Department of Biotechnology, Daegu University, Kyungsan, Kyungbuk, Republic of Korea.
Proteomics. 2011 Apr;11(7):1300-12. doi: 10.1002/pmic.201000664. Epub 2011 Feb 17.
Sibutramine is an anti-obesity agent that induces weight loss by selective inhibition of neuronal reuptake of serotonin and norepinephrine; however, it is associated with the risk of cardiovascular diseases (CVD), including heart attack and stroke. Here, we analyzed global protein expression patterns in plasma of control and sibutramine-treated rats using proteomic analysis for a better understanding of the two conflicting functions of this drug, appetite regulation, and cardiovascular risk. The control (n=6) and sibutramine-treated groups (n=6) were injected by vehicle and sibutramine, respectively, and 2-DE combined with MALDI-TOF/MS were performed. Compared to control rats, sibutramine-administered rats gained approximately 18% less body weight and consumed about 13% less food. Plasma leptin and insulin levels also showed a significant decrease in sibutramine-treated rats. As a result of proteomic analysis, 23 differentially regulated proteins were discovered and were reconfirmed by immunoblot analysis. Changed proteins were classified into appetite regulation and cardiovascular risk, according to their regulation pattern. Because the differential levels of proteins that have been well recognized as predictors of CVD risk were not well matched with the results of our proteomic analysis, this study does not conclusively prove that sibutramine has an effect on CVD risk.
西布曲明是一种减肥药，通过选择性抑制神经元对 5-羟色胺和去甲肾上腺素的再摄取来诱导体重减轻；然而，它与心血管疾病（CVD）的风险相关，包括心脏病发作和中风。在这里，我们使用蛋白质组学分析分析了对照和西布曲明处理的大鼠血浆中的全球蛋白质表达模式，以更好地理解这种药物的两种相互冲突的功能，即食欲调节和心血管风险。对照组（n=6）和西布曲明处理组（n=6）分别用载体和西布曲明注射，然后进行 2-DE 结合 MALDI-TOF/MS。与对照组大鼠相比，西布曲明给药大鼠体重减轻约 18%，食物摄入量减少约 13%。血浆瘦素和胰岛素水平在西布曲明处理的大鼠中也显著降低。蛋白质组学分析发现了 23 个差异调节蛋白，并通过免疫印迹分析进行了重新确认。根据其调节模式，将变化的蛋白质分为食欲调节和心血管风险。由于差异水平的蛋白质已被公认为 CVD 风险的预测因子，与我们的蛋白质组学分析结果不匹配，因此本研究不能确定地证明西布曲明对 CVD 风险有影响。
