Metabolic profiling of the response to an oral glucose tolerance test detects subtle metabolic changes

• Published in: PloS one 2009-02, Vol.4 (2), p.e4525-e4525
• Main Authors: 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
• Format: Article
• Language: English
• Subjects: Anti-inflammatory agents; Biomarkers; Blood Glucose - physiology; Body mass index; Body weight; C-Reactive Protein; Cardiovascular disease; Change detection; Chromatography; Diabetes; Endocrinology; Family medical history; Fasting; Gas chromatography; Genetics and Genomics/Bioinformatics; Genetics and Genomics/Functional Genomics; Glucose; Glucose tolerance; Glucose Tolerance Test; Glutathione; Homocysteine; Humans; Hypertension; Inflammation; Insulin; Intermediates; Lifestyles; Male; Mass Spectrometry; Metabolic Networks and Pathways; Metabolic syndrome; Metabolism; Metabolites; Metabolome; Nonsteroidal anti-inflammatory drugs; Nutrition research; Nutrition/Deficiencies; Obesity; Overweight; Physiology; Plasmas (physics); Profiling; Proteins; Quality; Quality of life; Rheumatic diseases; Spectrometry; Uric acid
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0004525

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.