Wopereis Suzan, Rubingh Carina M, van Erk Marjan J, Verheij Elwin R, van Vliet Trinette, Cnubben Nicole H P, Smilde Age K, van der Greef Jan, van Ommen Ben, Hendriks Henk F J
Department Quality of Life, TNO, Zeist, the Netherlands.
PLoS One. 2009;4(2):e4525. doi: 10.1371/journal.pone.0004525. Epub 2009 Feb 26.
The prevalence of overweight is increasing globally and has become a serious health problem. Low-grade chronic inflammation in overweight subjects is thought to play an important role in disease development. Novel tools to understand these processes are needed. Metabolic profiling is one such tool that can provide novel insights into the impact of treatments on metabolism.
To study the metabolic changes induced by a mild anti-inflammatory drug intervention, plasma metabolic profiling was applied in overweight human volunteers with elevated levels of the inflammatory plasma marker C-reactive protein. Liquid and gas chromatography mass spectrometric methods were used to detect high and low abundant plasma metabolites both in fasted conditions and during an oral glucose tolerance test. This is based on the concept that the resilience of the system can be assessed after perturbing a homeostatic situation.
Metabolic changes were subtle and were only detected using metabolic profiling in combination with an oral glucose tolerance test. The repeated measurements during the oral glucose tolerance test increased statistical power, but the metabolic perturbation also revealed metabolites that respond differentially to the oral glucose tolerance test. Specifically, multiple metabolic intermediates of the glutathione synthesis pathway showed time-dependent suppression in response to the glucose challenge test. The fact that this is an insulin sensitive pathway suggests that inflammatory modulation may alter insulin signaling in overweight men.
超重的患病率在全球范围内呈上升趋势，并已成为一个严重的健康问题。超重受试者的低度慢性炎症被认为在疾病发展中起重要作用。需要新的工具来了解这些过程。代谢谱分析就是这样一种工具，它可以为治疗对代谢的影响提供新的见解。
为了研究一种轻度抗炎药物干预引起的代谢变化，对炎症血浆标志物C反应蛋白水平升高的超重人类志愿者进行了血浆代谢谱分析。采用液相和气相色谱质谱法在空腹条件下和口服葡萄糖耐量试验期间检测高丰度和低丰度血浆代谢物。这是基于这样一个概念，即在扰动稳态情况后可以评估系统的恢复力。
代谢变化很细微，只有通过代谢谱分析结合口服葡萄糖耐量试验才能检测到。口服葡萄糖耐量试验期间的重复测量提高了统计效力，但代谢扰动也揭示了对口服葡萄糖耐量试验有不同反应的代谢物。具体而言，谷胱甘肽合成途径的多种代谢中间产物在葡萄糖激发试验中表现出时间依赖性抑制。这是一条胰岛素敏感途径这一事实表明，炎症调节可能会改变超重男性的胰岛素信号传导。
