Intestinal de novo phosphatidylcholine synthesis is required for dietary lipid absorption and metabolic homeostasis

De novo phosphatidylcholine (PC) synthesis via CTP:phosphocholine cytidylyltransferase-α (CTα) is required for VLDL secretion. To determine the precise role of de novo PC synthesis in intestinal lipid metabolism, we deleted CTα exclusively in the intestinal epithelium of mice (CTαIKO mice). When fed a chow diet, CTαIKO mice showed normal fat absorption despite a ∼30% decrease in intestinal PC concentrations relative to control mice, suggesting that biliary PC can fully support chylomicron secretion under these conditions. However, when fed a high-fat diet, CTαIKO mice showed impaired passage of FAs and cholesterol from the intestinal lumen into enterocytes. Impaired intestinal lipid uptake in CTαIKO mice was associated with lower plasma triglyceride concentrations, higher plasma glucagon-like peptide 1 and peptide YY, and disruption of intestinal membrane lipid transporters after a high-fat meal relative to control mice. Unexpectedly, biliary bile acid and PC secretion was enhanced in CTαIKO mice due to a shift in expression of bile-acid transporters to the proximal intestine, indicative of accelerated enterohepatic cycling. These data show that intestinal de novo PC synthesis is required for dietary lipid absorption during high-fat feeding and that the reacylation of biliary lyso-PC cannot compensate for loss of CTα under these conditions. De novo phosphatidylcholine (PC) synthesis via CTP:phosphocholine cytidylyltransferase-α (CTα) is required for VLDL secretion. To determine the precise role of de novo PC synthesis in intestinal lipid metabolism, we deleted CTα exclusively in the intestinal epithelium of mice (CTαIKO mice). When fed a chow diet, CTαIKO mice showed normal fat absorption despite a ∼30% decrease in intestinal PC concentrations relative to control mice, suggesting that biliary PC can fully support chylomicron secretion under these conditions. However, when fed a high-fat diet, CTαIKO mice showed impaired passage of FAs and cholesterol from the intestinal lumen into enterocytes. Impaired intestinal lipid uptake in CTαIKO mice was associated with lower plasma triglyceride concentrations, higher plasma glucagon-like peptide 1 and peptide YY, and disruption of intestinal membrane lipid transporters after a high-fat meal relative to control mice. Unexpectedly, biliary bile acid and PC secretion was enhanced in CTαIKO mice due to a shift in expression of bile-acid transporters to the proximal intestine, indicative of accelerated enterohepatic cycling. These data show that intestinal de novo PC synthesis is required for dietary lipid absorption during high-fat feeding and that the reacylation of biliary lyso-PC cannot compensate for loss of CTα under these conditions. Phospholipids form the matrix of biological membranes, provide precursors for a variety of signaling molecules, and allow assembly and secretion of lipoproteins (1.van der Veen J.N. Kennelly J.P. Wan S. Vance J.E. Vance D.E. Jacobs R.L. The critical role of phosphatidylcholine and phosphatidylethanolamine metabolism in health and disease.Biochim. Biophys. Acta. 2017; 1859: 1558-1572Crossref PubMed Scopus (535) Google Scholar). Phosphatidylcholine (PC) is the primary phospholipid in eukaryotic cells (1.van der Veen J.N. Kennelly J.P. Wan S. Vance J.E. Vance D.E. Jacobs R.L. The critical role of phosphatidylcholine and phosphatidylethanolamine metabolism in health and disease.Biochim. Biophys. Acta. 2017; 1859: 1558-1572Crossref PubMed Scopus (535) Google Scholar). The amphitropic enzyme CTP:phosphocholine cytidylyltransferase (CT) regulates de novo PC synthesis in response to changes in membrane lipid composition in all nucleated mammalian cells (2.Cornell R.B. Ridgway N.D. CTP:phosphocholine cytidylyltransferase: Function, regulation, and structure of an amphitropic enzyme required for membrane biogenesis.Prog. Lipid Res. 2015; 59: 147-171Crossref PubMed Scopus (78) Google Scholar). Global deletion of CTα (encoded by Pcyt1a) is embryonic lethal in mice, reflecting the essential role of membrane biogenesis during development (3.Wang L. Magdaleno S. Tabas I. Jackowski S. Early embryonic lethality in mice with targeted deletion of the CTP:phosphocholine cytidylyltransferase alpha gene (Pcyt1a).Mol. Cell. Biol. 2005; 25: 3357-3363Crossref PubMed Scopus (87) Google Scholar). Mice lacking CTα in the liver have impaired VLDL secretion and accumulate neutral lipids in hepatocytes (4.Jacobs R.L. Devlin C. Tabas I. Vance D.E. Targeted deletion of hepatic CTP:phosphocholine cytidylyltransferase alpha in mice decreases plasma high density and very low density lipoproteins.J. Biol. Chem. 2004; 279: 47402-47410Abstract Full Text Full Text PDF PubMed Scopus (137) Google Scholar), despite the presence of a second route for hepatic PC synthesis via the methylation of phosphatidylethanolamine (PE) by phosphatidylethanolamine-N-methyltransferase (PEMT). Similarly, CTα cannot compensate for the loss of PEMT in generating PC for VLDL assembly (5.Noga A.A. Zhao Y. Vance D.E. An unexpected requirement for phosphatidylethanolamine N-methyltransferase in the secretion of very low density lipoproteins.J. Biol. Chem. 2002; 277: 42358-42365Abstract Full Text Full Text PDF PubMed Scopus (183) Google Scholar). Intestinal PC can be derived from the diet, bile, circulating lipoproteins, and local de novo synthesis. Dietary and biliary PC is hydrolyzed in the intestinal lumen by phospholipase A2 to lyso-PC and FAs before being absorbed into enterocytes, delivered to the endoplasmic reticulum, and reacylated into PC by lyso-PC acyltransferase enzymes (6.Nilsson A. Intestinal absorption of lecithin and lysolecithin by lymph fistula rats.Biochim. Biophys. Acta. 1968; 152: 379-390Crossref PubMed Scopus (76) Google Scholar, 7.Parthasarathy S. Subbaiah P.V. Ganguly J. The mechanism of intestinal absorption of phosphatidylcholine in rats.Biochem. J. 1974; 140: 503-508Crossref PubMed Scopus (54) Google Scholar). Mice lacking hepatic Abcb4, which is required for PC secretion into bile, have normal passage of FAs from the intestinal lumen into enterocytes but have impaired chylomicron assembly and secretion, highlighting the importance of biliary PC for chylomicron output (8.Voshol P.J. Minich D.M. Havinga R. Elferink R.P. Verkade H.J. Groen A.K. Kuipers F. Postprandial chylomicron formation and fat absorption in multidrug resistance gene 2 P-glycoprotein-deficient mice.Gastroenterology. 2000; 118: 173-182Abstract Full Text Full Text PDF PubMed Scopus (51) Google Scholar). Furthermore, loss of intestinal lysophosphatidylcholine acyltransferase 3 (Lpcat3), which incorporates PUFAs into PC, impairs dietary lipid absorption despite maintenance of total intestinal PC mass (9.Li Z. Jiang H. Ding T. Lou C. Bui H.H. Kuo M.S. Jiang X.C. Deficiency in lysophosphatidylcholine acyltransferase 3 reduces plasma levels of lipids by reducing lipid absorption in mice.Gastroenterology. 2015; 149: 1519-1529Abstract Full Text Full Text PDF PubMed Scopus (54) Google Scholar, 10.Wang B. Rong X. Duerr M.A. Hermanson D.J. Hedde P.N. Wong J.S. Vallim T.Q. Cravatt B.F. Gratton E. Ford D.A. phospholipid is required for uptake and a high-fat Full Text Full Text PDF PubMed Scopus Google Scholar). the of PC to the intestinal lumen chylomicron secretion H. of biliary phosphatidylcholine in the absorption and of dietary in the Full Text PDF PubMed Scopus Google Scholar). the reacylation of lyso-PC derived from the intestinal lumen is for chylomicron the precise that intestinal de novo PC synthesis to is the we that loss of intestinal CTα triglyceride in enterocytes due to of PC for chylomicron However, we that loss of intestinal de novo PC synthesis impairs passage of FAs from the intestinal lumen into enterocytes in the of a high-fat but a chow is to the of in enhanced secretion, and Furthermore, we show that loss of intestinal CTα biliary bile acid and lipid secretion by enterohepatic bile acid cycling. data provide of a requirement for intestinal de novo PC synthesis in the maintenance of intestinal and show that the reacylation of lyso-PC from is to during Mice a a with mice a under the control of a F. L. S. and in the 2004; PubMed Scopus Google to mice the to a deletion of intestinal CTα after of mice in the of mice the to a deletion of intestinal CTα after was from with a and a a was in mice by of in for mice Mice fed a chow a fat Mice in a with and to and after a after by 2 with and The was into of to before in for cells in after The of all which in with of the with and with a 2 with and in with an with an and a was from intestinal liver was was an for a in expression was to was the in Intestinal absorption was C. J. Wong J.S. B. S. 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Intestinal concentrations a The relative of PC in cells was by mass The of To the composition of intestinal PC, lipids from intestinal and by PC from the and to by with 2 of and of in for 1 by the of total FAs Intestinal cholesterol and cholesterol by with after with and of with the A. of plasma total lipid by Biophys. PubMed Scopus Google Scholar). and to a before of lipids by the of J. for the and of total from Biol. Chem. Full Text PDF PubMed Google Scholar). and cholesterol concentrations in of mice with Intestinal CTα was by the of into (4.Jacobs R.L. Devlin C. Tabas I. Vance D.E. Targeted deletion of hepatic CTP:phosphocholine cytidylyltransferase alpha in mice decreases plasma high density and very low density lipoproteins.J. Biol. Chem. 2004; 279: 47402-47410Abstract Full Text Full Text PDF PubMed Scopus (137) Google Scholar). was from the with a after a after 2 after 2 by an of was by in and before being for to glucagon-like peptide 1 peptide and by to the was a for and for to a to a membrane and with and with and with a was was to was when with with was to determine the of and an of with in mice to CTαIKO and CTα enzyme in the and by with control mice and in the of CTαIKO mice for of mice with a deletion of intestinal CTα fed a chow a in plasma fat absorption after an lipid despite a decrease in intestinal with control mice of intestinal CTα of the mice fed the chow diet, and mass of CTαIKO mice was to that of after Furthermore, of after in CTαIKO with control that intestinal CTα is required for maintenance of in mice. PC concentrations lower in the and of CTαIKO mice with after an Furthermore, concentrations higher in the of CTαIKO mice in a decrease in the of in the of CTαIKO mice plasma cholesterol concentrations lower in CTαIKO mice fed the chow diet, plasma and concentrations with control mice. Unexpectedly, despite the of intestinal CTα and a decrease in the of intestinal membranes, in plasma was CTαIKO mice and control mice after an of in to the liver PC synthesis is required for VLDL secretion (4.Jacobs R.L. Devlin C. Tabas I. Vance D.E. Targeted deletion of hepatic CTP:phosphocholine cytidylyltransferase alpha in mice decreases plasma high density and very low density lipoproteins.J. Biol. Chem. 2004; 279: 47402-47410Abstract Full Text Full Text PDF PubMed Scopus (137) Google Scholar), intestinal de novo PC synthesis is for chylomicron secretion in the of a These that PC to the in bile is for chylomicron formation and secretion under these conditions. that feeding mice a for lipid and chylomicron PC and changes to the intestinal epithelium of CTαIKO mice. of showed that of CTαIKO mice of and and of the of these mice under the of CTαIKO mice but fat lower plasma concentrations, and lower liver concentrations control mice of the loss in CTαIKO mice with by control mice with by CTαIKO mice and after of the The CTαIKO mice fed a for and fat mass with The lower in CTαIKO mice with control mice in the of the to be an response to the diet, was CTαIKO mice and control mice by for control mice with for CTαIKO was lower in CTαIKO mice to CTα mice (4.Jacobs R.L. Devlin C. Tabas I. Vance D.E. Targeted deletion of hepatic CTP:phosphocholine cytidylyltransferase alpha in mice decreases plasma high density and very low density lipoproteins.J. Biol. Chem. 2004; 279: 47402-47410Abstract Full Text Full Text PDF PubMed Scopus (137) Google Scholar), plasma and cholesterol concentrations in CTαIKO mice after being fed a for these data show that feeding feeding reduces in CTαIKO mice. To determine impaired dietary lipid absorption to the loss in CTαIKO mice fed the we plasma lipid and CTαIKO mice 3 of the to of before for 2 was CTαIKO and control mice during concentrations lower and plasma concentrations lower in CTαIKO mice with after 2 Furthermore, CTαIKO mice in the with despite a in plasma concentrations after plasma concentrations that of the was impaired in CTαIKO mice, the of was plasma cholesterol concentrations CTαIKO and control mice after However, CTαIKO mice cholesterol in the cholesterol and plasma concentrations To determine enhanced to the low plasma in CTαIKO mice, we the mice with an of after of an of Intestinal secretion in CTαIKO mice the plasma after was in CTαIKO mice with fed a for in control mice with in CTαIKO these data show that the in the of de novo PC synthesis. that impaired intestinal secretion in CTαIKO mice was due to in enterocytes. However, CTαIKO mice lower concentrations control mice after and To the of uptake in the intestine, we mice with The in the of CTαIKO mice, absorption is was lower in control mice the of in plasma was in CTαIKO mice these data that loss of intestinal CTα impairs uptake from the intestinal lumen into enterocytes in the of a of 2 after a of lipid in enterocytes of CTαIKO mice with control mice fed the lipid in enterocytes of CTαIKO mice with FAs showed a of lipid in CTαIKO enterocytes 2 after an with lower concentrations in enterocytes, the levels of 2 2 and lower in CTαIKO 2 after a meal These data that of intestinal PC synthesis reduces uptake from the intestinal lumen and for lipid and chylomicron support of impaired fat in of CTαIKO mice with control mice concentrations higher in of CTαIKO mice with control mice To cholesterol control and CTαIKO mice an of and an of and the in plasma and the of in the of CTαIKO mice was lower in control mice Furthermore, of was higher in CTαIKO mice These data that cholesterol absorption is impaired with loss of intestinal The of of from plasma after of and in neutral was suggesting that hepatic cholesterol uptake was by loss of intestinal Furthermore, was in of in bile suggesting that hepatic bile acid synthesis was in response to intestinal cholesterol absorption in CTαIKO mice impaired cholesterol cholesterol and cholesterol concentrations in CTαIKO mice relative to of to cholesterol and in the of CTαIKO mice relative to of intestinal cholesterol in CTαIKO mice be a response to impaired cholesterol be due to intestinal phospholipid in B. Rong X. J. Ford D.A. and cholesterol intestinal and Cell. Full Text Full Text PDF PubMed Scopus Google Scholar). and structure suggesting that lipid in CTαIKO mice is due to to the intestinal epithelium Intestinal deletion in mice reduces lipid into enterocytes by reducing the of PUFAs into intestinal PC (9.Li Z. Jiang H. Ding T. Lou C. Bui H.H. Kuo M.S. Jiang X.C. Deficiency in lysophosphatidylcholine acyltransferase 3 reduces plasma levels of lipids by reducing lipid absorption in mice.Gastroenterology. 2015; 149: 1519-1529Abstract Full Text Full Text PDF PubMed Scopus (54) Google Scholar, 10.Wang B. Rong X. Duerr M.A. Hermanson D.J. Hedde P.N. Wong J.S. Vallim T.Q. Cravatt B.F. Gratton E. Ford D.A. phospholipid is required for uptake and a high-fat Full Text Full Text PDF PubMed Scopus Google Scholar). The levels of in CTαIKO mice relative to PC concentrations lower in CTαIKO mice the concentrations with However, the relative of PC by mass was with in the relative of PC and PC in CTαIKO mice To mass we of the of PC and that the composition of FAs to PC in the proximal was impaired lipid absorption in CTαIKO mice is due to changes in the relative of PC in mice in intestinal However, an of intestinal lipid into enterocytes of CTαIKO mice. The membrane lipid transporters acid and cholesterol 1 lipid absorption in intestinal cells F. impairs intestinal lipid secretion and of from the 2005; PubMed Scopus Google Scholar, A. D.J. S. S. A. of the intestinal acid Cell. Full Text Full Text PDF PubMed Scopus Google Scholar, X. A. 1 is critical for intestinal cholesterol 2004; PubMed Scopus Google Scholar). The levels of lower in CTαIKO mice relative to control mice Furthermore, and levels lower in CTαIKO mice expression of membrane transporters in intestinal lipid uptake relative to for impaired lipid absorption in CTαIKO mice. Dietary FAs in the lumen of the secretion of and from cells to control and D.E. J. of PubMed Scopus Google Scholar). CTαIKO mice have impaired absorption in the proximal in of we that the higher of FAs in the of CTαIKO mice and secretion. CTαIKO mice and in plasma 2 after the of is to secretion from the D.E. J. of PubMed Scopus Google Scholar). CTαIKO mice a higher plasma concentrations with is a with and lipid metabolism and is to changes in E. the of PubMed Scopus Google Scholar, J.S. E. is by and is a of hepatic lipid metabolism in Full Text Full Text PDF PubMed Scopus Google Scholar, A. A. Ford R. J.S. a 2005; PubMed Scopus Google Scholar). concentrations of higher in CTαIKO mice with after To the changes to circulating concentrations metabolism, we mice a for 2 before with an CTαIKO mice lower concentrations with after the plasma and and mice with a deletion of intestinal CTα These data impaired lipid uptake in the of intestinal CTα to enhanced and hepatic secretion, to in CTαIKO mice relative to control mice. that CTαIKO mice can and intestinal in the of de novo PC synthesis. we that biliary PC secretion to the maintenance of intestinal PC concentrations and intestinal in CTαIKO mice. To biliary lipid and bile acid secretion, we the of mice fed the The of bile in CTαIKO mice was higher in control mice with a of biliary bile acid secretion, a in phospholipid secretion, and a in cholesterol secretion with biliary lyso-PC to the intestinal the levels of lysophosphatidylcholine acyltransferase which the of acid to lyso-PC H. S. H. R. T. of a acyltransferase essential for membrane and PubMed Scopus Google Scholar), was higher in CTαIKO mice 2 after a higher of of biliary PC to the of CTαIKO mice to to intestinal in the of de novo intestinal PC synthesis. total biliary bile acid concentrations higher in CTαIKO mice, the bile acid composition was for which was the bile acid was control and CTαIKO mice a higher plasma bile acid concentrations in CTαIKO mice fed the was was in the hepatic expression of in bile acid and total bile acid concentrations CTαIKO mice and control mice fed the These data that enhanced biliary bile acid and lipid secretion in CTαIKO mice is by an in hepatic bile acid synthesis. was a in levels of the acid 2 to the under normal in the of CTαIKO mice An in is to bile acid absorption in the proximal and to enterohepatic of bile C. T. de S. Havinga R. H. R. intestinal bile acid via 2015; Full Text Full Text PDF PubMed Scopus (78) Google Scholar). with bile acid uptake in the proximal intestine, levels of the bile-acid acid a an in the of CTαIKO mice with 2 after Furthermore, and levels alpha lower in CTαIKO mice in from control mice. loss of intestinal CTα the secretion of bile and lipids from the liver by a mechanism that a shift in of bile to the proximal to enterohepatic cycling. we show that intestinal PC synthesis via CTα a role in the response of mice to data that the response to a in CTαIKO mice is by a of impaired dietary lipid secretion of the and and Furthermore, a shift in expression of bile to the proximal of CTαIKO mice is to accelerated enterohepatic bile acid cycling. of intestinal CTα is by mice fed a that de novo PC synthesis is required for normal intestinal Furthermore, data show that reacylation of lyso-PC from the intestinal lumen cannot compensate for loss of PC in enterocytes. Mice with intestinal deletion of the gene the PC enzyme have chylomicron secretion when fed a chow due to to PUFAs into intestinal PC, which membrane and uptake (9.Li Z. Jiang H. Ding T. Lou C. Bui H.H. Kuo M.S. Jiang X.C. Deficiency in lysophosphatidylcholine acyltransferase 3 reduces plasma levels of lipids by reducing lipid absorption in mice.Gastroenterology. 2015; 149: 1519-1529Abstract Full Text Full Text PDF PubMed Scopus (54) Google Scholar, 10.Wang B. Rong X. Duerr M.A. Hermanson D.J. Hedde P.N. Wong J.S. Vallim T.Q. Cravatt B.F. Gratton E. Ford D.A. phospholipid is required for uptake and a high-fat Full Text Full Text PDF PubMed Scopus Google Scholar). we that de novo PC synthesis is required for chylomicron secretion in the of a that the reacylation of lyso-PC derived from bile can fully chylomicron assembly under these conditions. However, an in concentrations for PC to membrane lipid and the for lipid and lipoproteins (2.Cornell R.B. Ridgway N.D. CTP:phosphocholine cytidylyltransferase: Function, regulation, and structure of an amphitropic enzyme required for membrane biogenesis.Prog. Lipid Res. 2015; 59: 147-171Crossref PubMed Scopus (78) Google Scholar). CTαIKO mice have intestinal due to of FAs into intestinal which PC impaired dietary lipid uptake changes to the relative of PC expression in the for intestinal PC formation de novo PC synthesis and PC required for dietary lipid absorption when a Furthermore, mice changes in bile acid concentrations B. Rong X. Duerr M.A. Hermanson D.J. Hedde P.N. Wong J.S. Vallim T.Q. Cravatt B.F. Gratton E. Ford D.A. phospholipid is required for uptake and a high-fat Full Text Full Text PDF PubMed Scopus Google Scholar), suggesting that the of de novo PC synthesis and PC control of enterohepatic a to that CTαIKO mice fed a have impaired in the of with lower Impaired lipid uptake in mice lacking intestinal de novo PC synthesis is due to to the intestinal an loss of intestinal CTα is to intestinal in the of a expression of in dietary lipid Targeted deletion of C. J. Wong J.S. B. S. Deficiency of the intestinal enzyme mice from by high-fat PubMed Scopus Google Scholar), F. impairs intestinal lipid secretion and of from the 2005; PubMed Scopus Google Scholar), F. Y. H. F. B. H. J. L. Intestinal reduces lipid PubMed Scopus Google Scholar), and X. A. 1 is critical for intestinal cholesterol 2004; PubMed Scopus Google Scholar), all of which lower in the of CTαIKO mice relative to impairs dietary lipid intestinal de novo PC synthesis a of in dietary lipid The intestinal epithelium is in and that that PC (2.Cornell R.B. Ridgway N.D. CTP:phosphocholine cytidylyltransferase: Function, regulation, and structure of an amphitropic enzyme required for membrane biogenesis.Prog. Lipid Res. 2015; 59: 147-171Crossref PubMed Scopus (78) Google Scholar). we that CTαIKO mice can and intestinal in the of de novo intestinal PC synthesis. biliary PC secretion to the maintenance of intestinal PC concentrations in CTαIKO mice. that deletion of intestinal CTα the of biliary bile acid secretion in CTαIKO mice with control mice. bile bile biliary cholesterol and phospholipid secretion, these higher in CTαIKO mice H.J. Kuipers F. into the mechanism of bile biliary lipid Google Scholar). The higher of of bile composition to bile in into the intestinal lumen of CTαIKO mice that impaired absorption with loss of intestinal CTα is due to a of required for fat Furthermore, the the of bile and of the expression of bile that hepatic bile acid synthesis is by loss of intestinal enterohepatic of bile is is by a shift in expression of and proximal of the shift in the expression of bile to the proximal in mice lacking intestinal a that T. E. S. is essential for the maintenance of in the Cell. Biol. PubMed Scopus Google Scholar, M.A. M.A. is essential for in mice.Gastroenterology. Full Text Full Text PDF PubMed Scopus Google Scholar). The in expression of bile in intestinal mice is to impaired lipid absorption M.A. M.A. is essential for in mice.Gastroenterology. Full Text Full Text PDF PubMed Scopus Google and bile C. T. de S. Havinga R. H. R. intestinal bile acid via 2015; Full Text Full Text PDF PubMed Scopus (78) Google Scholar). the that the and liver in bile formation in CTαIKO mice to enterohepatic of bile can and metabolism B. A. S. and in Biol. Chem. Full Text Full Text PDF PubMed Scopus Google Scholar). Furthermore, bile the circulating of X. Y. of the hepatic expression and secretion of Biol. Chem. Full Text Full Text PDF PubMed Scopus Google Scholar), a that is in CTαIKO mice and that reduces when E. the of PubMed Scopus Google Scholar). changes in bile acid metabolism to in the CTαIKO mice fed a and that can the and after secretion from cells D.E. J. of PubMed Scopus Google Scholar). normal dietary FAs absorbed in the proximal However, high concentrations of FAs cells of the intestine, can and secretion D.E. J. of PubMed Scopus Google Scholar). mice with intestinal deletion of in dietary fat C. J. Wong J.S. B. S. Deficiency of the intestinal enzyme mice from by high-fat PubMed Scopus Google Scholar), 1 S. A. S. S. reduces triglyceride and by chylomicron secretion and Lipid Res. Full Text Full Text PDF PubMed Scopus (51) Google Scholar), and B. Rong X. Duerr M.A. Hermanson D.J. Hedde P.N. Wong J.S. Vallim T.Q. Cravatt B.F. Gratton E. Ford D.A. phospholipid is required for uptake and a high-fat Full Text Full Text PDF PubMed Scopus Google Scholar), have high plasma Similarly, impaired absorption in the proximal of CTαIKO mice FAs to the to secretion. The of and secretion by FAs in CTαIKO mice to response to a with a chow diet, was in mice B. Rong X. Duerr M.A. Hermanson D.J. Hedde P.N. Wong J.S. Vallim T.Q. Cravatt B.F. Gratton E. Ford D.A. phospholipid is required for uptake and a high-fat Full Text Full Text PDF PubMed Scopus Google Scholar). plasma is associated with secretion and lower concentrations in CTαIKO mice with control mice fed a Furthermore, enhanced secretion for the lower concentrations in CTαIKO mice with by in enhanced secretion in CTαIKO mice to by with that control E. of circulating in PubMed Scopus Google Scholar). that of intestinal phospholipid metabolism can by the secretion of that intestinal de novo PC synthesis a role in dietary lipid absorption during of intestinal CTα and secretion and circulating and concentrations, phospholipid synthesis to and an unexpected role for intestinal de novo PC synthesis in the maintenance of normal enterohepatic of bile by the expression of the bile-acid in the a normal response to dietary fat de novo PC synthesis in the intestinal and the reacylation of PC derived from cannot The for and for and the of and for critical of the Jacobs for critical of the and for with of the of and of the CTP:phosphocholine cytidylyltransferase acid glucagon-like peptide 1 high-fat 2 cholesterol 1 phosphatidylcholine phosphatidylethanolamine peptide 2 triglyceride

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