title: The membrane lipid phosphatidylcholine is an unexpected source of triacylglycerol in the liver.
abstract: The increased prevalence of obesity and diabetes in human populations can induce the deposition of fat (triacylglycerol) in the liver (steatosis). The current view is that most hepatic triacylglycerols are derived from fatty acids released from adipose tissue. In this study, we show that phosphatidylcholine (PC), an important structural component of cell membranes and plasma lipoproteins, can be a precursor of ~65% of the triacylglycerols in liver. Mice were injected with [(3)H]PC-labeled high density lipoproteins (HDLs). Hepatic uptake of HDL-PC was ~10 μmol/day, similar to the rate of hepatic de novo PC synthesis. Consistent with this finding, measurement of the specific radioactivity of PC in plasma and liver indicated that 50% of hepatic PC is derived from the circulation. Moreover, one-third of HDL-derived PC was converted into triacylglycerols. Importantly, ~65% of the total hepatic pool of triacylglycerol appears to be derived from hepatic PC, half of which is derived from HDL. Thus, lipoprotein-associated PC should be considered a quantitatively significant source of triacylglycerol for the etiology of hepatic steatosis.
authors.affiliation: Department of Biochemistry and the Group on Molecular and Cell Biology of Lipids, University of Alberta, Edmonton, Alberta T6G 2S2, Canada.
authors.forename: Jelske N
authors.initials: JN
authors.lastname: van der Veen
authors.forename: Susanne
authors.initials: S
authors.lastname: Lingrell
authors.forename: Dennis E
authors.initials: DE
authors.lastname: Vance
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D019916:Choline-Phosphate Cytidylyltransferase / Q000172:deficiency / Q000235:genetics / Q000378:metabolism; D005234:Fatty Liver / Q000097:blood / Q000378:metabolism*; D005260:Female; D006801:Humans; D007527:Isoenzymes / Q000172:deficiency / Q000235:genetics / Q000378:metabolism; D008075:Lipoproteins, HDL / Q000378:metabolism / Q000493:pharmacokinetics; D008099:Liver / Q000378:metabolism*; D008297:Male; D008563:Membrane Lipids / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010713:Phosphatidylcholines / Q000097:blood / Q000378:metabolism* / Q000493:pharmacokinetics; D050918:Phosphatidylethanolamine N-Methyltransferase / Q000172:deficiency / Q000235:genetics / Q000378:metabolism; D051122:Scavenger Receptors, Class B / Q000172:deficiency / Q000235:genetics / Q000378:metabolism; D014280:Triglycerides / Q000378:metabolism*; D014316:Tritium / Q000493:pharmacokinetics
chemical_list: D007527:Isoenzymes; D008075:Lipoproteins, HDL; D008563:Membrane Lipids; D010713:Phosphatidylcholines; C454739:Scarb1 protein, mouse; D051122:Scavenger Receptors, Class B; D014280:Triglycerides; D014316:Tritium; C559160:PEMT protein, mouse; D050918:Phosphatidylethanolamine N-Methyltransferase; D019916:Choline-Phosphate Cytidylyltransferase