Discovery of Novel Lactoyl-Metabolites by Integrating Chemical Isotope Labeling and Knowledge-Based Prediction

-Tmt-aycl-Cl. Using HRMS, 95 lactoyl-metabolites were putatively identified across 14 tissue types, 64 structures of which are reported for the first time. Representative lactoyl-metabolites were chemically synthesized and characterized to verify some of the annotations. We then developed a pseudotargeted metabolomics workflow for semiquantitative profiling in a diabetic kidney disease (DKD) mouse model. DKD mice showed elevated lactate in serum and the kidney and widespread dysregulations of lactoyl-metabolites. Many lactoyl-metabolites correlated strongly with the urinary albumin-to-creatinine ratio, suggesting biomarker potential for DKD. This integrated strategy expands the catalog of lactoyl-metabolites and provides a platform for investigating their biological significance.