (GAL1) was found to be up-regulated in obesity-prone subjects, suggesting that use of a GAL1 inhibitor could be a novel therapeutic approach for treatment of obesity. We evaluated thiodigalactoside (TDG) as a potent inhibitor of GAL1 and identified target proteins of TDG by performing comparative proteome analysis of white adipose tissue (WAT) from control and TDG-treated rats fed a high fat diet (HFD) using two dimensional gel electrophoresis (2-DE) combined with MALDI-TOF-MS. Thirty-two spots from a total of 356 matched spots showed differential expression between control and TDG-treated rats, as identified by peptide mass fingerprinting. These proteins were categorized into groups such as carbohydrate metabolism, tricarboxylic acid (TCA) cycle, signal transduction, cytoskeletal, and mitochondrial proteins based on functional analysis using Protein Annotation Through Evolutionary Relationship (PANTHER) and Database for Annotation, Visualization, Integrated Discovery (DAVID) classification. One of the most striking findings of this study was significant changes in Carbonic anhydrase 3 (CA3), Voltage-dependent anion channel 1 (VDAC1), phosphatidylethanolamine-binding protein 1 (PEBP1), annexin A2 (ANXA2) and lactate dehydrogenase A chain (LDHA) protein levels between WAT from control and TDG-treated groups. In addition, we confirmed increased expression of thermogenic proteins as well as reduced expression of lipogenic proteins in response to TDG treatment. These results suggest that TDG may effectively prevent obesity, and TDG-responsive proteins can be used as novel target proteins for obesity treatment.
机译：以前，发现半乳糖凝集素-1（GAL1）在易发肥胖的受试者中被上调，这表明使用GAL1抑制剂可能是治疗肥胖的一种新颖治疗方法。我们通过使用二维凝胶电泳对高脂饮食（HFD）的对照和TDG处理的大鼠进行白色脂肪组织（WAT）的比较蛋白质组分析，从而评估了硫代三糖苷（TDG）作为GAL1的有效抑制剂，并确定了TDG的靶蛋白。 （2-DE）与MALDI-TOF-MS组合。通过肽质量指纹图谱鉴定，在总共356个匹配点中，有32个点在对照和TDG处理的大鼠之间显示出差异表达。根据使用蛋白质进化关系注释法（PANTHER）和注释，可视化，综合发现数据库（DAVID）进行的功能分析，将这些蛋白质分为碳水化合物代谢，三羧酸（TCA）循环，信号转导，细胞骨架和线粒体蛋白质等类别。 ）分类。这项研究最引人注目的发现之一是碳酸酐酶3（CA3），电压依赖性阴离子通道1（VDAC1），磷脂酰乙醇胺结合蛋白1（PEBP1），膜联蛋白A2（ANXA2）和乳酸脱氢酶A链（对照和TDG处理组的WAT之间的LDHA）蛋白水平。此外，我们证实响应TDG处理，产热蛋白表达增加，而产脂蛋白表达减少。这些结果表明，TDG可以有效预防肥胖，并且TDG反应蛋白可以用作肥胖治疗的新型靶蛋白。

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