The characterization of metabolites alterations in white adipose tissue of diabetic GK Rats after ileal transposition surgery by an untargeted metabolomics approach

Dysfunction of adipose tissue could lead to insulin resistance, obesity and type 2 diabetes. Thus, our present study aimed to investigate metabolites alterations in white adipose tissue (WAT) of diabetic GK rats after IT surgery. Ten-week-old male diabetic GK rats were randomly subjected to IT and Sham-IT surgery. Six weeks later, the untargeted metabolomics in WAT of diabetic GK rats was performed. Differential metabolites were selected according to the coefficient of variation (CV) of quality control (QC) sample <30%, variable importance in the projection (VIP) >1 and P < 0.05. Then, the hierarchical clustering of differential metabolites was conducted and the KEGG database was used for metabolic pathway analysis. A total of 50 (in positive ion mode) and 68 (in negative ion mode) metabolites were identified as differential metabolites in WAT of diabetic GK rats between IT group and Sham-IT group, respectively. These differential metabolites were well clustered, which in descending order of the number of involved differential metabolites is ubiquinone and other terpenoid-quinone biosynthesis, AMPK signalling pathway, pantothenate and CoA biosynthesis, ferroptosis, vitamin digestion and absorption, glycerophospholipid metabolism, phenylalanine metabolism, steroid hormone biosynthesis, neuroactive ligand–receptor interaction, porphyrin and chlorophyll metabolism and bile secretion, and correlated with the parameters of body weight, food intake, WAT mass and glucose metabolism, which were significantly improved after IT surgery. The differential metabolites in WAT of diabetic GK rats were mainly related to the pathway of energy metabolism, and correlated with the improved phenotypes of diabetic GK rats after IT surgery.