| Modern epidemiology and clinical studies have found that high fat intake can increase blood lipid levels,leading to a series of cardiovascular and cerebrovascular diseases and tissue damage,such as hyperlipidemia,non-alcoholic fatty liver disease,diabetes,chronic neuropathy,and atherosclerosis.Triglyceride(TG)fish oil has important significance in preventing cardiovascular and cerebrovascular diseases,improving oxidative stress of fatty liver,reducing insulin resistance,and anti-inflammatory effects,which can help improve cardiovascularrelated diseases caused by high-fat diet.In this study,TG type fish oil was used as the research object,and ethyl ester type(EE)type fish oil was used as the control.The effects of TG type fish oil on the lipid distribution of key target organs in mice fed a high fat diet were analyzed using lipomics.The molecular mechanism of regulating liver lipid metabolism abnormalities by TG type fish oil was explored using metabolomics and transcriptomics studies.1.A mouse model of hyperlipidemia(HLP)was established by feeding high fat diet.The distribution of lipid metabolites in the heart,liver,kidney,and brain of hyperlipidemia rats was regulated by TG type fish oil and EE type fish oil through lipoomic analysis.It was found that the distribution of lipids in the liver and heart changed significantly,and TG type fish oil had the most significant regulatory effect on lipid metabolites in the liver of hyperlipidemia rats.The main lipid metabolic pathway was glycerol phospholipid metabolism,and the lipid biomarker was phosphatidylethanolamine Phosphatidyl choline.2.Through HE and oil red O staining of liver tissue to observe the pathological damage and lipid accumulation of non alcoholic fatty liver disease(NAFLD)caused by HLP complications,it was found that TG fish oil intervention can significantly reduce the inflammatory infiltration,cell hypertrophy,and lipid accumulation of NAFLD hepatocytes caused by high fat diet.Using the metabolomics method of UPLC-QTOF-MS and multivariate statistical analysis of the composition and changes of metabolites,it was found that the key metabolic pathways for TG type fish oil to regulate NAFLD caused by a high fat diet are steroid hormone biosynthesis and unsaturated fatty acid metabolism,with potential biomarkers of 17α-hydroxypregnenolone,cortisol,estrone sulfate,tetrahydrocortisol,docosahexaenoic acid,eicosapentaenoic acid,arachidonic acid,linoleic acid.3.Using RNA-seq technology to analyze the level of differential gene expression in mouse liver,further study the regulatory mechanism of TG type fish oil on NAFLD.It was found that TG type mainly improves NAFLD by regulating signal pathways involved in 5-hydroxytryptaminergic synapses,steroid hormone biosynthesis,linoleic acid,fatty acid biosynthesis,and fatty acid biosynthesis.Through molecular docking,it was verified that the main components of TG type fish oil,DHA and EPA,can regulate lipid metabolism by binding to receptor proteins targeting Gsta2.The results provide new theoretical support for further research on the improvement of NAFLD caused by high fat diet with TG type fish oil. |