Advanced lipidomics using UHPLC-ESI-QTOF-MS/MS reveals novel lipids in hibernating syrian hamsters

Abstract

Mammalian hibernation offers a unique model for exploring neuroprotective mechanisms relevant to neurodegenerative diseases. In this study, we employed untargeted lipidomics with iterative tandem mass spectrometry (MS/MS) to profile the brain lipidome of Syrian hamsters across different hibernation stages: late torpor, arousal, and euthermia (control). Previously, a lipid species identified as methyl-PA(16:0/0:0) showed a significant increase during torpor, but its precise structure was unresolved due to technological constraints. Leveraging iterative MS/MS and advanced lipid annotation tools (LipidAnnotator and MS-DIAL), we accurately annotated 377 lipid species, including the re-identification of methyl-PA(16:0/0:0) as methylated lysophosphatidic acid (PMeOH 16:0/0:0). This reannotation led to the discovery of two additional lipids during torpor: PMeOH 18:0/0:0 and PMeOH 18:1/0:0. Verification involved manual inspection of MS/MS spectra and Kendrick Mass Defect plots. The lipid alterations observed during torpor suggest biochemical adaptations to maintain membrane fluidity and protect against oxidative stress under hypothermic conditions. Elevated levels of PMeOH lipids and their lyso-forms may play roles in cell survival signalling. Additionally, a decrease in phosphatidic acid species and an increase in diacylglycerol species imply a metabolic shift favouring diacylglycerol production, potentially activating protein kinase C signalling pathways. The increased levels of monogalactosyl diglyceride lipids during torpor suggest a role in neuroprotection by enhancing oligodendrocyte function and myelination. Our comprehensive lipidomic profiling provides detailed insights into lipid dynamics associated with hibernation and underscores the potential of advanced MS/MS methodologies in lipidomics for developing therapeutic strategies against neurodegenerative diseases.