A Gender-specific Role For Phosphatidylethanolamine N-Methyltransferase-derived Phosphatidylcholine in the Regulation of Plasma High Density and Very Low Density Lipoproteins in Mice

Phosphatidylethanolamine N-methyltransferase (PEMT)is involved in a secondary pathway for production of phosphatidylcholine (PC) in liver. We fed Pemt–/–mice a high fat/high cholesterol diet for 3 weeks to determine whether or not PC derived from PEMT is required for very low density lipoprotein secretion. Lipid analyses of plasma and liver indicated that male Pemt–/– mice accumulated triacylglycerols in their livers and were unable to secrete the same amount of triacylglycerols from the liver as did Pemt+/+ mice. Plasma levels of triacylglycerol and both apolipoproteins B100 and B48 were significantly decreased only in male Pemt–/– mice. Experiments in which mice were injected with Triton WR1339 showed that, whereas hepatic apoB100 secretion was decreased in male Pemt–/– mice, the decrease in plasma apoB48 in male Pemt–/– mice was not due to reduced secretion. Moreover, female and, to a lesser extent, male Pemt–/– mice showed a striking 40% decrease in plasma PC and cholesterol in high density lipoproteins. These results suggest that, even though the content of hepatic PC was normal in PEMT-deficient mice, plasma lipoprotein levels were profoundly altered in a gender-specific manner. Phosphatidylethanolamine N-methyltransferase (PEMT)is involved in a secondary pathway for production of phosphatidylcholine (PC) in liver. We fed Pemt–/–mice a high fat/high cholesterol diet for 3 weeks to determine whether or not PC derived from PEMT is required for very low density lipoprotein secretion. Lipid analyses of plasma and liver indicated that male Pemt–/– mice accumulated triacylglycerols in their livers and were unable to secrete the same amount of triacylglycerols from the liver as did Pemt+/+ mice. Plasma levels of triacylglycerol and both apolipoproteins B100 and B48 were significantly decreased only in male Pemt–/– mice. Experiments in which mice were injected with Triton WR1339 showed that, whereas hepatic apoB100 secretion was decreased in male Pemt–/– mice, the decrease in plasma apoB48 in male Pemt–/– mice was not due to reduced secretion. Moreover, female and, to a lesser extent, male Pemt–/– mice showed a striking 40% decrease in plasma PC and cholesterol in high density lipoproteins. These results suggest that, even though the content of hepatic PC was normal in PEMT-deficient mice, plasma lipoprotein levels were profoundly altered in a gender-specific manner. Phosphatidylcholine (PC) 1The abbreviations used are: PC, phosphatidylcholine; PE, phosphatidylethanolamine; apo, apolipoprotein; HDL, high density lipoprotein; HF/HC, high fat/high cholesterol; HPLC, high performance liquid chromatography; LPC, lysophosphatidylcholine; PEMT, phosphatidylethanolamine N-methyltransferase; PS, phosphatidylserine; SM, sphingomyelin; TG, triacylglycerols; VLDL, very low density lipoprotein. is synthesized by the Kennedy pathway (CDP-choline pathway), by methylation of phosphatidylethanolamine (PE), or by acylation of lyso-PC (LPC). The Kennedy pathway is the major route for phosphatidylcholine (PC) synthesis in all mammalian tissues and is dependent on the intake of choline (1Vance D.E. Vance D.E. Vance J.E. Biochemistry of Lipids, Lipoproteins, and Membranes. Elsevier, Amsterdam2002: 205-232Google Scholar). In the liver an additional pathway for PC production is catalyzed by phosphatidylethanolamine N-methyltransferase (PEMT), which converts PE to PC via the transfer of three methyl groups from S-adenosylmethionine (2Vance D.E. Ridgway N.D. Prog. Lipid Res. 1988; 22: 61-79Crossref Scopus (199) Google Scholar). The liver-specific expression of PEMT suggests that this enzyme might play a role in bile secretion and/or very low density lipoprotein (VLDL) secretion. PC is the primary phospholipid of all classes of lipoproteins in mammals (3Vance J.E. Vance D.E. Can. J. Biochem. Cell Biol. 1985; 63: 870-881Crossref PubMed Scopus (85) Google Scholar) and is required for the secretion of VLDL; other phospholipids cannot substitute (4Yao Z. Vance D.E. J. Biol. Chem. 1988; 263: 2998-3004Abstract Full Text PDF PubMed Google Scholar, 5Yao Z. Vance D.E. J. Biol. Chem. 1989; 264: 11373-11380Abstract Full Text PDF PubMed Google Scholar, 6Yao Z. Vance D.E. Biochem. Cell Biol. 1989; 68: 552-558Crossref Scopus (99) Google Scholar, 7Vermeulen P.S. Lingrell S. Yao Z. Vance D.E. J. Lipid Res. 1997; 38: 447-457Abstract Full Text PDF PubMed Google Scholar). The Kennedy pathway is required for maintaining normal plasma VLDL levels, because rats fed a choline-deficient diet for 3 days had a 6-fold increase in hepatic triacylglycerol (TG) and decreased plasma TG (6Yao Z. Vance D.E. Biochem. Cell Biol. 1989; 68: 552-558Crossref Scopus (99) Google Scholar). The role of PEMT-derived PC for lipoprotein secretion/metabolism has not been clearly established. Treatment of hepatocytes with 3-deazaadenosine, an inhibitor of methylation reactions that utilize S-adenosylmethionine, inhibited PEMT activity by more than 90% but did not decrease VLDL secretion (8Vance J.E. Nguyen T.M. Vance D.E. Biochim. Biophys. Acta. 1986; 875: 501-509Crossref PubMed Scopus (26) Google Scholar). Thus, PEMT activity did not appear to be required for VLDL secretion. Subsequent experiments revealed that one pool of hepatic PC, which was produced by the methylation of PE derived from phosphatidylserine (PS) decarboxylation, was preferentially incorporated into VLDL secreted by hepatocytes (9Vance J.E. Vance D.E. J. Biol. Chem. 1986; 261: 4486-4491Abstract Full Text PDF PubMed Google Scholar). Moreover, secretion of this pool of PC labeled by this pathway was not inhibited by 3-deazaadenosine even though this inhibitor reduced the incorporation of labeled serine into PC of hepatocytes by >90% (9Vance J.E. Vance D.E. J. Biol. Chem. 1986; 261: 4486-4491Abstract Full Text PDF PubMed Google Scholar, 10Vance J.E. Vance D.E. FEBS Let. 1986; 204: 243-246Crossref PubMed Scopus (18) Google Scholar). Because 3-deazaadenosine did not inhibit the incorporation of labeled serine into the headgroup of secreted PC, we cannot conclude that PEMT-derived PC is not important for VLDL secretion. More recent studies used bezafibrate to inhibit PEMT activity in rat hepatocytes (11Nishimaki-Mogami T. Suzuki K. Takjashi A. Biochim. Biophys. Acta. 1996; 1304: 12-31Google Scholar). The secretion of neither apo (apolipoprotein) B48 nor B100 was inhibited, but bezafibrate reduced the lipidation of apoB48 and thus caused a shift in the density of apoB48-containing lipoproteins in the media from that of VLDL to higher densities (11Nishimaki-Mogami T. Suzuki K. Takjashi A. Biochim. Biophys. Acta. 1996; 1304: 12-31Google Scholar). Neither bezafibrate nor 3-deazaadenosine are specific inhibitors of PEMT (8Vance J.E. Nguyen T.M. Vance D.E. Biochim. Biophys. Acta. 1986; 875: 501-509Crossref PubMed Scopus (26) Google Scholar, 11Nishimaki-Mogami T. Suzuki K. Takjashi A. Biochim. Biophys. Acta. 1996; 1304: 12-31Google Scholar). Thus, at this juncture the role for PEMT in VLDL secretion was not clear. A Pemt–/– mouse model now exists (12Walkey C.J. Donohue L.R. Bronson R. Agellon L.B. Vance D.E. Proc. Natl. Acad. S. A. 1997; PubMed Scopus Google Scholar). we more the role of PEMT in VLDL secretion. Pemt–/– mice appear normal fed a choline-deficient which liver 3 days C.J. Agellon L.B. Vance D.E. J. Biol. Chem. Full Text Full Text PDF PubMed Scopus Google Scholar). a in lipoprotein secretion was hepatocytes from male Pemt–/– mice were and the secretion of lipoproteins was with that from Pemt+/+ hepatocytes A. Vance D.E. J. Biol. Chem. Full Text Full Text PDF PubMed Scopus Google Scholar). These studies showed that a of PEMT in a decrease in secretion of apoB100 and a decrease in secretion of TG and PC with important to determine this decrease in VLDL secretion in Pemt–/– mice. The plasma lipoprotein and levels, as as VLDL in Pemt–/– mice as a of and but not Pemt–/– mice a in VLDL and apoB100 secretion with Pemt+/+ mice but only fed a high fat/high cholesterol In in Pemt–/– mice the of plasma cholesterol and PC in the high density lipoprotein was in and in than in their Pemt+/+ diet was from for of TG, and and were from for plasma phospholipids and cholesterol were from for were from PC, PE, PS, and were from and were from The was from and the was from the and the secondary to were from and the was from Triton and were from other and were from and of Pemt–/– and Pemt+/+ mouse had of and (12Walkey C.J. Donohue L.R. Bronson R. Agellon L.B. Vance D.E. Proc. Natl. Acad. S. A. 1997; PubMed Scopus Google Scholar) and were via in a the of weeks the were fed for 3 weeks or a high fat/high cholesterol diet Agellon L.B. J. Lipid Res. 1997; 38: Full Text PDF Google Scholar). The diet of of and cholesterol Agellon L.B. J. Lipid Res. 1997; 38: Full Text PDF Google Scholar). the the mice were in a 3 the were and and and tissues were and Lipid of livers were and with a in 3 of and by for was the from which is on the Biochem. PubMed Scopus Google Scholar). was used as a for all were from the liver by the of and Can. J. Biochem. PubMed Scopus Google Scholar). were by a of the the The were was and the were which to the of the of phospholipids the were by in a of were with and was with the J. Lipid Res. Full Text PDF PubMed Google Scholar). TG was by or the Biochim. Biophys. Acta. PubMed Scopus Google Scholar). cholesterol and were by Lipid of Plasma and was from mouse via the in the of of and plasma was by was to all plasma to a of cholesterol in both plasma and bile was the cholesterol to a cholesterol in plasma was with the in a in plasma was by the amount of cholesterol from the amount of Plasma TG was the The plasma from three to was and into lipoprotein high performance liquid with an to a or for cholesterol cholesterol and phospholipids were as C.J. Agellon L.B. Vance D.E. J. Biol. Chem. Full Text Full Text PDF PubMed Scopus Google Scholar). phospholipids were from of plasma or of bile from a Can. J. Biochem. PubMed Scopus Google Scholar) and by as The phospholipids were from the and J. Lipid Res. Full Text PDF PubMed Google Scholar). of Plasma and in plasma were as Biochem. Biophys. Scholar, Chem. PubMed Scopus Google Scholar) the and and of Plasma from to three was to a of to which was of to a density of was at the of a and to the with The were in a at for as J.E. K. 1986; PubMed Scopus Google Scholar, R. Vance D.E. Biochem. J. PubMed Scopus Google Scholar). with densities from to were of a of of was and for at D.E. Biochim. Biophys. Acta. PubMed Scopus Google Scholar). the was by for at and with The were in PubMed Scopus Google and were on a and was the were and for of the was by of in Pemt–/– and Pemt+/+ mice were and injected with of Triton and of as A. K. J. Lipid Res. Full Text Full Text PDF PubMed Google Scholar). the were and was in the of of plasma were of of Triton and and of and and all was at R. Vance D.E. Biochem. J. PubMed Scopus Google Scholar). was of with to and for at were by with and in R. Vance D.E. Biochem. J. PubMed Scopus Google Scholar, A. J. J. Lipid Res. 1996; Full Text PDF PubMed Google Scholar). were on and were with The were in and to were in and were by a with and In livers in were and with to of and of the of mice were fed an diet or a diet for 3 mice normal and The of male and female Pemt–/– mice were to of their A was in the of the liver as a of male Pemt–/– and Pemt+/+ mice fed an diet that of livers from male Pemt–/– mice fed the diet were in and were in an of with revealed in a in of the in the male Pemt–/– mice and did not with that were not with In livers of female Pemt–/– and Pemt+/+ mice were in showed that livers of female Pemt–/– mice but not a Because of in the livers of male Pemt–/– mice and plasma and were to the of liver the Pemt–/– mice on an diet only one male had levels of with for with for that the in plasma and hepatic were due to of PEMT activity than liver The Lipid of the by and in the levels of hepatic cholesterol were not by or PEMT the diet in the livers of all mice this increase in was more striking in the female mice of both of and in the livers of Pemt+/+ and on a and Pemt+/+ of the same and diet were on a and Pemt+/+ of the same and diet were on a and Pemt+/+ of the same and diet were in a The amount of TG in the livers on and of the in an increase of in the TG content of livers of male mice fed the In in female mice the liver TG content was of the hepatic TG results were to of mice fed the diet an of whereas a only in the male Pemt–/– mice. TG liver and Pemt–/– mice are fed a choline-deficient diet for 3 days C.J. Agellon L.B. Vance D.E. J. Biol. Chem. Full Text Full Text PDF PubMed Scopus Google Scholar). In mice, the content of PC in the liver was than in Pemt+/+ mice. Because the mice in the had been to phospholipid was to that the mice were not the of hepatic PC in female Pemt–/– mice on an diet was than in their Pemt+/+ of of is the normal of hepatic PC C.J. Agellon L.B. Vance D.E. J. Biol. Chem. Full Text Full Text PDF PubMed Scopus Google Scholar, Vance D.E. J. PubMed Scopus Google that the did not a choline-deficient of phospholipids in the livers of Pemt+/+ and on a and Pemt+/+ of the same and diet are on a and Pemt+/+ of the same and diet are in a Because PE is a for PEMT, one might that PE levels be in livers of with mice. that PE levels did not on or The of in the livers were because is synthesized by a from PC or PE (1Vance D.E. Vance D.E. Vance J.E. Biochemistry of Lipids, Lipoproteins, and Membranes. Elsevier, Amsterdam2002: 205-232Google Scholar). levels were by the of PEMT or diet were in major were male or female Pemt–/– and Pemt+/+ mice in the of bile in the not The in amount of PC in the bile of male and female Pemt–/– mice of of with Pemt+/+ mice of of was not secretion into bile is with PC secretion D.E. PubMed Scopus Google Scholar). The amount of cholesterol was not significantly Pemt+/+ and Pemt–/– mice of Plasma in in a phospholipids SM, and are the major phospholipids in mammalian plasma 1986; PubMed Scopus Google Scholar). Plasma PC in female Pemt–/– mice was 40% than in female Pemt+/+ mice The amount of plasma PC in male Pemt–/– mice on an diet was than in male Pemt+/+ mice Plasma levels were significantly decreased by in both male and female Pemt–/– mice, but levels were not significantly the of and PE did not for the in phospholipids in the plasma of Pemt–/– mice. is the higher of plasma PE in male with female mice of both phospholipids are altered in fed mice in a gender-specific on on on in a the gender-specific results on plasma cholesterol levels the results for plasma PC In Pemt–/– female mice fed the plasma cholesterol content was than in Pemt+/+ female mice The in plasma cholesterol content the of male mice was in Pemt–/– mice than in Pemt+/+ mice, In all the decrease in plasma cholesterol was due to a decrease in both and cholesterol not of the plasma of TG by PEMT was from that of PC and The plasma TG content of male mice was in Pemt–/– than in Pemt+/+ mice the amount of plasma TG was the same in female Pemt–/– and Pemt+/+ mice. These are with the of TG in the livers of but not Pemt–/– mice higher than Pemt+/+ Plasma was into lipoprotein by high performance liquid The content of cholesterol A and and phospholipids and in the of both male and female Pemt–/– mice was than in in with the of Because the cholesterol and phospholipid content of VLDL was to the of in experiments was not to the of PEMT on the content of in on the and lipoprotein of the in the Pemt–/– mice, is that PEMT-derived PC a role in the of in plasma lipoproteins in a gender-specific manner. Plasma in but an from to three was and of densities from to were by Lipid and in were and the were and by of and was The of apoB48 and apoB100 were decreased in the density lipoprotein of with male mice and but not in female mice A and The in apoB100 was more than in Because the of plasma TG is in VLDL, results are with the analyses of plasma TG In of the reduced content of cholesterol and phospholipids in the of female and male Pemt–/– mice A and we that might be a in the amount of in the plasma of Pemt–/– mice. as in and the of plasma was very in Pemt–/– and Pemt+/+ mice of both The that cholesterol be decreased an in the of has been K. Biol. PubMed Scopus Google Scholar). determine whether or not secretion was decreased in male Pemt–/– mice, we in of in the mice in the of Triton a that the of TG in plasma Pemt–/– and Pemt+/+ mice were injected with of Triton WR1339 and of The were and apoB100 and apoB48 were from The amount of apoB100 secreted was significantly in Pemt–/– mice with Pemt+/+ mice fed the diet A and in to the decreased apoB48 in the amount of apoB48 secreted was not significantly Pemt–/– and Pemt+/+ mice. Thus, the amount of plasma apoB48 in male Pemt–/– mice, with Pemt+/+ mice is the of than decreased secretion. of PEMT-derived PC in VLDL as a of results on mice fed the In Pemt–/– and Pemt+/+ mice fed a diet were of Pemt–/– mice fed the diet were not not in to the mice and the hepatic of TG in male Pemt–/– mice fed the diet did not the mice were fed Moreover, the plasma TG of male Pemt–/– mice was from that of the Pemt+/+ and for Pemt–/– and Pemt+/+ mice, The secretion of neither apoB100 nor apoB48 was by the PEMT in mice fed the diet results clearly that PEMT-derived PC an important role in VLDL this only male mice are with an of PEMT-derived PC for Plasma as a of female Pemt–/– mice fed the plasma PC levels were than in their Pemt+/+ the diet for plasma cholesterol in female mice for plasma Thus, the of PEMT-derived PC for plasma PC and cholesterol in female mice is of the female mice, Pemt–/– male mice had normal plasma PC and cholesterol with Pemt+/+ A and The diet plasma PC and cholesterol in Pemt+/+ mice but not in PEMT-deficient mice. These were in the in plasma not Thus, in male mice the role of PEMT-derived PC on plasma PC and cholesterol was dependent on the of the The results in this that PEMT is required for normal secretion of VLDL PC, and in male mice with an These are with in hepatocytes derived from male Pemt–/– and Pemt+/+ mice in which the secretion of TG, PC, and apoB100 into VLDL was decreased by the hepatocytes were with A. Vance D.E. J. Biol. Chem. Full Text Full Text PDF PubMed Scopus Google Scholar). additional and is that in Pemt–/– mice, cholesterol and PC were reduced in and in with Pemt+/+ mice. These in which PC lipoprotein in mice and the are in lipoprotein a of PEMT the amount of cholesterol and PC in plasma a of PEMT VLDL are in lipoprotein dependent the route of PC PC is required for at of VLDL secretion. PC is the major on the of the VLDL PC is the major phospholipid of the of the pathway and plasma Thus, a of PC in the pathway or in the might the secretion of Because the secretion of in PEMT-deficient mice, that the secretion pathway is the of VLDL secretion in the Pemt–/– male mice is due to a in the PC content of the of the VLDL in in PEMT-deficient that of PC in the liver is via PEMT R. J. Biol. Chem. Full Text PDF PubMed Google Scholar, C.J. Z. J. Biol. Chem. Full Text Full Text PDF PubMed Scopus Google Scholar, Biochim. Biophys. Acta. PubMed Scopus Google Scholar). In female rats a of PC in the liver is from PE methylation than in male rats J. J. Lipid Res. Full Text PDF PubMed Google Scholar, R. Biochem. PubMed Scopus Google Scholar, A. S. PubMed Scopus Google Scholar, J. Google Scholar). has that the same is in mice. A. and the that VLDL secretion is inhibited in but not Pemt–/– mice. for female Pemt–/– mice not a in VLDL secretion is that female mice might an for the hepatic of PC from In of this female Pemt–/– mice a decrease in that was of diet In the hepatic of PC from is a important because phospholipids to of PC T. J. 264: PubMed Google Scholar). this were the in mice, PEMT might in an of with a in the amount of PC and cholesterol in the plasma of Pemt–/– mice as the female Pemt–/– mice might PC from to a normal of VLDL even with a high The of cholesterol from to for is to the of PC S. Biochim. Biophys. Acta. PubMed Scopus Google Scholar). Thus, for the in plasma PC in PEMT-deficient mice might be that mice to a of PEMT by PC for plasma In a were the levels of PC, in plasma of rats in which the pathway was by a choline-deficient diet (6Yao Z. Vance D.E. Biochem. Cell Biol. 1989; 68: 552-558Crossref Scopus (99) Google Scholar). in experiments only male rats were PEMT-derived PC is required for an in which the pathway is inhibited in female mice might the amount of PC in or not the is only in mice and not rats cannot be due to a of a rat results the of PC in plasma from liver. is that are to due to low plasma J. PubMed Scopus Google Scholar). The of this in is not the we in this in the of VLDL secretion the might to a of this The of in VLDL secretion in male Pemt–/– mice was only with the of an VLDL secretion was in male Pemt–/– mice fed a as as in fed Thus, in the of PEMT-derived PC did not VLDL secretion. The PC pathway in liver is the Kennedy pathway (1Vance D.E. Vance D.E. Vance J.E. Biochemistry of Lipids, Lipoproteins, and Membranes. Elsevier, Amsterdam2002: 205-232Google and has that is in the livers of all Pemt–/– mice (12Walkey C.J. Donohue L.R. Bronson R. Agellon L.B. Vance D.E. Proc. Natl. Acad. S. A. 1997; PubMed Scopus Google Scholar). the of plasma PC and are other by which the livers of mice might for the of PEMT-derived the of Pemt–/– mice to normal VLDL secretion been a of and of PC In the male Pemt–/– mice fed the PC levels or the of PC has for the and/or secretion of The results that PEMT-derived PC the for PC in to specific as an plasma as a of a high is a for the of in J. PubMed Scopus Google Scholar). Thus, that the of PEMT-derived PC VLDL secretion in to an diet to a of the liver to in and PEMT and VLDL major phospholipid in VLDL, PC, is into the of VLDL has that, the pathway is in male rats by a choline the of PC, and TG in plasma VLDL are decreased by (6Yao Z. Vance D.E. Biochem. Cell Biol. 1989; 68: 552-558Crossref Scopus (99) Google Scholar). We in VLDL to a in PC synthesis from and a in the amount of PC in the liver. We now the PEMT pathway for PC synthesis in mice and a in VLDL secretion in male mice with an in Pemt–/– mice the secretion of only but not was the pathway was inhibited in the plasma levels of both apoB48 and apoB100 were reduced (6Yao Z. Vance D.E. Biochem. Cell Biol. 1989; 68: 552-558Crossref Scopus (99) Google Scholar). These are with experiments from that TG, or TG transfer is the secretion of apoB100 is inhibited to a than that of apoB48 J. S. J. Biol. Chem. Full Text PDF PubMed Google Scholar, J. J. Biol. Chem. Full Text Full Text PDF PubMed Scopus Google Scholar, A. S. Vance J.E. J. Biol. Chem. Full Text Full Text PDF PubMed Scopus Google Scholar). for the of apoB100 and apoB48 secretion on PC is that a in PC synthesis by the PEMT or the secretion of apoB48 secretion not the PEMT pathway but PC by the In not the that a of PC at a specific in the livers of Pemt–/– mice is for the reduced secretion of VLDL even though the of PC in the liver is not significantly because the in Pemt–/– mice is only in and the one that we is that secretion of both apoB48 and apoB100 into VLDL by the liver is inhibited PC in the liver a as a of a of PC by The of PC in the liver of rats was significantly reduced were fed a choline-deficient diet for 3 days (6Yao Z. Vance D.E. Biochem. Cell Biol. 1989; 68: 552-558Crossref Scopus (99) Google whereas the amount of PC in the livers of Pemt–/– mice was not significantly reduced the PEMT pathway was has that the pathway for PC synthesis is in livers of Pemt–/– mice (12Walkey C.J. Donohue L.R. Bronson R. Agellon L.B. Vance D.E. Proc. Natl. Acad. S. A. 1997; PubMed Scopus Google as for the of PC from Thus, the in PC in PEMT-deficient mice is not as as in rats fed the choline-deficient diet for 3 by which Pemt–/– mice might for the decrease in PC synthesis is by the of PC and/or lyso-PC from plasma and/or by PC C.J. J. Biol. Chem. Full Text PDF PubMed Google Scholar). We that VLDL more PC is required to the apoB100 in the of the pathway than for the Thus, apoB100 might be more than apoB48 to reduced hepatic PC apoB100 be in both choline-deficient and PEMT-deficient whereas apoB48 secretion be inhibited only the PC content of the liver was more as the pathway was Moreover, one that, the mice were fed an than the for PC be to the secretion of VLDL and for of PC in PEMT is a liver-specific enzyme (2Vance D.E. Ridgway N.D. Prog. Lipid Res. 1988; 22: 61-79Crossref Scopus (199) Google we that PEMT-derived PC might be required for liver-specific VLDL and bile secretion. The experiments in this the of PC for lipoprotein and bile secretion in phospholipid is Vance D.E. Vance J.E. Biochemistry of Lipids, Lipoproteins, and Membranes. Elsevier, Scholar, Vance D.E. Biochem. J. PubMed Scopus Google a that is by that PC synthesis from is in to of PEMT activity (12Walkey C.J. Donohue L.R. Bronson R. Agellon L.B. Vance D.E. Proc. Natl. Acad. S. A. 1997; PubMed Scopus Google Scholar). that a of PC for maintaining be more important than PC for lipoprotein secretion. is not in male Pemt–/– mice the of PC is used to a normal secretion of PC into whereas the secretion of TG in VLDL is of normal bile secretion is on the PC pool in the liver. has been that in mice an amount of PC to the of PC in liver is secreted into bile C.J. Agellon L.B. Vance D.E. J. Biol. Chem. Full Text Full Text PDF PubMed Scopus Google Scholar, Biochem. 1997; PubMed Scopus (26) Google Scholar). is required for the normal and of an important of for the the other hepatic VLDL secretion is a by which liver for of other are with the that an intake of an from the in a is more important to the mouse than lipoprotein secretion by the liver. We Pemt–/– mice to determine the of PEMT-derived PC in the liver. Because phospholipid is and more than one pathway exists for production of all the major phospholipids PC J.E. Biochem. Full Text Full Text PDF PubMed Scopus Google is to the of the PEMT The suggests that PEMT activity an important role in the levels of plasma lipoproteins. major is that in male mice PEMT-derived PC the for PC in to a as an the of PC for VLDL secretion cannot be in Pemt–/– mice by the pathway or not the PEMT pathway a pool of PC for VLDL is an that to be the levels of plasma cholesterol and PC in are in mice by PEMT activity in liver.

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