Integrated plasma metabolomics and lipidomics profiling highlight distinctive signatures with hashimoto's thyroiditis

Hashimoto's Thyroiditis (HT) is an autoimmune disorder characterized by metabolic disturbances. However, a comprehensive metabolic and lipid profile of HT has not been reported. The metabolic and lipid profile of HT can be comprehensively analyzed through metabolomics and lipidomics technologies, providing a detailed understanding of the disease's biochemical alterations. Plasma samples were obtained from 20 mice, comprising 10 from the control group and 10 from the HT group. Plasma metabolomics and lipidomics were analyzed via LC-MS/MS. PCA, PLS-DA, and OPLS-DA of the preprocessed data matrix were conducted using the ropls package (V.1.6.2) in R. The identification of significant differential metabolites was based on the VIP scores in the OPLS-DA model and p-values (Student's t-test). Metabolites (VIP exceeding 1 and p < 0.05) were classified as significantly different. Pathway annotation of these metabolites was carried out using the KEGG database to identify associated metabolic pathways. Pathway enrichment analysis was performed using the Python scipy. Stats package, with Fisher's exact test employed to identify biological pathways most relevant to the experimental conditions. Metabolomics identified 6384 metabolites (2943 in positive ion mode and 3441 in negative), with 195 differential metabolites, comprising 114 upregulated and 81 downregulated in the HT group. Lipidomics analysis revealed 1054 lipid metabolites (695 detected in positive ion mode and 359 in negative), and 247 differentially expressed lipids were identified, including 165 upregulated and 82 downregulated in the HT group. KEGG enrichment analysis indicated that metabolites upregulated in the HT group were primarily associated with pathways such as Autophagy, Choline metabolism, PPAR signaling, and Glycerophospholipid metabolism. In contrast, pathways involved in Apoptosis, Cholesterol metabolism, Sphingolipid metabolism, EGFR tyrosine kinase inhibitor resistance, Th1 and Th2 cell differentiation, viral infection, and Chemokine signaling were suppressed. Metabolic and lipidomic dysregulation was observed in HT animal models, with pronounced alterations in Phospholipids, Eicosanoids, and Carnitines. Choline, Glycerophospholipid, and Linoleic acid metabolism pathways exhibited significant enrichment in HT.