Lipidomics Analysis Deepen Understanding the Molecular Mechanisms in a Gouty Model Induced by Combination of MSU Crystals Injection and High-Fat Diet Feeding and the Intervention Mechanisms of Allopurinol.

Abstract

Gouty arthritis (GA) is a common inflammatory disease caused by deposition of monosodium urate (MSU) crystals in diarthrodial joints. GA attacks commonly involved in joint with red, swollen, heat and pain, and often happened in unilateral foot-first metatarsophalangeal. Accumulated studies have proved that lipids play critical roles in biological processes and lipids biomarkers can substitute for the diagnosis of various diseases. Herein, shotgun lipidomics was used to quantitatively analyze serum lipidomes of a gouty model which was induced by injecting MSU crystals and feeding high-fat diet with/without treatment with allopurinol. Meanwhile, ELISA kit was used to detect mouse serum levels of inflammatory cytokines (eg, tumor necrosis factor-α, interleukin 1 beta) and HE staining was used to observe the infiltration of inflammatory cells in the foot pad. A total of 9 types of serum lipids were detected in lipidomics by shotguns, and the result of NMDS' analysis demonstrated significant differences in lipids profiles between the control and model group. It is worth noting that lipid abnormality in GA (such as Ceramide (Cer), sphingomyelin (SM), 4-hydroxyalkenals (HNE), phosphatidylinositol (PI), ethanolamine glycerophospholipid (PE), etc.) is related with phospholipid and energy metabolism, and allopurinol treatment could correct the aberrant metabolism of lipid to some extent. Our results indicated that various aberrant lipid metabolisms were present in the established gouty model, and allopurinol treatment could relief this aberrant metabolism of lipids to some degree.