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INNOVATIVE METHODOLOGY

Changes of the plasma metabolome during an oral glucose tolerance test: is there more than glucose to look at?

¹Key Laboratory of Separation Science for Analytical Chemistry, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian, China; ²Division of Clinical Chemistry and Pathobiochemistry (Central Laboratory), ⁵Department of Internal Medicine 4, University Hospital Tuebingen, Tuebingen; ³Immatics Biotechnologies, Tuebingen; Germany; and ⁴Department of Analytical Chemistry, Faculty of Chemical Technology, University of Pardubice, Pardubice, Czech Republic

Submitted 14 September 2008 ; accepted in final form 1 December 2008

The oral glucose tolerance test (oGTT) is a common tool to provoke a metabolic challenge for scientific purposes, as well as for diagnostic reasons, to monitor the kinetics of glucose and insulin. Here, we aimed to follow the variety of physiological changes of the whole metabolic pattern in plasma during an oGTT in healthy subjects in a nontargeted reversed-phase ultra performance liquid chromatography coupled to electrospray ionization quadrupole time of flight mass spectrometric metabolomics approach. We detected 11,500 metabolite ion masses/individual. Applying multivariate data analysis, four major groups of metabolites have been detected as the most discriminating oGTT biomarkers: free fatty acids (FFA), acylcarnitines, bile acids, and lysophosphatidylcholines. We found in detail 1) a strong decrease of all saturated and monounsaturated FFA studied during the oGTT; 2) a significant faster decline of palmitoleate (C16:1) and oleate (C18:1) FFA levels than their saturated counterparts; 3) a strong relative increase of polyunsaturated fatty acids in the fatty acid pattern at 120 min; and 4) a clear decrease in plasma C10:0, C12:0, and C14:1 acylcarnitine levels. These data reflect the switch from β-oxidation to glycolysis and fat storage during the oGTT. Moreover, the bile acids glycocholic acid, glycochenodeoxycholic acid, and glycodeoxycholic acid were highly discriminative, showing a biphasic kinetic with a maximum of a 4.5- to 6-fold increase at 30 min after glucose ingestion, a significant decrease over the next 60 min followed by an increase until the end of the oGTT. Lysophosphatidylcholines were also increased significantly. The findings of our metabolomics study reveal detailed insights in the complex physiological regulation of the metabolism during an oGTT offering novel perspectives of this widely used procedure.

metabolomics; metabonomics; oral glucose tolerance test; bile acids; fatty acids; palmitoleate; acylcarnitines; lysophosphatidylcholines