Lcat

Summary

Gene Symbol: Lcat
Description: lecithin cholesterol acyltransferase
Alias: AI046659, D8Wsu61e, phosphatidylcholine-sterol acyltransferase, lecithin-cholesterol acyltransferase Lcat, phospholipid-cholesterol acyltransferase
Species: mouse
Products:     Lcat

Top Publications

  1. Ng D. The role of lecithin:cholesterol acyltransferase in the modulation of cardiometabolic risks - a clinical update and emerging insights from animal models. Biochim Biophys Acta. 2012;1821:654-9 pubmed publisher
    Lecithin cholesterol acyltransferase (LCAT) is the key enzyme in mediating the esterification of cholesterol on circulating lipoproteins...
  2. Roghani A, Welch C, Xia Y, Liu Y, Peter D, Finn J, et al. Assignment of the mouse vesicular monoamine transporter genes, Slc18a1 and Slc18a2, to chromosomes 8 and 19 by linkage analysis. Mamm Genome. 1996;7:393-4 pubmed
  3. Temel R, Parks J, Williams D. Enhancement of scavenger receptor class B type I-mediated selective cholesteryl ester uptake from apoA-I(-/-) high density lipoprotein (HDL) by apolipoprotein A-I requires HDL reorganization by lecithin cholesterol acyltransferase. J Biol Chem. 2003;278:4792-9 pubmed
    ..These data suggest that the conformation of apoA-I at the HDL surface is important for the efficient transfer of CE to the cell. ..
  4. Subbaiah P, Jiang X, Belikova N, Aizezi B, Huang Z, Reardon C. Regulation of plasma cholesterol esterification by sphingomyelin: effect of physiological variations of plasma sphingomyelin on lecithin-cholesterol acyltransferase activity. Biochim Biophys Acta. 2012;1821:908-13 pubmed publisher
    ..models of mice which naturally differ in their plasma SM/PC ratios, to study the role of SM as a modulator of LCAT, the enzyme responsible for HDL maturation and the synthesis of cholesteryl esters (CE) in normal plasma...
  5. Wu C, Tsujita M, Okumura Noji K, Usui S, Kakuuchi H, Okazaki M, et al. Cholesteryl ester transfer protein expressed in lecithin cholesterol acyltransferase-deficient mice. Arterioscler Thromb Vasc Biol. 2002;22:1347-53 pubmed
    ..plasma cholesteryl ester transfer protein (CETP) concentration was studied in lecithin-cholesterol acyltransferase (LCAT)-knockout mice. LCAT-knockout mice were cross-bred with CETP transgenic mice...
  6. Rogers M, Liu J, Kushnir M, Bryleva E, Rockwood A, Meikle A, et al. Cellular pregnenolone esterification by acyl-CoA:cholesterol acyltransferase. J Biol Chem. 2012;287:17483-92 pubmed publisher
    Pregnenolone (PREG) can be converted to PREG esters (PE) by the plasma enzyme lecithin: cholesterol acyltransferase (LCAT), and by other enzyme(s) with unknown identity...
  7. Gerhard G, Kaufmann E, Wang X, Erikson K, Abraham J, Grundy M, et al. Genetic differences in hepatic lipid peroxidation potential and iron levels in mice. Mech Ageing Dev. 2002;123:167-76 pubmed
    ..0006. At least two potentially relevant candidate genes reside close to this chromosomal position. Hepatic lipid peroxidation potential appears to be a strain related trait in mice that is amenable to QTL analysis. ..
  8. Belalcazar M, Chan L. Somatic gene therapy for dyslipidemias. J Lab Clin Med. 1999;134:194-214 pubmed
    ..We highlight some recent advances in adenoviral vector development that make this vector an attractive system for clinical trials. ..
  9. Furbee J, Francone O, Parks J. In vivo contribution of LCAT to apolipoprotein B lipoprotein cholesteryl esters in LDL receptor and apolipoprotein E knockout mice. J Lipid Res. 2002;43:428-37 pubmed
    Previous studies have indicated that LCAT may play a role in the generation of cholesteryl esters (CE) in plasma apolipoprotein B (apoB) lipoproteins...

More Information

Publications55

  1. Shike T, Hirose S, Kobayashi M, Funabiki K, Shirai T, Tomino Y. Susceptibility and negative epistatic loci contributing to type 2 diabetes and related phenotypes in a KK/Ta mouse model. Diabetes. 2001;50:1943-8 pubmed
    ..However, there appear to be common genes contributing to different disease phenotypes. There are potentially important candidate genes that may be relevant to the disease. ..
  2. Taschler U, Radner F, Heier C, Schreiber R, Schweiger M, Schoiswohl G, et al. Monoglyceride lipase deficiency in mice impairs lipolysis and attenuates diet-induced insulin resistance. J Biol Chem. 2011;286:17467-77 pubmed publisher
    ..Defective degradation of 2-AG does not provoke cannabinoid-like effects on feeding behavior, lipid storage, and energy expenditure, which may be explained by desensitization of CBR. ..
  3. Dixon J, Kim Y, Brinker A, Quadro L. Loss of ?-carotene 15,15'-oxygenase in developing mouse tissues alters esterification of retinol, cholesterol and diacylglycerols. Biochim Biophys Acta. 2014;1841:34-43 pubmed publisher
    ..Furthermore, LCAT, ACAT1 and DGAT2 mRNA levels were also downregulated in CMOI-/- embryos...
  4. Rooke K, Briquet Laugier V, Xia Y, Lusis A, Doolittle M. Mapping of the gene for calreticulin (Calr) to mouse chromosome 8. Mamm Genome. 1997;8:870-1 pubmed
  5. Ng D, Francone O, Forte T, Zhang J, Haghpassand M, Rubin E. Disruption of the murine lecithin:cholesterol acyltransferase gene causes impairment of adrenal lipid delivery and up-regulation of scavenger receptor class B type I. J Biol Chem. 1997;272:15777-81 pubmed
    Lecithin:cholesterol acyltransferase (LCAT) is the major determinant of the cholesteryl ester (CE) content of high density lipoprotein (HDL) in plasma...
  6. Ossoli A, Neufeld E, Thacker S, Vaisman B, Pryor M, Freeman L, et al. Lipoprotein X Causes Renal Disease in LCAT Deficiency. PLoS ONE. 2016;11:e0150083 pubmed publisher
    Human familial lecithin:cholesterol acyltransferase (LCAT) deficiency (FLD) is characterized by low HDL, accumulation of an abnormal cholesterol-rich multilamellar particle called lipoprotein-X (LpX) in plasma, and renal disease...
  7. Hager L, Li L, Pun H, Liu L, Hossain M, Maguire G, et al. Lecithin:cholesterol acyltransferase deficiency protects against cholesterol-induced hepatic endoplasmic reticulum stress in mice. J Biol Chem. 2012;287:20755-68 pubmed publisher
    We recently reported that lecithin:cholesterol acyltransferase (LCAT) knock-out mice, particularly in the LDL receptor knock-out background, are hypersensitive to insulin and resistant to high fat diet-induced insulin resistance (IR) and ..
  8. Furbee J, Sawyer J, Parks J. Lecithin:cholesterol acyltransferase deficiency increases atherosclerosis in the low density lipoprotein receptor and apolipoprotein E knockout mice. J Biol Chem. 2002;277:3511-9 pubmed
    The purpose of the present study was to test the hypothesis that lecithin:cholesterol acyltransferase (LCAT) deficiency would accelerate atherosclerosis development in low density lipoprotein (LDL) receptor (LDLr-/-) and apoE (apoE-/-) ..
  9. Song H, Zhu L, Picardo C, Maguire G, Leung V, Connelly P, et al. Coordinated alteration of hepatic gene expression in fatty acid and triglyceride synthesis in LCAT-null mice is associated with altered PUFA metabolism. Am J Physiol Endocrinol Metab. 2006;290:E17-E25 pubmed
    Complete lecithin:cholesterol acyltransferase (LCAT) deficiency is associated with fasting hypertriglyceridemia (HTG)...
  10. Zhao Y, Thorngate F, Weisgraber K, Williams D, Parks J. Apolipoprotein E is the major physiological activator of lecithin-cholesterol acyltransferase (LCAT) on apolipoprotein B lipoproteins. Biochemistry. 2005;44:1013-25 pubmed
    Our previous studies have indicated that lecithin-cholesterol acyltransferase (LCAT) contributes significantly to the apoB lipoprotein cholesteryl ester (CE) pool...
  11. Duka A, Fotakis P, Georgiadou D, Kateifides A, Tzavlaki K, von Eckardstein L, et al. ApoA-IV promotes the biogenesis of apoA-IV-containing HDL particles with the participation of ABCA1 and LCAT. J Lipid Res. 2013;54:107-15 pubmed publisher
    The objective of this study was to establish the role of apoA-IV, ABCA1, and LCAT in the biogenesis of apoA-IV-containing HDL (HDL-A-IV) using different mouse models...
  12. Fournier N, Atger V, Paul J, de la Llera Moya M, Rothblat G, Moatti N. Fractional efflux and net change in cellular cholesterol content mediated by sera from mice expressing both human apolipoprotein AI and human lecithin:cholesterol acyltransferase genes. Atherosclerosis. 1999;147:227-35 pubmed
    Human lecithin:cholesterol acyltransferase (LCAT) is a key enzyme in the metabolism of cholesterol and is postulated to participate in the physiological process called reverse cholesterol transport...
  13. Forte T, Oda M, Knoff L, Frei B, Suh J, Harmony J, et al. Targeted disruption of the murine lecithin:cholesterol acyltransferase gene is associated with reductions in plasma paraoxonase and platelet-activating factor acetylhydrolase activities but not in apolipoprotein J concentration. J Lipid Res. 1999;40:1276-83 pubmed
    Lecithin:cholesteryl acyltransferase (LCAT) deficiency resulting from targeted disruption of the Lcat gene in the mouse is associated with dramatic decreases in HDL concentration and the accumulation of nascent HDL in the plasma...
  14. Webb N, De Beer M, van der Westhuyzen D, Kindy M, Banka C, Tsukamoto K, et al. Adenoviral vector-mediated overexpression of serum amyloid A in apoA-I-deficient mice. J Lipid Res. 1997;38:1583-90 pubmed
    ..We conclude that SAA is unable to substitute for apoA-I in HDL particle formation. ..
  15. Petropoulou P, Berbee J, Theodoropoulos V, Hatziri A, Stamou P, Karavia E, et al. Lack of LCAT reduces the LPS-neutralizing capacity of HDL and enhances LPS-induced inflammation in mice. Biochim Biophys Acta. 2015;1852:2106-15 pubmed publisher
    ..As lecithin-cholesterol acyltransferase (LCAT) is a critical enzyme in the maturation of HDL we investigated whether LCAT-deficient (Lcat(-/-)) mice present an ..
  16. Warden C, Langner C, Gordon J, Taylor B, McLean J, Lusis A. Tissue-specific expression, developmental regulation, and chromosomal mapping of the lecithin: cholesterol acyltransferase gene. Evidence for expression in brain and testes as well as liver. J Biol Chem. 1989;264:21573-81 pubmed
    Lecithin:cholesterol acyltransferase (LCAT) catalyzes the esterification of cholesterol in high density lipoproteins, thereby facilitating transport of excess cholesterol from peripheral tissues to liver...
  17. Stukas S, Freeman L, Lee M, Wilkinson A, Ossoli A, Vaisman B, et al. LCAT deficiency does not impair amyloid metabolism in APP/PS1 mice. J Lipid Res. 2014;55:1721-9 pubmed publisher
    ..discoidal to spherical particles is the esterification of cholesterol to cholesteryl ester, which is catalyzed by LCAT. HDL-like lipoproteins in cerebrospinal fluid (CSF) are also spherical, whereas nascent lipoprotein particles ..
  18. Kim Y, Zuccaro M, Costabile B, Rodas R, Quadro L. Tissue- and sex-specific effects of β-carotene 15,15' oxygenase (BCO1) on retinoid and lipid metabolism in adult and developing mice. Arch Biochem Biophys. 2015;572:11-8 pubmed publisher
  19. Lee R, Kelley K, Sawyer J, Farese R, Parks J, Rudel L. Plasma cholesteryl esters provided by lecithin:cholesterol acyltransferase and acyl-coenzyme a:cholesterol acyltransferase 2 have opposite atherosclerotic potential. Circ Res. 2004;95:998-1004 pubmed
    ..ACAT2 is a proatherogenic enzyme that contributes cholesteryl esters (CEs) to apoB-containing lipoproteins, whereas LCAT is an antiatherogenic enzyme that facilitates reverse cholesterol transport by esterifying free cholesterol on HDL ..
  20. Zhang A, Gao S, Fan J, Huang W, Zhao T, Liu G. Increased plasma HDL cholesterol levels and biliary cholesterol excretion in hamster by LCAT overexpression. FEBS Lett. 2004;570:25-9 pubmed
    Lecithin cholesterol acyltransferase (LCAT) is a key enzyme in the metabolism of high density lipoprotein (HDL), which has been found inversely correlated with atherosclerosis...
  21. Pellegrino C, Rybicki A, Musto S, Nagel R, Schwartz R. Molecular identification and expression of erythroid K:Cl cotransporter in human and mouse erythroleukemic cells. Blood Cells Mol Dis. 1998;24:31-40 pubmed
  22. Forte T, Subbanagounder G, Berliner J, Blanche P, Clermont A, Jia Z, et al. Altered activities of anti-atherogenic enzymes LCAT, paraoxonase, and platelet-activating factor acetylhydrolase in atherosclerosis-susceptible mice. J Lipid Res. 2002;43:477-85 pubmed
    We examined whether the putative anti-atherogenic enzymes LCAT, paraoxonase (PON), and platelet-activating factor acetylhydrolase (PAF-AH) are impaired in 8 week old atherosclerosis susceptible apolipoprotein E (apoE)(-/-) and LDL ..
  23. Su W, Shmukler B, Chernova M, Stuart Tilley A, de Franceschi L, Brugnara C, et al. Mouse K-Cl cotransporter KCC1: cloning, mapping, pathological expression, and functional regulation. Am J Physiol. 1999;277:C899-912 pubmed
    ..These reagents and findings will expedite studies of KCC1 structure-function relationships and of the pathobiology of KCC1-mediated K-Cl cotransport. ..
  24. Lambert G, Sakai N, Vaisman B, Neufeld E, Marteyn B, Chan C, et al. Analysis of glomerulosclerosis and atherosclerosis in lecithin cholesterol acyltransferase-deficient mice. J Biol Chem. 2001;276:15090-8 pubmed
    ..and the variable development of atherosclerosis in patients with familial lecithin cholesterol acyl transferase (LCAT) deficiency, we generated LCAT knockout (KO) mice and cross-bred them with apolipoprotein (apo) E KO, low density ..
  25. Webb N, de Beer M, Asztalos B, Whitaker N, van der Westhuyzen D, de Beer F. Remodeling of HDL remnants generated by scavenger receptor class B type I. J Lipid Res. 2004;45:1666-73 pubmed
    ..Although LCAT-deficient plasma promoted only partial conversion, this deficiency was attributable to the nature of HDL particles ..
  26. Lee R, Shah R, Sawyer J, Hamilton R, Parks J, Rudel L. ACAT2 contributes cholesteryl esters to newly secreted VLDL, whereas LCAT adds cholesteryl ester to LDL in mice. J Lipid Res. 2005;46:1205-12 pubmed
    The relative contributions of ACAT2 and LCAT to the cholesteryl ester (CE) content of VLDL and LDL were measured. ACAT2 deficiency led to a significant decrease in the percentage of CE (37.2 +/- 2.1% vs. 3.9 +/- 0...
  27. She M, Li H, Yu L, Gu S, Wang Z. Inhibition of intimal lipid deposition in human apolipoprotein A1 transgenic mice. Clin Exp Pharmacol Physiol. 1999;26:833-4 pubmed
    ..Expression of platelet-derived growth factor-B, c-myc and c-fos proteins was much weaker in smooth muscle cells at the aortic sinus in transgenic mice. ..
  28. Fotakis P, Kuivenhoven J, Dafnis E, Kardassis D, Zannis V. The Effect of Natural LCAT Mutations on the Biogenesis of HDL. Biochemistry. 2015;54:3348-59 pubmed publisher
    We have investigated how the natural LCAT[T147I] and LCAT[P274S] mutations affect the pathway of biogenesis of HDL. Gene transfer of WT LCAT in LCAT(-/-) mice increased 11...
  29. Thacker S, Rousset X, Esmail S, Zarzour A, Jin X, Collins H, et al. Increased plasma cholesterol esterification by LCAT reduces diet-induced atherosclerosis in SR-BI knockout mice. J Lipid Res. 2015;56:1282-95 pubmed publisher
    b>LCAT, a plasma enzyme that esterifies cholesterol, has been proposed to play an antiatherogenic role, but animal and epidemiologic studies have yielded conflicting results...
  30. Tanigawa H, Billheimer J, Tohyama J, Fuki I, Ng D, Rothblat G, et al. Lecithin: cholesterol acyltransferase expression has minimal effects on macrophage reverse cholesterol transport in vivo. Circulation. 2009;120:160-9 pubmed publisher
    Lecithin:cholesterol acyltransferase (LCAT) catalyzes the formation of plasma cholesteryl ester, plays a key role in high-density lipoprotein metabolism, and has been believed to be critical in the process of reverse cholesterol transport ..
  31. Peelman F, Vanloo B, Verschelde J, Labeur C, Caster H, Taveirne J, et al. Effect of mutations of N- and C-terminal charged residues on the activity of LCAT. J Lipid Res. 2001;42:471-9 pubmed
    On the basis of structural homology calculations, we previously showed that lecithin:cholesterol acyltransferase (LCAT), like lipases, belongs to the alpha/beta hydrolase fold family...
  32. Sakai N, Vaisman B, Koch C, Hoyt R, Meyn S, Talley G, et al. Targeted disruption of the mouse lecithin:cholesterol acyltransferase (LCAT) gene. Generation of a new animal model for human LCAT deficiency. J Biol Chem. 1997;272:7506-10 pubmed
    We have established a mouse model for human LCAT deficiency by performing targeted disruption of the LCAT gene in mouse embryonic stem cells. Homozygous LCAT-deficient mice were healthy at birth and fertile...
  33. Alam K, Meidell R, Spady D. Effect of up-regulating individual steps in the reverse cholesterol transport pathway on reverse cholesterol transport in normolipidemic mice. J Biol Chem. 2001;276:15641-9 pubmed
    ..Overexpression of 7alpha-hydroxylase, Scavenger receptor B1, lecithin:cholesterol acyltransferase (LCAT), or apoA-I in the liver did not stimulate cholesterol efflux from any extrahepatic tissue...
  34. Furbee J, Francone O, Parks J. Alteration of plasma HDL cholesteryl ester composition with transgenic expression of a point mutation (E149A) of human LCAT. J Lipid Res. 2001;42:1626-35 pubmed
    We have previously identified a single amino acid mutation (hE149A) in human LCAT that increases its in vitro reactivity with phosphatidylcholine species containing sn-2 arachidonate (Wang et al. 1997. J. Biol. Chem. 272: 280-286)...
  35. Ng D, Maguire G, Wylie J, Ravandi A, Xuan W, Ahmed Z, et al. Oxidative stress is markedly elevated in lecithin:cholesterol acyltransferase-deficient mice and is paradoxically reversed in the apolipoprotein E knockout background in association with a reduction in atherosclerosis. J Biol Chem. 2002;277:11715-20 pubmed
    Complete lecithin:cholesterol acyltransferase (LCAT) deficiency is a rare cause of severe hypoalphalipoproteinemia, but the affected subjects are surprisingly not particularly prone to premature coronary heart disease...
  36. Li L, Hossain M, Sadat S, Hager L, Liu L, Tam L, et al. Lecithin cholesterol acyltransferase null mice are protected from diet-induced obesity and insulin resistance in a gender-specific manner through multiple pathways. J Biol Chem. 2011;286:17809-20 pubmed publisher
    Complete lecithin cholesterol acyltransferase (LCAT) deficiency uniformly results in a profound HDL deficiency...
  37. Hossain M, Tsujita M, Akita N, Kobayashi F, Yokoyama S. Cholesterol homeostasis in ABCA1/LCAT double-deficient mouse. Biochim Biophys Acta. 2009;1791:1197-205 pubmed publisher
    ..in mice with the two major cholesterol transport pathways for catabolism interrupted by disrupting abca1, lcat, or both. Plasma HDL markedly decreased in these genotype but LDL/VLDL decreased only in the double deficiency...
  38. Li L, Naples M, Song H, Yuan R, Ye F, Shafi S, et al. LCAT-null mice develop improved hepatic insulin sensitivity through altered regulation of transcription factors and suppressors of cytokine signaling. Am J Physiol Endocrinol Metab. 2007;293:E587-94 pubmed
    We previously reported that LCAT-deficient mice develop not only low HDL-cholesterol but also hypertriglyceridemia, hepatic triglyceride (TG) overproduction, and, unexpectedly, improved hepatic insulin sensitivity and reduced hepatic TG ..
  39. Chroni A, Duka A, Kan H, Liu T, Zannis V. Point mutations in apolipoprotein A-I mimic the phenotype observed in patients with classical lecithin:cholesterol acyltransferase deficiency. Biochemistry. 2005;44:14353-66 pubmed
    ..around the kinks flanking helices 4 and 6 of apoA-I and of the deletion of helix 6 on the in vivo activity of LCAT and the biogenesis of HDL...
  40. Ng D, Xie C, Maguire G, Zhu X, Ugwu F, Lam E, et al. Hypertriglyceridemia in lecithin-cholesterol acyltransferase-deficient mice is associated with hepatic overproduction of triglycerides, increased lipogenesis, and improved glucose tolerance. J Biol Chem. 2004;279:7636-42 pubmed
    ..We investigated the mechanism of HTG in the ldlr-/- x lcat-/- (double knockout (dko)) mice using the ldlr-/- x lcat+/+ (knock-out (ko)) littermates as control...
  41. Parks J, Li H, Gebre A, Smith T, Maeda N. Effect of apolipoprotein A-I deficiency on lecithin:cholesterol acyltransferase activation in mouse plasma. J Lipid Res. 1995;36:349-55 pubmed
    Plasma cholesteryl ester (CE) synthesis by lecithin cholesterol acyltransferase (LCAT) is activated by apolipoprotein (apo)A-I...
  42. Scherer G, Bausch E, Gaa A, von Deimling O. Gene mapping on mouse chromosome 8 by interspecific crosses: new data on a linkage group conserved on human chromosome 16q. Genomics. 1989;5:275-82 pubmed
    ..16q, including the loci for chymotrypsinogen B (Ctrb), haptoglobin (Hp), lecithin:cholesterol acyltransferase (Lcat), metallothionein-1,-2 (Mt-1,-2), tyrosine aminotransferase (Tat), and uvomorulin (Um)...
  43. Tlili A, Noll C, Middendorp S, Duchon A, Jouan M, Benabou E, et al. DYRK1A overexpression decreases plasma lecithin:cholesterol acyltransferase activity and apolipoprotein A-I levels. Mol Genet Metab. 2013;110:371-7 pubmed publisher
    ..We identified the role of DYRK1A overexpression on altered lipoprotein metabolism. ..
  44. Hoekstra M, Korporaal S, van der Sluis R, Hirsch Reinshagen V, Bochem A, Wellington C, et al. LCAT deficiency in mice is associated with a diminished adrenal glucocorticoid function. J Lipid Res. 2013;54:358-64 pubmed publisher
    ..Here we assessed adrenal glucocorticoid function in LCAT knockout (KO) mice to determine the specific contribution of HDL-cholesteryl esters to adrenal glucocorticoid ..
  45. Hirsch Reinshagen V, Donkin J, Stukas S, Chan J, Wilkinson A, Fan J, et al. LCAT synthesized by primary astrocytes esterifies cholesterol on glia-derived lipoproteins. J Lipid Res. 2009;50:885-93 pubmed publisher
    ..However, brain lipid metabolism is not completely understood. In plasma, LCAT catalyses the esterification of free cholesterol on circulating lipoproteins, a key step in the maturation of HDL...
  46. Zhu X, Herzenberg A, Eskandarian M, Maguire G, Scholey J, Connelly P, et al. A novel in vivo lecithin-cholesterol acyltransferase (LCAT)-deficient mouse expressing predominantly LpX is associated with spontaneous glomerulopathy. Am J Pathol. 2004;165:1269-78 pubmed
    Complete lecithin cholesterol acyltransferase (LCAT) deficiency is a rare genetic cause of extreme reduction in high density lipoproteins and there is a high prevalence of chronic renal dysfunction that may progress to renal failure...