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

Abstract

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.

Keywords: DPPIV; Glucose; Malic acid; Palmitic acid.