Profile of cardiac lipid metabolism in STZ-induced diabetic mice

Lipotoxicity contributes to diabetic myocardial disease. In this study, we investigated the lipid species contributing to lipotoxicity and the relationship with peroxisomal β-oxidation in the heart of diabetic mice. Male C57BL/6 mice were randomly divided into a Diabetic group (intraperitoneal injection of STZ) and a Control group (saline). Cardiac function indexes [ejection fraction (EF%) and fractional shortening (FS%)] were evaluated by echocardiography. Morphological changes in the myocardial tissues and mitochondria were assessed by electron microscopy following hematoxylin and eosin staining. Blood myocardial injury indexes and lipids were measured using an automatic biochemical analyzer. Cardiac ATP levels were analyzed using a commercially available kit. mRNA levels of glucose transporter 4 (GLUT4), fatty acid binding protein 3 (FABP3), palmitoyl transferase 1α (CPT-1α), acyl-CoA oxidase 1 (AOX1), D-bifunctional protein (DBP), 3-ketoacyl-CoA thiolase A (THLA), uncoupling protein (UCP) 2 and UCP3 were investigated by quantitative reverse-transcription polymerase chain reaction. FABP3 protein expression was analyzed by Western blotting. Non-targeted metabolomics by LC-MS/MS was applied to evaluate profile of lipid metabolism in heart. Compared with controls, EF% and FS% were significantly reduced in diabetic mice. Furthermore, blood myocardial injury indexes and lipids, as well as myocardial mitochondrial cristae fusion were significantly increased. In the diabetic heart, GLUT4 expression was decreased, while expression of FABP3, CPT-1α, AOX1, DBP, THLA, UCP2 and UCP3 was increased, and ATP levels were reduced. In total, 113 lipids exhibited significant differential expression (FC > 2, P