Tissue-dependent alterations in lipid mass in mice lacking glycerol kinase.
Glycerol kinase (ATP:glycerol-3-phosphotransferase, EC 2.7.1.30, glycerokinase) (Gyk) has a central role in plasma glycerol extraction and utilization by tissues for lipid biosynthesis. Gyk deficiency causes various phenotypic changes ranging from asymptomatic hyperglycerolemia to a severe metabolic disorder with growth and psychomotor retardation. To better understand the potential role of Gyk in tissue lipid metabolism, we determined phospholipid (PL), cholesterol (Chol), and triacylglycerol (TG) mass in a number of tissues from mice lacking Gyk. We report a tissue-dependent response to Gyk gene deletion. Tissues with elevated total PL mass (brain, kidney, muscle) were characterized by the increased mass of ethanolamine glycerophospholipids (EtnGpl), choline glycerophospholipids, and phosphatidylserine (PtdSer). In heart, lipid changes were characterized by a reduction in total PL, including decreased EtnGpl, phosphatidylinositol, and PtdSer mass and decreased TG and FFA mass. In parallel with tissue PL alterations, tissue Chol was also changed, maintaining a normal Chol/PL ratio. Under conditions of Gyk deficiency, we speculate that glycerol-3-phosphate and lipid production is maintained via alternative biosynthesis, including glycolysis, glyceroneogenesis, or by direct acylation of glycerol in brain, muscle, kidney, and liver, but not in heart.
Golovko
Mikhail Y
MY
Department of Pharmacology, University of North Dakota, Grand Forks, North Dakota 58202-9037, USA.
Hovda
Johnathan T
JT
Cai
Zong-Jin
ZJ
Craigen
William J
WJ
Murphy
Eric J
EJ
D000273:Adipose Tissue / Q000033:anatomy & histology*; D000818:Animals; D001923:Brain Chemistry; D002784:Cholesterol / Q000032:analysis*; D018390:Gene Targeting; D005991:Glycerol Kinase / Q000172:deficiency* / Q000235:genetics / Q000378:metabolism; D007668:Kidney / Q000737:chemistry; D008099:Liver / Q000737:chemistry; D051379:Mice; D018345:Mice, Knockout; D018482:Muscle, Skeletal / Q000737:chemistry; D009206:Myocardium / Q000737:chemistry; D009929:Organ Size; D009928:Organ Specificity; D010743:Phospholipids / Q000032:analysis*; D012016:Reference Values
D010743:Phospholipids; D002784:Cholesterol; D005991:Glycerol Kinase