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Targeted disruption of peroxisomal proliferator‐activated receptor β (δ) results in distinct gender differences in mouse brain phospholipid and esterified FA levels
Author(s) -
Rosenberger Thad A.,
Hovda Jonathan T.,
Peters Jeffrey M.
Publication year - 2002
Publication title -
lipids
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.601
H-Index - 120
eISSN - 1558-9307
pISSN - 0024-4201
DOI - 10.1007/s11745-002-0923-1
Subject(s) - phosphatidylserine , phosphatidylinositol , phospholipid , receptor , medicine , endocrinology , phosphatidylethanolamine , biology , peroxisome , lipid metabolism , nuclear receptor , chemistry , biochemistry , phosphatidylcholine , transcription factor , signal transduction , gene , membrane
The peroxisomal proliferator‐activated receptor β (δ) (PPARβ) is a nuclear hormone receptor that is ubiquitously expressed and that regulates the transcription of genes involved in lipid metabolism. 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 shows that female null mice have 24 and 17% increases in 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 increased levels of esterified 18∶1n−9, 20∶1n−9, 20∶4n−6, and 22∶5n−3 FA 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 levels of 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 did not differ from 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, TAG, and FFA in either female or male PPARβ‐null mice. These data suggest that PPARβ is involved in maintaining FA and phospholipid levels in adult female mouse brain and provide strong evidence that suggests a role for PPARβ in brain peroxisomal acyl‐CoA utilization.