Lipid metabolomic changes in liver injury in BTBR ob/ob mice with type 2 diabetes mellitus
10.19405/j.cnki.issn1000-1492.2024.01.013
- Author:
Mingyu Sun
1
;
Wenjing Zhao
2
;
Jing Xin
1
;
Zhiguo Li
2
;
Xiuli Xiuli1
1
Author Information
1. School of Basic Medical Sciences,North China University of Science and Technology,Tangshan 063210
2. School of Public Health,North China University of Science and Technology,Tangshan 063210
- Publication Type:Journal Article
- Keywords:
type 2 diabetes;
liver injury;
metabolomics;
biomarker;
metabolic pathway
- From:
Acta Universitatis Medicinalis Anhui
2024;59(1):77-85
- CountryChina
- Language:Chinese
-
Abstract:
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.
- Full text:2024062416362303272型糖尿病BTBR_ob_...鼠肝损伤的脂质代谢组学变化_孙铭雨.pdf