Liver lipid profiling of chemical‐induced phospholipidosis

Abstract

Lipids play important roles in multiple biological processes and its disorder is well associated with diseases and injuries. Thus, lipid profiling would be a useful to understand pathophysiology of but also to identify biomarker for chemical‐induced phospholipidosis. In the present study, we used rat model to overview liver lipid profiles of two types of phospholipidosis. Hepatic phospholipidosis were induced by treatment of clomipramine (CPM), imipramine (IMI), amitriptyline (AMT) and ketoconazole (KC) for 28 days. Phospholipidosis were determined by histopathological evaluation. CPM, IMI and AMT induced phospholipidosis in hepatocyte, while KC induced phospholipidosis in bile duct. To overview liver lipid profiles, we employed recently developed lipidomics platform with liquid chromatography and mass spectrometry (LC/MS), whic hsimultaneously determine the levels of broad spectrum of lipids. In total, we determined and examined 138 lipids (62 phospholipids, 10 sphingolipids and 65 neutral lipids). Each chemical treatment have their corresponding control treated with vehicle. To identify specific lipid alterations in the liver, we employed multivariate orthogonal partial least squares discriminant analysis. A bis‐monophosphatidic acid (BMP) (BMP[44:12]) and several triacylglycerols (TGs) were identified as specific lipids separating control and chemical‐treated rats in all models of phospholipidosis in the liver. The levels of BMP(44:12) were increased in the liver by chemical‐induced phospholipidosis. On the other hand, several TGs were increased in the liver by CPM, IMI and AMT but decreased by KC. Therefore, increased levels of BMP is common features of hepatic phospholipidosis and alteration of TGs might be associated with zone‐specific events in the liver. Our study provides the new insight into the alteration of liver lipidprofiles which probably reflecting chemical‐induced hepatic phospholipidosis and may help to understand its pathophysiology.Support or Funding InformationThis work was supported by the intramural research grant of National Institute of Health Sciences and the Health and Labour Sciences Research Grants (Grantnumber H028) from the Ministry of Health, Labour and Welfate of Japan.