Abstract:Objective To delve into the effects of prolonged arsenic exposure on brown adipose tissue (BAT) through the application of pseudo-targeted lipidomics. Methods Firstly, a chronic exposure model to arsenic lasting 14 months was established in C57BL/6 mice. Next, the interscapular BAT was subjected to non-targeted lipidomic profiling using ultra high performance liquid chromatography coupled to quadrupole-orbitrap high resolution mass spectrometry. Subsequently, the differential metabolites were identified through the application of multivariate statistical analysis and were vividly represented using volcanic plot visualization techniques. These metabolites were then validated by ultra high performance liquid chromatography quadrupole trap tandem mass spectrometry in multiple reaction monitoringinformation dependent acquisition-enhanced product ion mode, thereby establishing a pseudo-targeted lipidomicapproach for detecting arsenic-exposed BAT. Finally, the mechanisms of arsenics impact on BAT metabolism were explored through multivariate statistical analysis. Results After long-term exposure to arsenic, phosphatidyl ethanolamine, lysophosphatidyl ethanolamine, phosphatidylcholine, lysophosphatidylcholine, phosphatidylglycerol, lysophosphatidylglycerol, phosphatidylinositol, cardiolipin, monolysophospholipin, fatty acid, carnitine and ceramide levels were significantly higher (P < 0.05), with cardiolipin showing the most pronounced increase (5.9-fold). A total of 70 distinct metabolites, mainly glycerophospholipids (43 kinds) and fatty acyl (16 kinds), were accurately screened by means of pseudotargeted lipidomic. KEGG pathway enrichment analysis indicated that the differential metabolites in arsenic-exposed BAT were chiefly associated with the glycerophospholipid metabolism and unsaturated fatty acid metabolism pathways. Conclusion Long-term exposure to arsenic mainly leads to metabolic disorders of glycerophospholipids and unsaturated fatty acids in BAT.
