| OBJECTIVE:In view of the importance of lipid abnormalities in the pathogenesis of insulin resistance(IR),this study aimed to simulate the clinical administration mode and dose of olanzapine induced IR on Sprague-Dawley(SD)rats and explore the changes of the central and peripheral lipid profiles in SD rats to search the possible lipid molecular markers related to the metabolic side effects of olanzapine.Then,we examined differences of abnormal lipid molecules with the intervention of metformin and deduce the mechanism of IR.METHODS:Using olanzapine to induce IR in SD rats,intraperitoneal glucose tolerance test(IGTT)and homeostasis model assessment insulin resistance(HOMA-IR)as the assessment indexes of IR.Then,combined with metformin,analyzing the changes of lipid profiling in serum and brain tissue by the high performance liquid chromatography-time of flight mass spectrometry technology.RESULTS:HOMA-IR in olanzapine group was significantly higher than control group(T=8.929,P=0.000),IGTT in the olanzapine group was significantly different from the control group(F = 6.577,P = 0.019),the rats were successfully induced to produce IR.Then metformin was used as intervention,after screening by the method of lipidomics,a total of 13 species of differential lipid metabolites were detected,5 of them in serum,7 in hypothalamus and 1 in hippocampus,respectively.Among these lipid molecules,DG36:2(+H-H2O),DG36:2(+NH4),DG34:1,TG54:1,Palmitic acid,Docosahexaenoic acid and PS(49:6)may be potential markers of olanzapine induced IR.CONCLUSION:This study utilized lipidomics to measure central and peripheral samples of olanzapine-induced IR rats at the same time,some significant differences in lipid molecules were founded indeed when there was IR induced by olanzapine.They may be possible markers for IR and were involved in some neurotransmitters and their receptor processes,energy generation and inflammation. |
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