A GC-MS untargeted metabolomics analysis in the plasma and liver of rats lacking dipeptidyl-peptidase type IV enzyme activity

This study was achieved with the aim to find metabolic changes between Fischer rats with different dipeptidyl peptidase-type 4 (DPPIV) expression. The DPPIV is an enzyme expressed in several tissues and is critically involved in the regulation of meal-related insulin secretion in healthy individuals. The metabolic consequences of chronic DPPIV inhibition were analyzed in a surrogate animal model of genetic enzyme deficiency. Hyphenated gas chromatography–mass spectrometry (GC–MS) and multivariate data analysis techniques were used to study the metabolic aqueous fraction profile of 18 plasma and liver samples in two syngeneic rat strains differing in DPPIV activity (DPPIV+ vs. DPPIV−). The hyperglycemic response following oral glucose administration was attenuated in DPPIV− rats, as expected. Statistical significant differences between the two strains were observed among the low molecular weight polar metabolites analyzed from plasma and liver. These included a decrease in malic acid and glutamine and an increase in pyroglutamic acid, serine, and alanine in plasma of DPPIV− rats. In addition, palmitic acid, l-proline, and ribitol were decreased in the liver of DPPIV− strain. Such alterations were compatible with a normal phenotype. These results suggest that long-term exposure to DPPIV inhibitors looks compatible with an overall balanced metabolism.