摘要
Objective @#To investigate the changes of lipid biomarkers and lipid metabolic pathways related to liver injury in BTBR ob/ob mice with type 2 diabetes mellitus by biochemical and metabolomics methods．@*Methods @# 16 BTBR wild-type (WT) mice (WT group) and 14 BTBR ob/ob obese mice (ob / ob group) at 7 weeks of age were selected and fed in SPF environment until 20 weeks of age．Liver injury was compared between the two groups : The activities of mitochondrial respiratory enzyme complex in liver tissue were detected by high-resolution respirators，and the lipid metabolomic analysis of liver tissue samples in the two groups of mice was performed by ultra-perform- ance liquid chromatography-quadrupole time-of-flight mass spectrometry，mainly detecting endogenous metabolites. Principal component analysis (PCA) ，orthogonal partial least squares discriminant analysis ( OPLS-DA) and other models were used to screen potential biomarkers，and the metabolic pathway analysis of the identified metabolites was performed by MetaboAnalyst 5. 0 . @*Results @#Compared with the WT group，the ob / ob group had significantly increased body weight，fasting blood glucose ，serum levels of aspartate aminotransferase ( AST) ，alanine amin- otransferase (ALT) ，low-density lipoprotein (LDL-C) and cholesterol ( CHO) (P＜0. 01) ．Liver hematoxylin-eo- sin staining (HE) staining showed that the mice in ob / ob group had structural disorder of liver lobules，swelling of liver cells ，a large number of fat vacuoles in cells ，diffuse distribution and loose cytoplasm． Oil red O staining showed that there was a large amount of lipid deposition in the hepatocytes ofob/ob mice．The high resolution spi- rometer showed that the ob/ob mice had mitochondrial oxidative phosphorylation disorder and the activity of complex Ⅳ decreased．Lipid metabolomic analysis showed that the lipid metabolic profile of ob/ob mice changed，and the metabolic pathways involved mainly included glycerophospholipid metabolism，glycosylphosphatidylinositol ( GPI) anchor biosynthesis，triglyceride metabolism，linoleic acid metabolism，α-linolenic acid metabolism and arachidon- ic acid metabolism．@*Conclusion @#The liver injury of ob / ob group mice may be related to the disorder of lipid me- tabolism，in which the disorder of glycerophospholipid metabolism is the most critical metabolic pathway.