Hormone-sensitive lipase deficiency disturbs lipid composition of plasma membrane microdomains from mouse testis

Hormone-sensitive lipase (HSL) is an intracellular neutral lipase capable of hydrolyzing acylglycerols, as well as cholesteryl and retinyl esters. In mice, HSL deficiency results in male sterility. Lipid rafts, a plasma membrane microdomain enriched in cholesterol, sphingolipids and saturated glycerophospholipids, comprise a highly dynamic clustering of proteins and lipids that play a central role in signal transduction and intercellular communication. In the present work, we examined the effect of HSL deficiency in the lipid composition of plasma membrane microdomains in mouse testis. The lack of HSL affected the density of lipid rafts, as indicated by the shifting of caveolin 1 to denser fractions in the sucrose-gradient fractionation, and altered the sterol and phospholipid composition of both lipid raft and non-raft fractions, the biochemical differences among them being less obvious in HSL−/− than in HSL+/+ mice. Compared to HSL+/+, the lipid rafts from HSL−/− mice had significantly less desmosterol and T-MAS, while the non-raft domain had increased cholesterol content. Lipid rafts from HSL−/− mice had reduced PUFA-containing phospholipid species but increased phosphatidylcholine and phosphatidylethanolamine species with monounsaturated fatty acid moieties, while the non-raft domain was enriched in phosphatidylethanolamine and phosphatidylserine species having four double bonds. The changes in both the sterols and phospholipid composition of lipid raft and non-raft microdomains may have consequences in signal transduction and contribute to the sterility observed in HSL-deficient male mice.