Identification and Characterization of a Major Liver Lysophosphatidylcholine Acyltransferase

Abstract

Phosphatidylcholine (PC) is synthesized through the Kennedy pathway, but more than 50% of PC is remodeled through the Lands cycle, i.e. the deacylation and reacylation of PC to attain the final and proper fatty acids within PC. The reacylation step is catalyzed by lysophosphatidylcholine acyltransferase (LPCAT), and we report here the identification of a novel LPCAT, which we named LPCAT3. LPCAT3 belongs to the membrane-bound O-acyltransferase (MBOAT) family and encodes a protein of 487 amino acids with a calculated molecular mass of 56 kDa. Membranes from HEK293 cells overexpressing LPCAT3 showed significantly increased LPCAT activity as assessed by thin layer chromatography analysis with substrate preference toward unsaturated fatty acids. LPCAT3 is localized within the endoplasmic reticulum and is primarily expressed in metabolic tissues including liver, adipose, and pancreas. In a human hepatoma Huh7 cells, RNA interference-mediated knockdown of LPCAT3 resulted in virtually complete loss of membrane LPCAT activity, suggesting that LPCAT3 is primarily responsible for hepatic LPCAT activity. Furthermore, peroxisome proliferator-activated receptor α agonists dose-dependently regulated LPCAT3 in liver in a peroxisome proliferator-activated receptor α-dependent fashion, implicating a role of LPCAT3 in lipid homeostasis. Our studies identify a long-sought enzyme that plays a critical role in PC remodeling in metabolic tissues and provide an invaluable tool for future investigations on how PC remodeling may potentially impact glucose and lipid homeostasis. Phosphatidylcholine (PC) is synthesized through the Kennedy pathway, but more than 50% of PC is remodeled through the Lands cycle, i.e. the deacylation and reacylation of PC to attain the final and proper fatty acids within PC. The reacylation step is catalyzed by lysophosphatidylcholine acyltransferase (LPCAT), and we report here the identification of a novel LPCAT, which we named LPCAT3. LPCAT3 belongs to the membrane-bound O-acyltransferase (MBOAT) family and encodes a protein of 487 amino acids with a calculated molecular mass of 56 kDa. Membranes from HEK293 cells overexpressing LPCAT3 showed significantly increased LPCAT activity as assessed by thin layer chromatography analysis with substrate preference toward unsaturated fatty acids. LPCAT3 is localized within the endoplasmic reticulum and is primarily expressed in metabolic tissues including liver, adipose, and pancreas. In a human hepatoma Huh7 cells, RNA interference-mediated knockdown of LPCAT3 resulted in virtually complete loss of membrane LPCAT activity, suggesting that LPCAT3 is primarily responsible for hepatic LPCAT activity. Furthermore, peroxisome proliferator-activated receptor α agonists dose-dependently regulated LPCAT3 in liver in a peroxisome proliferator-activated receptor α-dependent fashion, implicating a role of LPCAT3 in lipid homeostasis. Our studies identify a long-sought enzyme that plays a critical role in PC remodeling in metabolic tissues and provide an invaluable tool for future investigations on how PC remodeling may potentially impact glucose and lipid homeostasis. The biomembrane lipid bilayer serves as an important structure that compartmentalizes living cells and also forms organized intracellular membrane organelles for various physiological functions. The major and essential structural components of membrane lipid bilayers are phospholipids (PLs) including phosphatidylcholine (PC), 2The abbreviations used are:PCphosphatidylcholinePPARαperoxisome proliferator-activated receptor αLPClysophosphatidylcholineLPSlysophosphatidylserineLPAlysophosphatidic acidLPGlysophosphatidylglycerolLPElysophosphatidylethanolamineLPIlysophosphatidylinositolPSphosphatidylserinePEphosphatidylethanolaminePGphosphatidylglycerolPAphosphatidic acidPIphosphatidylinositolMBOATmembrane-bound O-acyltransferaseDGAT1diacylglyerol acyltransferase 1LPSATlysophosphatidylserine acyltransferasePLphospholipidDGdiacylglyerolAGPATacyl-CoA:acylglycerol-3-phosphate acyltransferaseLPCATlysophosphatidylcholine acyltransferaseERendoplasmic reticulumGAPDHglyceraldehyde-3-phosphate dehydrogenasesiRNAsmall interfering RNALPAATlysophosphatidic acid acyltransferaseLPGATlysophosphatidylglycerol acyltransferase. phosphatidylserine (PS), and phosphatidylethanolamine (PE), among which PC is the most abundant in mammals. Besides the fundamental role in maintaining the membrane structure, some PLs such as phosphatidylinositol (PI) and diacylglycerol (DG) play important roles in signal transduction. The pathway of PL de novo synthesis has been pioneered and elegantly elucidated by Dr. Eugene Kennedy and colleagues (1Kennedy E.P. Vance D.E. Phosphatidylcholine Metabolism. CRC Press, Boca Raton, FL1989: 1-9Google Scholar). phosphatidylcholine peroxisome proliferator-activated receptor α lysophosphatidylcholine lysophosphatidylserine lysophosphatidic acid lysophosphatidylglycerol lysophosphatidylethanolamine lysophosphatidylinositol phosphatidylserine phosphatidylethanolamine phosphatidylglycerol phosphatidic acid phosphatidylinositol membrane-bound O-acyltransferase diacylglyerol acyltransferase 1 lysophosphatidylserine acyltransferase phospholipid diacylglyerol acyl-CoA:acylglycerol-3-phosphate acyltransferase lysophosphatidylcholine acyltransferase endoplasmic reticulum glyceraldehyde-3-phosphate dehydrogenase small interfering RNA lysophosphatidic acid acyltransferase lysophosphatidylglycerol acyltransferase. PLs are known to be remodeled after their de novo synthesis through deacylation and reacylation processes to acquire their appropriate fatty acid composition. This deacylation and reacylation process, defined as the Lands cycle, may be critical for proper membrane fluidity, vesicle trafficking, and other relevant biological functions (2Lands W.E. J. Biol. Chem. 1960; 235: 2233-2237Abstract Full Text PDF PubMed Google Scholar, 3Lands W.E. Merkl I. J. Biol. Chem. 1963; 238: 898-904Abstract Full Text PDF PubMed Google Scholar, 4Merkl I. Lands W.E. J. Biol. Chem. 1963; 238: 905-906Abstract Full Text PDF PubMed Google Scholar, 5MacDonald J.I. Sprecher H. Biochim. Biophys. Acta. 1991; 1084: 105-121Crossref PubMed Scopus (248) Google Scholar). In pancreatic β cells, PL remodeling is believed to play an essential role in amplifying the signal for insulin secretion; and in hepatocytes, proper PL composition appears vital for very low-density lipoprotein assembly and secretion (6Bao S. Bohrer A. Ramanadham S. Jin W. Zhang S. Turk J. J. Biol. Chem. 2006; 281: 187-198Abstract Full Text Full Text PDF PubMed Scopus (64) Google Scholar, 7Tran K. Sun F. Cui Z. Thorne-Tjomsland G. St. Germain C. Lapierre L.R. McLeod R.S. Jamieson J.C. Yao Z. Biochim. Biophys. Acta. 2006; 1761: 463-473Crossref PubMed Scopus (29) Google Scholar). The saturated fatty acids found frequently at the sn-1 position of PC are believed to be derived from de novo biosynthesis, whereas the unsaturated fatty acids, usually found at the sn-2 position in PC, are esterified mainly through the remodeling process (5MacDonald J.I. Sprecher H. Biochim. Biophys. Acta. 1991; 1084: 105-121Crossref PubMed Scopus (248) Google Scholar). Indeed, the two acyl-CoA:acylglycerol-3-phosphate acyltransferase (AGPAT) enzymes described in recent years do not appear to have specific substrate preference toward fatty acyl-CoAs at the sn-2 position within the de novo PC biosynthetic pathway (8Aguado B. Campbell R.D. J. Biol. Chem. 1998; 273: 4096-4105Abstract Full Text Full Text PDF PubMed Scopus (90) Google Scholar, 9Eberhardt C. Gray P.W. Tjoelker L.W. J. Biol. Chem. 1997; 272: 20299-20305Abstract Full Text Full Text PDF PubMed Scopus (121) Google Scholar). In contrast, fatty acyl chain at the sn-2 position of PC is believed to be hydrolyzed by a specific phospholipid lipase A2 family member, which is then re-acylated by the lysophosphatidylcholine acyltransferases (LPCAT). LPCAT activity has been found to reside primarily in microsomal fractions of tissues and characterization of this activity using microsomes from various tissues has led to the hypothesis that multiple forms of enzymes may exist in different tissues with different substrate specificity of fatty acyl-CoAs (5MacDonald J.I. Sprecher H. Biochim. Biophys. Acta. 1991; 1084: 105-121Crossref PubMed Scopus (248) Google Scholar, 10Choy P.C. Skrzypczak M. Lee D. Jay F.T. Biochim. Biophys. Acta. 1997; 1348: 124-133Crossref PubMed Scopus (26) Google Scholar). Attempts to purify the enzyme(s) have not been successful historically largely due to its membrane protein nature and the fact that LPCAT activity was mostly lost during solubilization and/or further fractionation (5MacDonald J.I. Sprecher H. Biochim. Biophys. Acta. 1991; 1084: 105-121Crossref PubMed Scopus (248) Google Scholar, 10Choy P.C. Skrzypczak M. Lee D. Jay F.T. Biochim. Biophys. Acta. 1997; 1348: 124-133Crossref PubMed Scopus (26) Google Scholar). However, through genomic efforts, Chen and colleagues (11Chen X. Hyatt B.A. Mucenski M.L. Mason R.J. Shannon J.M. Proc. Natl. Acad. Sci. U. S. A. 2006; 103: 11724-11729Crossref PubMed Scopus (154) Google Scholar) and Nakanishi and colleagues (12Nakanishi H. Shindou H. Hishikawa D. Harayama T. Ogasawara R. Suwabe A. Taguchi R. Shimizu T. J. Biol. Chem. 2006; 281: 20140-20147Abstract Full Text Full Text PDF PubMed Scopus (188) Google Scholar) recently reported the cloning of a distinctive LPCAT1 that is specifically expressed in lung alveolar type II cells and favors saturated fatty acyl-CoAs as substrates. A second LPCAT (LPCAT2) was also reported that is also an acetylCoA:lyso platelet-activating factor acyltransferase (lyso-PAFAT) with relatively broad tissue distribution (13Shindou H. Hishikawa D. Nakanishi H. Harayama T. Ishii S. Taguchi R. Shimizu T. J. Biol. Chem. 2007; 282: 6532-6539Abstract Full Text Full Text PDF PubMed Scopus (187) Google Scholar). LPCAT activity from liver microsomes indicated that the liver LPCAT prefers unsaturated fatty acyl-CoA as substrates but the identity of this enzyme has yet to be determined (14Lands W.E. Inoue M. Sugiura Y. Okuyama H. J. Biol. Chem. 1982; 257: 14968-14972Abstract Full Text PDF PubMed Google Scholar). Here we report the identification and characterization of such an enzyme, which we named LPCAT3. LPCAT3 belongs to the MBOAT family and is localized to the ER and most abundantly expressed in liver, pancreas, and adipose. Importantly, LPCAT3 prefers unsaturated fatty acyl-CoAs as substrates and appears to be the only such enzyme in liver responsible for this function. Materials—Various lysophospholipids and acyl-CoAs were purchased from Avanti Polar Lipids (Alabaster, AL). 14C-Labeled lysophospholipids, acyl-CoAs, and phospholipids were ordered from American Radiolabeled Chemicals (St. Louis, MO). Plasmid Construction—A full-length human LPCAT3 coding cDNA (NCBI accession number NM_005768) was purchased from Invitrogen. The C-terminal FLAG-tagged LPCAT3 was generated by PCR and subcloned into the pCR8/GW/TOPO vector (Invitrogen). The sequences of the primers are as follows: 5′-TCCACCATGGCGTCCTCAGCGGAGG-3′ (forward) and 5′-TCACTTATCGTCCTCATCCTTGTAATCAGCAGCAGCTTCCATCTTCTTTAA-3′ (reverse). The LPCAT3-FLAG fusion was transferred to the pcDNA3.2V5/DEST vector using LR Clonase II (Invitrogen) following the manufacturer's instructions. The human LPCAT1 (SC112001), LPCAT2 (SC100893), GPAM (SC106982), LPGAT1 (SC121130), and AGPAT2 (SC116102) cDNA were purchased from Origene Technologies (Rockville, MD). The sequences of all the constructs were confirmed by sequencing from both directions. Cell Culture, Transfection, and Membrane Protein Preparation—Human 293, COS-7, and Huh7 cells were purchased from American Type Culture Collection (Manassas, VA) and cultured in Dulbecco's modified Eagle's/F-12 (3:1) medium supplemented with 5% fetal bovine serum in a humidified air atmosphere containing 5% CO2. For transfections, 5 × 105 293 cells, 1 × 105 COS-7 cells, or 2 × 105 Huh7 cells were seeded in 6-well plates (Falcon, Corning, NY). 1 μg of DNA was transfected using FuGENE 6 (Roche Diagnostics) in each experiment according to the manufacturer's instructions. 48 h after transfection, cells were scraped into 150 μl of ice-cold buffer containing 20 mm Tris-HCl (pH 7.5), 250 mm sucrose, 1 mm EDTA, and a protease inhibitor mixture (Roche Diagnostics), and then sonicated three times on ice for 30 s. After centrifugation for 10 min at 1,000 × g, the supernatant was centrifuged at 100,000 × g for 1 h. The pellet as the membrane fraction was resuspended in the same buffer and frozen at –80 °C until use. Protein concentrations were determined using a commercially prepared protein assay kit (Pierce) and bovine serum albumin as a standard. Expression of FLAG-tagged LPCAT3 was verified by Western blot analysis with a mouse anti-FLAG monoclonal antibody (Sigma). In Vitro Acyltransferase Activity Assays—Acyltransferase activity was determined by measuring the incorporation of radiolabeled acyl-CoAs into phospholipids. The reaction mixture in a total volume of 100 μl contained mm Tris-HCl (pH 7.5), 1 fatty bovine serum of each 20 and 5 membrane from HEK293 cells transfected with or The reaction was by the of the membrane for 20 min at and was by 1 of The phospholipids were by the of and J. PubMed Scopus Google Scholar). The was air and by thin layer chromatography using as the by to a The was used for analysis to and cells were transfected with LPCAT3-FLAG on 48 h cells were with 100 (Invitrogen) for 10 min at The cells were with for 20 min at °C and with in The were then for 2 h at with a mouse anti-FLAG monoclonal antibody or a antibody in with bovine serum After with the were for 1 h at with or (Invitrogen). The cells were with (Invitrogen) to the was with an with a LPCAT3-FLAG was by at and with a reticulum and were by at and with a For the of the was at and were with a and RNA was purchased from and the cDNA was synthesized from of RNA the for The ordered from were and PCR was on PCR using PCR were using glyceraldehyde-3-phosphate dehydrogenase was used as a The were by the to of human LPCAT3 and and were transfected using (Invitrogen) according to the manufacturer's The was for 2 in Huh7 RNA from the transfected cells was for and The membrane from the transfected cells were prepared for the in acyltransferase activity were in with and and and peroxisome proliferator-activated receptor were purchased from and for 2 the of the The were and the were at various concentrations in and by for The were h after the final by for serum were by were and frozen in and used for are as among were by analysis of with using A was to in recent years have a family of and a family of membrane-bound K. Sci. Full Text Full Text PDF PubMed Scopus Google Scholar, Lee PubMed Scopus Google Scholar, X. S. R. M. K. J. 2006; Full Text Full Text PDF PubMed Scopus Google Scholar). The roles for most of have not been of family have been as acyltransferase S. S. C. Proc. Natl. Acad. Sci. U. S. A. 1998; PubMed Scopus Google lysophosphatidic acid acyltransferase (8Aguado B. Campbell R.D. J. Biol. Chem. 1998; 273: 4096-4105Abstract Full Text Full Text PDF PubMed Scopus (90) Google Scholar, 9Eberhardt C. Gray P.W. Tjoelker L.W. J. Biol. Chem. 1997; 272: 20299-20305Abstract Full Text Full Text PDF PubMed Scopus (121) Google lysophosphatidylglycerol acyltransferase Y. J. Y. J. Biol. Chem. Full Text Full Text PDF PubMed Scopus Google and acyltransferase J. Y. J. Y. J. Biol. Chem. Full Text Full Text PDF PubMed Scopus Google Scholar). on the acyltransferases for LPCAT activity to identify the LPCAT in were subcloned into an vector and the were expressed in HEK293 Membranes were then prepared and for LPCAT activity as described of the the human membrane-bound O-acyltransferase 5 LPCAT activity and was further the LPCAT activity of human LPCAT3 in the whereas human LPCAT1 and LPCAT2 were used as to was reported by S. R. A. J. 2007; PubMed Scopus Google human LPCAT1 LPCAT activity with vector and acyl-CoA acyltransferase as with the by Chen (11Chen X. Hyatt B.A. Mucenski M.L. Mason R.J. Shannon J.M. Proc. Natl. Acad. Sci. U. S. A. 2006; 103: 11724-11729Crossref PubMed Scopus (154) Google Scholar) and Nakanishi (12Nakanishi H. Shindou H. Hishikawa D. Harayama T. Ogasawara R. Suwabe A. Taguchi R. Shimizu T. J. Biol. Chem. 2006; 281: 20140-20147Abstract Full Text Full Text PDF PubMed Scopus (188) Google Scholar) using mouse LPCAT1 LPCAT2 very LPCAT activity in activity was confirmed in a not virtually LPCAT activity to that of LPCAT1 and we as LPCAT3. of the fact that we do not the protein the activity of each LPCAT not be of a at the of the protein but largely LPCAT activity. In LPCAT3 also lysophosphatidylserine acyltransferase activity the substrate specificity of LPCAT3 other lysophospholipids, acid lysophosphatidylglycerol lysophosphatidylethanolamine and lysophosphatidylinositol were used as substrates with LPCAT3 not activity whereas AGPAT2 and LPGAT1 and or as LPCAT3 is a specific LPCAT and The complete amino acid of human LPCAT3 from the cDNA is in The protein has 487 amino acids and the at the as a ER In to other LPCAT3 not a that is among acyltransferase family Lee PubMed Scopus Google Scholar). The that is among the membrane-bound O-acyltransferase is The of the with of human diacylglyerol acyltransferase acyltransferase 1 and 2 multiple amino acids including the and in the MBOAT implicating roles of amino acids in substrate or or maintaining the proper structure for such of the LPCAT structure the of and a membrane expressed in HEK293 cells and using Western the protein an molecular mass of 56 with the molecular mass from the The LPCAT3 substrate specificity was further in three using as a different fatty acyl-CoAs were as acyl in the same the saturated fatty acyl-CoAs, only activity with unsaturated fatty and all LPCAT activity the specificity of was using different fatty acyl at the sn-1 position of all the different substrates and the most activity, whereas activity was using and as substrates using as the different fatty acyl-CoAs were within the same experiment with their activity. unsaturated fatty acyl-CoAs activity than saturated fatty acyl-CoAs and in to in a further in activity In LPCAT3 favors unsaturated fatty acyl-CoAs as acyl with saturated fatty then studies using and different fatty acyl-CoAs as the substrates and fatty acyl-CoA concentrations resulted in increased LPCAT activity. The and were calculated and are in the unsaturated fatty acyl-CoAs have than of saturated fatty acyl-CoAs, the are in The of the as by using different acyl is using as the increased concentrations led to increased LPCAT activity an reaction of of and an of of in a The of LPCAT3 was using LPCAT3 with the at the was expressed in cells, and was using an antibody the ER protein and a were used as 5 that of LPCAT3 with that of its ER with this was of LPCAT3 with the not The tissue distribution of human LPCAT3 was with PCR as described The of was in liver, by and tissue of were in other and very of LPCAT3 The of human LPCAT3 its in the of human LPCAT3 to total LPCAT activity, we used knockdown to LPCAT3 in human hepatoma Huh7 cells to of the with two different The LPCAT3 resulted in more than membrane LPCAT activity with the and This that LPCAT3 is the major enzyme to LPCAT activity in Huh7 cells and liver in is a receptor that fatty acid and in lipoprotein B. J. J. K. J.C. 1998; PubMed Scopus Google Scholar). chain fatty acids are believed to be for B. J. J. K. J.C. 1998; PubMed Scopus Google Scholar). of the of LPCAT3 in the liver and its to lipid its by agonists was were with agonists for and liver LPCAT3 were a in dose-dependently liver LPCAT3 with of A also dose-dependently increased liver LPCAT3 by this was in the of LPCAT3 by two was specifically by report here the identification and characterization of a novel LPCAT, which we named LPCAT3. that LPCAT3 is the long-sought liver LPCAT on the following Membranes from HEK293 cells overexpressing LPCAT3 have increased LPCAT activity. LPCAT3 is localized within with the that LPCAT activity is largely LPCAT3 prefers unsaturated fatty acyl-CoAs as which is in with the characterization of LPCAT activity using liver LPCAT3 is expressed in of LPCAT3 through in hepatoma Huh7 cells resulted in of membrane LPCAT activity. has been known for years that PC a remodeling process in and tissue primarily at the sn-2 position The of Press, Scholar). has also been that more than 50% of PC is from PC remodeling (2Lands W.E. J. Biol. Chem. 1960; 235: 2233-2237Abstract Full Text PDF PubMed Google Scholar, 5MacDonald J.I. Sprecher H. Biochim. Biophys. Acta. 1991; 1084: 105-121Crossref PubMed Scopus (248) Google Scholar, 10Choy P.C. Skrzypczak M. Lee D. Jay F.T. Biochim. Biophys. Acta. 1997; 1348: 124-133Crossref PubMed Scopus (26) Google Scholar). PL remodeling is a step to attain the appropriate fatty acyl within PL to the proper membrane structure for a of physiological functions the de novo PL biosynthetic enzymes appear to have very substrate specificity P.C. Skrzypczak M. Lee D. Jay F.T. Biochim. Biophys. Acta. 1997; 1348: 124-133Crossref PubMed Scopus (26) Google Scholar). The reacylation of catalyzed by has been primarily within microsomal fractions The of Press, Scholar). has been that different may exist in different or tissues on the studies using microsomal from different cells and tissues (5MacDonald J.I. Sprecher H. Biochim. Biophys. Acta. 1991; 1084: 105-121Crossref PubMed Scopus (248) Google Scholar, 10Choy P.C. Skrzypczak M. Lee D. Jay F.T. Biochim. Biophys. Acta. 1997; 1348: 124-133Crossref PubMed Scopus (26) Google Scholar). Indeed, Chen (11Chen X. Hyatt B.A. Mucenski M.L. Mason R.J. Shannon J.M. Proc. Natl. Acad. Sci. U. S. A. 2006; 103: 11724-11729Crossref PubMed Scopus (154) Google Scholar) and Nakanishi (12Nakanishi H. Shindou H. Hishikawa D. Harayama T. Ogasawara R. Suwabe A. Taguchi R. Shimizu T. J. Biol. Chem. 2006; 281: 20140-20147Abstract Full Text Full Text PDF PubMed Scopus (188) Google Scholar) reported the cloning of an LPCAT with specifically in alveolar type II cells in This enzyme prefers saturated fatty acyl-CoA and is to be primarily responsible for in LPCAT with activity in assay is also a with a role in cells (13Shindou H. Hishikawa D. Nakanishi H. Harayama T. Ishii S. Taguchi R. Shimizu T. J. Biol. Chem. 2007; 282: 6532-6539Abstract Full Text Full Text PDF PubMed Scopus (187) Google Scholar). The LPCAT we we named is expressed primarily in metabolic tissues pancreas, and LPCAT3 has LPCAT activity with that of but has substrate specificity in that prefers unsaturated fatty acids. Our with the hypothesis that different enzyme forms with substrate specificity exist and are to specific physiological functions in different cells or In knockdown experiment in Huh7 cells that LPCAT3 is primarily responsible for the LPCAT activity in is to that LPCAT3 has activity toward not activity and a recently membrane-bound O-acyltransferase has relatively broad substrate all the S. B. M. C. J. Biol. Chem. 2007; 282: Full Text Full Text PDF PubMed Scopus Google Scholar, J. S. J. Biol. Chem. 2007; 282: Full Text Full Text PDF PubMed Scopus Google Scholar, J. J. Biol. Chem. 2007; 282: Full Text Full Text PDF PubMed Scopus Google Scholar, M. C. J. A. J. Biol. Chem. 2007; 282: Full Text Full Text PDF PubMed Scopus Google Scholar, H. A. Y. M. J. M. H. H. R. H. J. Biol. Chem. 2007; 282: Full Text Full Text PDF PubMed Scopus Google Scholar). is that specific assay may have from such forms of and acyltransferases in may exist in to the in of and were reported in recent whereas and acyltransferases have yet to be using liver microsomes the of such and a and/or W.E. Merkl I. J. Biol. Chem. 1963; 238: 898-904Abstract Full Text PDF PubMed Google Scholar). The physiological of PC remodeling is not appears that the remodeling process is for cells to acquire the appropriate PC composition for specific functions. Our an invaluable tool for future investigations in this Importantly, LPCAT3 has a very in liver, pancreas, and is known that in pancreatic PC remodeling is an important step in for insulin The of acid and may have important functions in this process (6Bao S. Bohrer A. Ramanadham S. Jin W. Zhang S. Turk J. J. Biol. Chem. 2006; 281: 187-198Abstract Full Text Full Text PDF PubMed Scopus (64) Google Scholar). The role of LPCAT be to the appropriate PC substrates for the by A2 or to to PC to the insulin The of the role of LPCAT in this process is In hepatocytes, PC and composition may impact lipoprotein secretion K. Sun F. Cui Z. Thorne-Tjomsland G. St. Germain C. Lapierre L.R. McLeod R.S. Jamieson J.C. Yao Z. Biochim. Biophys. Acta. 2006; 1761: 463-473Crossref PubMed Scopus (29) Google Scholar, H. J. J. Biol. Chem. Full Text Full Text PDF PubMed Scopus Google the of LPCAT3 in lipid be an to in the In this is important to that Yao and H. J. J. Biol. Chem. Full Text Full Text PDF PubMed Scopus Google Scholar) recently that PC in Huh7 cells from chain fatty acyl-CoA significantly and is a receptor that primarily fatty acid also important for and homeostasis. The for are believed to be chain fatty acids. Our that LPCAT3 is specifically regulated by agonists in a further a role for LPCAT3 in lipid The role of LPCAT3 in a of physiological processes have to future in and in Dr. for with for of PCR and and for of in