The Membrane Lipid Phosphatidylcholine Is an Unexpected Source of Triacylglycerol in the Liver

• Published in: The Journal of biological chemistry 2012-07, Vol.287 (28), p.23418-23426
• Main Authors: van der Veen, Jelske N., Lingrell, Susanne, Vance, Dennis E.
• Format: Article
• Language: English
• Subjects: Animals; Biosynthesis; Cell Line, Tumor; Cells, Cultured; Choline-Phosphate Cytidylyltransferase - deficiency; Choline-Phosphate Cytidylyltransferase - genetics; Choline-Phosphate Cytidylyltransferase - metabolism; Fatty Liver - blood; Fatty Liver - metabolism; Female; High Density Lipoprotein (HDL); Humans; Isoenzymes - deficiency; Isoenzymes - genetics; Isoenzymes - metabolism; Lipids; Lipoproteins, HDL - metabolism; Lipoproteins, HDL - pharmacokinetics; Liver; Liver - metabolism; Male; Membrane Lipids - metabolism; Mice; Mice, Inbred C57BL; Mice, Knockout; Phosphatidylcholine; Phosphatidylcholines - blood; Phosphatidylcholines - metabolism; Phosphatidylcholines - pharmacokinetics; Phosphatidylethanolamine N-Methyltransferase - deficiency; Phosphatidylethanolamine N-Methyltransferase - genetics; Phosphatidylethanolamine N-Methyltransferase - metabolism; Scavenger Receptors, Class B - deficiency; Scavenger Receptors, Class B - genetics; Scavenger Receptors, Class B - metabolism; Triacylglycerol; Triglycerides - metabolism; Tritium - pharmacokinetics
• ISSN: 0021-9258; 1083-351X
• DOI: 10.1074/jbc.M112.381723

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 [3H]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. Background: Most hepatic triacylglycerols are believed to originate from fatty acids released from adipose tissue. Results: Lipoprotein phosphatidylcholine is taken up by the liver and converted into triacylglycerols in vivo. Conclusion: Lipoprotein-associated phosphatidylcholine is a quantitatively significant source of hepatic triacylglycerols. Significance: The role of lipoprotein phosphatidylcholine should now be factored into our thinking about the development of hepatic steatosis.