Disruption of PPARβ results in distinct gender differences in mouse brain phospholipid

Abstract

A homozygous PPARβ‐null mouse has been developed in which the ligand‐binding domain of the PPARβ receptor is disrupted. Analysis of brains from these animals show that female null mice have a 24 and 17% increase of plasmenylethanolamine and phosphatidylserine and a 9% decrease in the level of phosphatidylinositol when compared to controls. The phospholipid changes found in female null mice were associated with significant increases in esterified 18:1n‐9, 20:1n‐9, 20:4n‐6, and 22:5n‐3 in plasmenylethanolamine, 20:1n‐9 in phosphatidylinositol, and 18:0, 18:1n‐9, 18:3n‐6, 20:1n‐9, and 20:4n‐6 in phosphatidylserine. Increased esterified 18:1n‐9, 18:2n‐6, 18:3n‐6, and 20:1n‐9 were also found in the phosphatidylethanolamine fraction despite its cellular content remaining unchanged. Brain phospholipid content in male PPARβ‐null mice was not different than controls, but increased levels of 20:1n‐9 in the phosphatidylinositol and 18:1n‐9 in the phosphatidylserine fractions were observed. No changes were found in the content of brain cholesterol, triglycerides, and free fatty acid in either female or male PPARβ‐null mice. These data suggests that the peroxisomal proliferator‐activated receptor beta is involved in maintaining fatty acid and phospholipid levels in adult female mouse brain and provides strong evidence suggesting a role for PPARβ in peroxisomal acyl‐CoA utilization.