PR002430 (Project)

Description:Ether lipids are major constituents of biomembranes and often contain polyunsaturated fatty acids at the sn-2 position, implicating them in cellular signaling and inflammatory processes. Alkylglycerol monooxygenase is the only enzyme capable of cleaving alkylglycerols, an ether lipid subclass, but its exact role and that of its substrates remain unclear. Here, we demonstrate a sex- and cell type-dependent role of alkylglycerol monooxygenase in limiting prostanoid formation without affecting polyunsaturated fatty acid release, as revealed by metabololipidomics profiling. This female-specific effect is driven by the suppression of prostaglandin G/H synthase 2 transcription, as deficiency in alkylglycerol monooxygenase significantly elevated prostaglandin G/H synthase 2 expression in female bone marrow-derived macrophages of the M1 phenotype. Furthermore, this regulatory role of alkylglycerol monooxygenase extends to visceral white adipose tissue, where elevated prostaglandin G/H synthase 2 expression and enhanced prostaglandin production were observed in female samples following alkylglycerol monooxygenase knockout. Collectively, our results expand the immunomodulatory functions of ether lipid metabolism and highlight the role of alkylglycerol monooxygenase in controlling lipid mediator production and maintaining tissue homeostasis.