J Clin Lipidol 2018 Mar 9. Epub 2018 Mar 9.

Guy's, St Thomas' and Lewisham and Greenwich Trust, St. Thomas' Hospital, London, United Kingdom.

We report the case of a 39-year-old West African man in whom high-density lipoprotein cholesterol (HDL-C) was identified as undetectable at <0.08 mmol/L. Total cholesterol in the same sample was 2. Read More

Metabolism 2018 Mar 8. Epub 2018 Mar 8.

Institute of Cardiovascular Sciences and Key Laboratory of Molecular Cardiovascular Sciences, Ministry of Education, Peking University, Beijing 100191, China,. Electronic address:

Objective: Lecithin cholesterol acyltransferase (LCAT) plays a pivotal role in HDL metabolism but its influence on atherosclerosis remains controversial for decades both in animal and clinical studies. Because lack of cholesteryl ester transfer protein (CETP) is a major difference between murine and humans in lipoprotein metabolism, we aimed to create a novel Syrian Golden hamster model deficient in LCAT activity, which expresses endogenous CETP, to explore its metabolic features and particularly the influence of LCAT on the development of atherosclerosis.

Methods: CRISPIR/CAS9 gene editing system was employed to generate mutant LCAT hamsters. Read More

Chem Pharm Bull (Tokyo) 2018 ;66(3):217-224

Clinical Cell Biology and Medicine, Chiba University Graduate School of Medicine, Chiba University.

Despite the critical need for lifelong treatment of inherited and genetic diseases, there are no developmental efforts for most such diseases due to their rarity. Recent progress in gene therapy, including the approvals of two products (Glybera and Strimvelis) that may provide patients with sustained effects, has shed light on the development of gene therapy products. Most gene therapy products are based on either adeno-associated virus-mediated in vivo gene transfer to target tissues or administration of ex vivo gene-transduced hematopoietic cells. Read More

J Assoc Physicians India 2017 Oct;65(10):90-91

Professor, Department of Nephrology, Madras Medical College and Rajiv Gandhi Government General Hospital, Chennai, Tamil Nadu.

Familial lecithin-cholesterol acyltransferase (LCAT) deficiency is a rare autosomal recessive (AR) disease caused by mutation in the LCAT gene. LCAT enzyme esterifies cholesterol molecules in high-density lipoprotein(HDL) and low density-lipoprotein (LDL) particles. This enzyme deficiency is characterised by progressive corneal opacification, glomerulopathy, mild - moderate haemolytic anaemia and very low plasma levels of HDL. Read More

JIMD Rep 2017 Oct 6. Epub 2017 Oct 6.

I3S - Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Rua Alfredo Allen 208, 4200-135, Oporto, Portugal.

Familial lecithin-cholesterol acyltransferase deficiency (FLD) is a rare recessive disorder of cholesterol metabolism, caused by loss-of-function mutations in the human LCAT gene, leading to alterations in the lipid/lipoprotein profile, with extremely low HDL levels.The classical FLD phenotype is characterized by diffuse corneal opacification, haemolytic anaemia and proteinuric chronic kidney disease (CKD); an incomplete form, only affecting the corneas, has been reported in a few families worldwide.We describe an intermediate phenotype of LCAT deficiency, with CKD preceding the development of corneal clouding, in two Portuguese brothers apparently homozygous for a novel missense LCAT gene mutation. Read More

J Clin Biochem Nutr 2017 Sep 28;61(2):108-117. Epub 2017 Jul 28.

School of Bioscience and Biotechnology, Tokyo University of Technology, 1404-1 Katakura-cho, Hachioji, Tokyo 192-0982, Japan.

Patients with post-cardiac arrest syndrome (PCAS) suffer from whole body ischemia/reperfusion injury similar to that experienced by newborn babies. Increased oxidative stress was confirmed in PCAS patients ( = 40) at the time of hospitalization by a significant increase in the percentage of the oxidized form of coenzyme Q10 in total coenzyme Q10 compared to age-matched healthy controls ( = 55). Tissue oxidative damage in patients was suggested by the significant increase in plasma levels of free fatty acids (FFA) and the significant decrease in polyunsaturated fatty acid contents in total FFA. Read More

J Clin Lipidol 2017 Nov - Dec;11(6):1475-1479.e3. Epub 2017 Aug 24.

Departamento de Medicina Interna, Servicio de Medicina Interna, Hospital Universitario de Guadalajara, Servicio de Salud de Castilla La Mancha, Guadalajara, Castilla la Mancha, Spain; Departamento de Medicina, Universidad de Alcalá, Madrid, Spain.

A patient from Romania with extraordinarily high total cholesterol levels and clinical and biochemical features consistent with familial lecithin-cholesterol acyltransferase deficiency is reported. The genetic analysis performed on our proband showed a novel homozygous mutation on codon 119 of lecithin-cholesterol acyltransferase gene that causes the substitution of glycine by aspartate. The same mutation, also in homozygosis, was observed in her older sister, whereas his brother presented it in heterozygosis. Read More

Ann Clin Biochem 2017 Jan 1:4563217733285. Epub 2017 Jan 1.

1 Lipoprotein Metabolism Section, Cardio-Pulmonary Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD, USA.

Background Lecithin:cholesterol acyltransferase (LCAT) is a plasma enzyme that esterifies cholesterol. Recombinant human LCAT (rhLCAT) is now being developed as an enzyme replacement therapy for familial LCAT deficiency and as a possible treatment for acute coronary syndrome. The current 'gold standard' assay for LCAT activity involves the use of radioisotopes, thus making it difficult for routine clinical use. Read More

Am J Kidney Dis 2017 Jul;70(1):e5-e6

Department of Pathology, Microbiology and Immunology, Vanderbilt University, Nashville, TN. Electronic address:

J Pharmacol Exp Ther 2017 Aug 2;362(2):306-318. Epub 2017 Jun 2.

Lipid Metabolism Section, Cardiovascular and Pulmonary Branch (L.A.F., S.J.D., S.M.G., B.L.V., R.D.S., A.T.R.), Systems Biology Center (A.A., M.G.), and Laboratory of Biochemistry (R.L.L.), National Institutes of Health National Heart, Lung, and Blood Institute, Bethesda, Maryland; Department of Chemistry, American University, Washington, DC (M.K., R.K.); University of Milano, Milano, Italy (A.F.O., L.C.); Department of Chemistry, Vanderbilt University, Nashville, Tennessee (R.F.K.); Departments of Pharmacology and Biological Chemistry, Life Sciences Institute, University of Michigan, Ann Arbor, Michigan (K.A.M., J.J.G.T.); and National Institutes of Health National Center for Advancing Translational Sciences, Bethesda, Maryland (M.S., A.J.)

Lecithin:cholesterol acyltransferase (LCAT) catalyzes plasma cholesteryl ester formation and is defective in familial lecithin:cholesterol acyltransferase deficiency (FLD), an autosomal recessive disorder characterized by low high-density lipoprotein, anemia, and renal disease. This study aimed to investigate the mechanism by which compound A [3-(5-(ethylthio)-1,3,4-thiadiazol-2-ylthio)pyrazine-2-carbonitrile], a small heterocyclic amine, activates LCAT. The effect of compound A on LCAT was tested in human plasma and with recombinant LCAT. Read More

CEN Case Rep 2016 Nov 7;5(2):192-196. Epub 2016 Jun 7.

Department of Clinical-Laboratory and Experimental-Research Medicine, Toho University Sakura Medical Center, Sakura, Chiba, 285-8741, Japan.

Familial lecithin:cholesterol acyltransferase (LCAT) deficiency is a rare inherited disorder that causes an extremely low high-density lipoprotein cholesterol concentration in serum. Recently, acquired LCAT deficiency caused by IgG antibodies to LCAT, without any LCAT gene mutation, was reported. Here we describe a case of acquired LCAT deficiency occurring in association with sarcoidosis. Read More

Exp Biol Med (Maywood) 2017 Jan 1:1535370217706966. Epub 2017 Jan 1.

Children's Hospital Oakland Research Institute, Oakland, CA 94609, USA.

In sickle cell disease (SCD), alterations of cholesterol metabolism is in part related to abnormal levels and activity of plasma proteins such as lecithin cholesterol acyltransferase (LCAT), and apolipoprotein A-I (ApoA-I). In addition, the size distribution of ApoA-I high density lipoproteins (HDL) differs from normal blood. The ratio of the amount of HDL particle relative to the smaller higher density pre-β HDL (HDL) particle was shifted toward HDL. Read More

J Lipid Res 2017 May 28;58(5):994-1001. Epub 2017 Mar 28.

Centro E. Grossi Paoletti, Dipartimento di Scienze Farmacologiche e Biomolecolari Università degli Studi di Milano, Milano, Italy

The aim of this study was to evaluate the vasoprotective effects of HDL isolated from carriers of LCAT deficiency, which are characterized by a selective depletion of LpA-I:A-II particles and predominance of preβ migrating HDL. HDLs were isolated from LCAT-deficient carriers and tested in vitro for their capacity to promote NO production and to inhibit vascular cell adhesion molecule-1 (VCAM-1) expression in cultured endothelial cells. HDLs from carriers were more effective than control HDLs in promoting eNOS activation with a gene-dose-dependent effect ( = 0. Read More

PLoS One 2017 20;12(1):e0169939. Epub 2017 Jan 20.

Department of Medicine, University of California San Diego, La Jolla, California, United States of America.

Hypertriglyceridemia is an independent risk factor for cardiovascular disease. Apolipoprotein C-II (APOC2) is an obligatory cofactor for lipoprotein lipase (LPL), the major enzyme catalyzing plasma triglyceride hydrolysis. We have created an apoc2 knockout zebrafish model, which mimics the familial chylomicronemia syndrome (FCS) in human patients with a defect in the APOC2 or LPL gene. Read More

G Ital Nefrol 2016 Malattie Metaboliche e Rene;33(S68)

Lipidoses occur for an abnormal storage parenchymal deposition of lipids and products of their metabolism in large amounts or sometimes, involving only some particular tissue structures. The lipid storage is usually due to an inborn error causing an enzyme absence /deficiency in the primary lipidoses and to a complex metabolism alterations in the secondary forms. However, histologically all lipid depositions look very similar, and immunohistochemical investigation, clinical pictures knowledge and genetic tests need to make a correct diagnosis. Read More

G Ital Nefrol 2016 Malattie Metaboliche e Rene;33(S68)

LCAT synthesizes most of the plasma cholesteryl esters, and plays a major role in HDL metabolism. Mutations in the LCAT gene cause two syndromes, familial LCAT deficiency (FLD) and fish-eye disease (FED), both characterized by severe alterations in plasma lipoprotein profile. Renal disease is the major cause of morbidity and mortality in FLD cases, but an established therapy is not currently available. Read More

J Assoc Physicians India 2016 Oct;64(10):90-91

Professor, Department of Nephrology, Madras Medical College and Rajiv Gandhi Government General Hospital, Chennai, Tamil Nadu.

Familial lecithin-cholesterol acyltransferase (LCAT) deficiency is a rare autosomal recessive (AR) disease caused by mutation in the LCAT gene. LCAT enzyme esterifies cholesterol molecules in high-density lipoprotein(HDL) and low density-lipoprotein (LDL) particles. This enzyme deficiency is characterised by progressive corneal opacification, glomerulopathy, mild - moderate haemolytic anaemia and very low plasma levels of HDL. Read More

Prog Cardiovasc Dis 2016 Sep - Oct;59(2):97-106. Epub 2016 Aug 24.

Cardiovascular Nutrition Laboratory, Human Nutrition Research Center on Aging at Tufts University and Tufts University School of Medicine, Boston, MA; Boston Heart Diagnostics, Framingham, MA.

Low serum high density lipoprotein cholesterol level (HDL-C) <40 mg/dL in men and <50 mg/dL in women is a significant independent risk factor for cardiovascular disease (CVD), and is often observed in patients with hypertriglyceridemia, obesity, insulin resistance, and diabetes. Patients with marked deficiency of HDL-C (<20 mg/dL) in the absence of secondary causes are much less common (<1% of the population). These patients may have homozygous, compound heterozygous, or heterozygous defects involving the apolipoprotein (APO)AI, ABCA1, or lecithin:cholesterol acyl transferase genes, associated with apo A-I deficiency, apoA-I variants, Tangier disease , familial lecithin:cholesteryl ester acyltransferase deficiency, and fish eye disease. Read More

Clin Transplant 2016 Oct 24;30(10):1370-1374. Epub 2016 Sep 24.

Department of Surgery, University of Maryland School of Medicine, Baltimore, MD, USA.

Background: Lecithin cholesterol acyl transferase (LCAT) deficiency is a rare autosomal recessive disorder of lipoprotein metabolism that results in end-stage renal disease (ESRD) necessitating transplantation. As LCAT is produced in the liver, combined kidney and liver transplantation was proposed to cure the clinical syndrome of LCAT deficiency.

Methods: A 29-year-old male with ESRD secondary to LCAT deficiency underwent a sequential kidney-liver transplantation from the same living donor (LD). Read More

J Clin Lipidol 2016 May-Jun;10(3):650-3. Epub 2015 Dec 23.

Pediatric Endocrinology and Diabetes, Cook Children's Medical Center, Fort Worth, TX.

Lipoprotein-X, which is composed of phospholipids and non-esterified cholesterol, is an abnormal lipoprotein with a density range similar to LDL-C. The two most common ways which lipoprotein-X accumulates is from reflux of bile salts into plasma or deficiency in lecithin cholesterol acyltransferase. This is a case of severe hypercholesterolemia and liver disease in a 3- year old male that presented with pruritus, pale stool, scleral ictus, and abdominal distention. Read More

Yakugaku Zasshi 2016 ;136(5):705-9

Chiba University Hospital Center for Advanced Medicine.

Although protein replacement is an effective treatment for serum protein deficiencies such as diabetes and hemophilia, recombinant protein products are not available for all rare inherited diseases due to the instability of the recombinant proteins and/or to cost. Gene therapy is the most attractive option for treating patients with such rare diseases. To develop an effective ex vivo gene therapy-based protein replacement treatment requires recipient cells that differ from those used in standard gene therapy, which is performed to correct the function of the recipient cells. Read More

Biochim Biophys Acta 2016 Jul 14;1861(7):594-605. Epub 2016 Apr 14.

Keenan Research Centre, Li Ka Shing Knowledge Institute, Department of Medicine, St Michael's Hospital, Toronto, Canada; Department of Physiology, Faculty of Medicine, University of Toronto, Toronto, Canada; Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Canada. Electronic address:

Non-alcoholic steatohepatitis (NASH), is the form of non-alcoholic fatty liver disease posing risk to progress into serious long term complications. Human and pre-clinical models implicate cellular cholesterol dysregulation playing important role in its development. Mouse model studies suggest synergism between dietary cholesterol and fat in contributing to NASH but the mechanisms remain poorly understood. Read More

J Clin Res Pediatr Endocrinol 2016 Sep 18;8(3):330-3. Epub 2016 Apr 18.

Uludağ University Faculty of Medicine, Department of Pediatrics, Division of Pediatric Metabolism and Endocrinology, Bursa, Turkey, E-mail:

Objective: Inherited metabolic diseases (IMDs) can affect many organ systems, including the endocrine system. There are limited data regarding endocrine dysfunctions related to IMDs in adults, however, no data exist in pediatric patients with IMDs. The aim of this study was to investigate endocrine dysfunctions in patients with IMDs by assessing their demographic, clinical, and laboratory data. Read More

J Clin Lipidol 2016 Mar-Apr;10(2):356-67. Epub 2015 Dec 23.

Cardiovascular and Pulmonary Branch, National Heart, Lung and Blood Institute, NIH, Bethesda, MD, USA.

Background: Humans with familial lecithin:cholesterol acyltransferase (LCAT) deficiency (FLD) have extremely low or undetectable high-density lipoprotein cholesterol (HDL-C) levels and by early adulthood develop many manifestations of the disorder, including corneal opacities, anemia, and renal disease.

Objective: To determine if infusions of recombinant human LCAT (rhLCAT) could reverse the anemia, halt progression of renal disease, and normalize HDL in FLD.

Methods: rhLCAT (ACP-501) was infused intravenously over 1 hour on 3 occasions in a dose optimization phase (0. Read More

Indian J Nephrol 2016 Jan-Feb;26(1):55-6

Department of Pathology, Apollo Hospital, Telangana, Hyderabad, India.

Nephrotic syndrome can be rarely due to inherited disorders of enzymes. One such variety is lecithin cholesterol acyltransferase deficiency. It leads to accumulation of unesterified cholesterol in the eye and other organs. Read More

PLoS One 2016 26;11(2):e0150083. Epub 2016 Feb 26.

Lipoprotein Metabolism Section, Cardiovascular and Pulmonary Branch, National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, Maryland, United States of America.

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. The aim of our study was to determine if LpX is nephrotoxic and to gain insight into the pathogenesis of FLD renal disease. We administered a synthetic LpX, nearly identical to endogenous LpX in its physical, chemical and biologic characteristics, to wild-type and Lcat-/- mice. Read More

J Nephropharmacol 2017 5;6(1):23-26. Epub 2016 Jan 5.

Department of Nephrology and Clinical Transplantation, Laboratory Medicine, Transfusion Services and Immunohematology, Institute of Kidney Diseases and Research Center, Dr. HL Trivedi Institute of Transplantation Sciences (IKDRC-ITS), Ahmedabad, India.

Clinical and biochemical manifestations of lecithin-cholesterol acyltransferase (LCAT) deficiency include an abnormal lipid profile (characterized by hypercholesterolemia with markedly decreased high-density lipoprotein cholesterol [HDL-C] and hypertriglyceridemia), corneal opacities, hematologic abnormalities (normochromic anemia of varying intensity), splenomegaly, variable early coronary artery disease and nephropathy (initially proteinuria followed by progressive deterioration of renal function). We presented a patient with nephrotic syndrome, which renal biopsy revealed classic features of LCAT deficiency. To our knowledge, the present case is the first reported case of LCAT deficiency presenting with symptoms related to nephrotic syndrome in a patient with no obvious family history without any corneal deposits and normal HDL-C levels. Read More

Nephrology (Carlton) 2016 Jan;21(1):73-4

Department of Nephrology, Monash Medical Centre, Clayton, Victoria, Australia.

Indian J Nephrol 2015 Nov-Dec;25(6):362-5

Department of Nephrology, PGIMER, Dr. Ram Manohar Lohia Hospital, New Delhi, India.

We report a family with a rare genetic disorder arising out of mutation in the gene that encodes for the enzyme lecithin-cholesterol acyltransferase (LCAT). The proband presented with nephrotic syndrome, hemolytic anemia, cloudy cornea, and dyslipidemia. Kidney biopsy showed certain characteristic features to suggest LCAT deficiency, and the enzyme activity in the serum was undetectable. Read More

Circ Res 2016 Jan 1;118(1):73-82. Epub 2015 Dec 1.

From the National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, MD (R.D.S., A.M.S., L.A.F., M.J.A., A.W., A.T.R.); AlphaCore Pharma LLC., Ann Arbor, MI (R.B.-A., B.A., B.R.K., R.H.); VascularStrategies LLC., Plymouth Meeting, PA (S.J.A., H.L.C.); and Department of Laboratory Medicine, Clinical Center, National Institutes of Health, Bethesda, MD (M.S.).

Rationale: Low high-density lipoprotein-cholesterol (HDL-C) in patients with coronary heart disease (CHD) may be caused by rate-limiting amounts of lecithin:cholesterol acyltransferase (LCAT). Raising LCAT may be beneficial for CHD, as well as for familial LCAT deficiency, a rare disorder of low HDL-C.

Objective: To determine safety and tolerability of recombinant human LCAT infusion in subjects with stable CHD and low HDL-C and its effect on plasma lipoproteins. Read More

J Atheroscler Thromb 2016 26;23(2):119-27. Epub 2015 Nov 26.

Centro Grossi Paoletti, Dipartimento di Scienze Farmacologiche e Biomolecolari, Università degli Studi di Milano.

Lecithin:cholesterol acyltransferase (LCAT) is the only enzyme capable of esterifying cholesterol in plasma, thus determining the maturation of high-density lipoproteins. Because it maintains an unesterified cholesterol gradient between peripheral cells and extracellular acceptors, for a long time, LCAT has been considered as a key enzyme in reverse cholesterol transport. However, despite the fact that it has been more than 50 years since the identification of LCAT, the role of this enzyme in the pathogenesis of atherosclerosis is still debated. Read More

Am J Kidney Dis 2016 Feb 19;67(2):329-36. Epub 2015 Nov 19.

Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN. Electronic address:

Numerous histiocytes are sometimes noted in glomeruli, giving rise to a foamy-appearing glomerulus. Foamy-appearing glomeruli may also be noted in conditions that do not contain numerous histiocytes. These disease entities are rare, have different underlying causes and pathophysiology, and can cause a diagnostic dilemma. Read More

Clin Chim Acta 2016 Feb 4;454:143-85. Epub 2015 Nov 4.

Department of Biochemistry, Worcester Royal Hospital, Worcester, United Kingdom.

Dyslipidemia is a commonly encountered clinical condition and is an important determinant of cardiovascular disease. Although secondary factors play a role in clinical expression, dyslipidemias have a strong genetic component. Familial hypercholesterolemia is usually due to loss-of-function mutations in LDLR, the gene coding for low density lipoprotein receptor and genes encoding for proteins that interact with the receptor: APOB, PCSK9 and LDLRAP1. Read More

J Biol Chem 2015 Dec 22;290(51):30514-29. Epub 2015 Oct 22.

From the Keenan Research Centre, Li Ka Shing Knowledge Institute, Department of Medicine, St. Michael's Hospital, Toronto, Ontario M5B 1W8, Canada and the Department of Physiology, Faculty of Medicine, and Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario M5S 1A8, Canada

Our laboratory previously reported that lecithin:cholesterol acyltransferase (LCAT) and LDL receptor double knock-out mice (Ldlr(-/-)xLcat(-/-) or DKO) spontaneously develop functioning ectopic brown adipose tissue (BAT) in skeletal muscle, putatively contributing to protection from the diet-induced obesity phenotype. Here we further investigated their developmental origin and the mechanistic role of LCAT deficiency. Gene profiling of skeletal muscle in DKO newborns and adults revealed a classical lineage. Read More

Clin Lipidol 2015 Aug;10(4):305-312

Department of Medicine, University of Chicago, Chicago, IL, 60637,USA ; Pritzker School of Medicine, University of Chicago, Chicago, IL 60637, USA ; Section of Endocrinology, Diabetes & Metabolism, University of Chicago, Chicago, IL, 60637,USA.

Lipoprotein X (LpX) is an abnormal lipoprotein found in conditions such as lecithin:cholesterol acyltransferase deficiency and cholestatic states (e.g., primary biliary cirrhosis and primary sclerosing cholangitis). Read More

Acta Biochim Pol 2015 28;62(3):621-3. Epub 2015 Aug 28.

Department of Internal Medicine and Cardiology, Medical University of Warsaw, Warsaw, Poland.

Hypercholesterolemia is a common disorder in adult population, but total cholesterol concentrations beyond 1000 mg/dl occur rarely, and are found in patients with homozygous familial hypercholesterolemia and familial lecithin-cholesterol acyltransferase deficiency, in chronic graft-versus-host disease of the liver, after intravenous infusion of fat emulsion (intralipid), in newborn infants with immature liver function, and in obstructive biliary cholestasis. Cholestasis induces a dramatic increase in plasma cholesterol and the appearance of an abnormal lipoprotein, lipoprotein X (LpX), in the plasma. We report a case of severe hypercholesterolemia mediated by LpX in a patient transplanted for primary biliary cirrhosis (PBC), who was qualified for liver re-transplantation (re-LTx) due to chronic cholestasis. Read More

Vascul Pharmacol 2015 Nov 5;74:114-121. Epub 2015 Aug 5.

Department of Pharmacological and Biomolecular Sciences, Università degli Studi di Milano, Milano, Italy. Electronic address:

Lecithin:cholesterol acyltransferase (LCAT) deficiency is associated with hypoalphalipoproteinemia, generally a predisposing factor for premature coronary heart disease. The evidence of accelerated atherosclerosis in LCAT-deficient subjects is however controversial. In this study, the effect of LCAT deficiency on vascular tone and endothelial function was investigated in LCAT knockout mice, which reproduce the human lipoprotein phenotype. Read More

Biochim Biophys Acta 2015 Oct 10;1852(10 Pt A):2106-15. Epub 2015 Jul 10.

Pharmacology Department, University of Patras Medical School, Rio Achaias TK. 26500, Greece. Electronic address:

HDL has important immunomodulatory properties, including the attenuation of lipopolysaccharide (LPS)-induced inflammatory response. As lecithin-cholesterol acyltransferase (LCAT) is a critical enzyme in the maturation of HDL we investigated whether LCAT-deficient (Lcat(-/-)) mice present an increased LPS-induced inflammatory response. LPS (100μg/kg body weight)-induced cytokine response in Lcat(-/-) mice was markedly enhanced and prolonged compared to wild-type mice. Read More

Cleve Clin J Med 2015 Jun;82(6):339-40

Professor of Medicine, Cleveland Clinic Lerner College of Medicine of Case Western University, Cleveland, OH, USA.

J Clin Lipidol 2015 May-Jun;9(3):390-5. Epub 2015 Mar 5.

Cardiovascular Nutrition Laboratory, Human Nutrition Research Center on Aging at Tufts University, Boston, MA, USA; Boston Heart Diagnostics, Framingham, MA, USA; Tufts University School of Medicine, Boston, MA, USA. Electronic address:

We report a novel heterozygous apolipoprotein A-I (apoA-I) missense mutation (c.517C>A, p.Arg149Ser, designated as apoA-IBoston) in a 67-year-old woman and her 2 sons, who had mean serum high-density lipoprotein (HDL) cholesterol, apoA-I, and apoA-I in very large α-1 HDL that were 10%, 35%, and 16% of normal, respectively (all P < . Read More

PLoS One 2015 2;10(6):e0121956. Epub 2015 Jun 2.

Veterinary Physiology, Vetsuisse Faculty University of Bern, Bern, Switzerland.

The response of cholesterol metabolism to a negative energy balance (NEB) induced by feed restriction for 3 weeks starting at 100 days in milk (DIM) compared to the physiologically occurring NEB in week 1 postpartum (p.p.) was investigated in 50 dairy cows (25 control (CON) and 25 feed-restricted (RES)). Read More

J Lipid Res 2015 Jul 11;56(7):1282-95. Epub 2015 May 11.

Lipoprotein Metabolism Section, Cardiovascular-Pulmonary Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892.

LCAT, a plasma enzyme that esterifies cholesterol, has been proposed to play an antiatherogenic role, but animal and epidemiologic studies have yielded conflicting results. To gain insight into LCAT and the role of free cholesterol (FC) in atherosclerosis, we examined the effect of LCAT over- and underexpression in diet-induced atherosclerosis in scavenger receptor class B member I-deficient [Scarab(-/-)] mice, which have a secondary defect in cholesterol esterification. Scarab(-/-)×LCAT-null [Lcat(-/-)] mice had a decrease in HDL-cholesterol and a high plasma ratio of FC/total cholesterol (TC) (0. Read More

Nat Commun 2015 Mar 2;6:6250. Epub 2015 Mar 2.

Life Sciences Institute and the Departments of Pharmacology and Biological Chemistry, University of Michigan, Ann Arbor, Michigan 48109, USA.

Lysosomal phospholipase A2 (LPLA2) and lecithin:cholesterol acyltransferase (LCAT) belong to a structurally uncharacterized family of key lipid-metabolizing enzymes responsible for lung surfactant catabolism and for reverse cholesterol transport, respectively. Whereas LPLA2 is predicted to underlie the development of drug-induced phospholipidosis, somatic mutations in LCAT cause fish eye disease and familial LCAT deficiency. Here we describe several high-resolution crystal structures of human LPLA2 and a low-resolution structure of LCAT that confirms its close structural relationship to LPLA2. Read More

J Nephropathol 2015 Jan 1;4(1):25-8. Epub 2015 Jan 1.

Department of Pathology and Laboratory Medicine, King Faisal Specialist Hospital and Research Center, Riyadh, Kingdom of Saudi Arabia.

Background: Lecithin cholesterol acyltransferase (LCAT) is an important enzyme in cholesterol metabolism that is involved in the esterification of cholesterol. A lack of this enzyme results in deranged metabolic pathways that are not completely understood, resulting in abnormal deposition of lipids in several organs. Clinically, it manifests with proteinuria, dyslipidemia and corneal opacity with progressive chronic kidney disease resulting in end-stage renal disease. Read More

Arch Biochem Biophys 2015 Apr 17;572:11-18. Epub 2015 Jan 17.

Department of Food Science and Rutgers Center for Lipid Research, Rutgers University, New Brunswick, NJ 08091, USA. Electronic address:

In mammals, β-carotene-15,15'-oxygenase (BCO1) is the main enzyme that cleaves β-carotene, the most abundant vitamin A precursor, to generate retinoids (vitamin A derivatives), both in adult and developing tissues. We previously reported that, in addition to this function, BCO1 can also influence the synthesis of retinyl esters, the storage form of retinoids, in the mouse embryo at mid-gestation. Indeed, lack of embryonic BCO1 impaired both lecithin-dependent and acyl CoA-dependent retinol esterification, mediated by lecithin:retinol acyltransferase (LRAT) and acyl CoA:retinol acyltransferase (ARAT), respectively. Read More

J Lipid Res 2015 Mar 14;56(3):620-34. Epub 2015 Jan 14.

Center for Computational and Structural Dynamics University of Alabama at Birmingham, Birmingham, AL 35294-0012 Department of Medicine, University of Alabama at Birmingham, Birmingham, AL 35294-0012.

LCAT is activated by apoA-I to form cholesteryl ester. We combined two structures, phospholipase A2 (PLA2) that hydrolyzes the ester bond at the sn-2 position of oxidized (short) acyl chains of phospholipid, and bacteriophage tubulin PhuZ, as C- and N-terminal templates, respectively, to create a novel homology model for human LCAT. The juxtaposition of multiple structural motifs matching experimental data is compelling evidence for the general correctness of many features of the model: i) The N-terminal 10 residues of the model, required for LCAT activity, extend the hydrophobic binding trough for the sn-2 chain 15-20 Å relative to PLA2. Read More

Kidney Int 2015 Jun 7;87(6):1223-9. Epub 2015 Jan 7.

Division of Nephrology and Dialysis, Department of Medical and Surgical Specialties, Radiological Sciences, and Public Health, University of Brescia and Montichiari Hospital, Brescia, Italy.

Apolipoprotein A-I is the main protein of high-density lipoprotein particles, and is encoded by the APOA1 gene. Several APOA1 mutations have been found, either affecting the lecithin:cholesterol acyltransferase activity, determining familial HDL deficiency, or resulting in amyloid formation with prevalent deposits in the kidney and liver. Evaluation of familial tubulointerstitial nephritis in patients with the Leu75Pro APOA-I amyloidosis mutation resulted in the identification of 253 carriers belonging to 50 families from Brescia, Italy. Read More

PLoS One 2014 30;9(12):e115744. Epub 2014 Dec 30.

The City College of New York, Biology Department, New York, New York, United States of America.

Objective: Plasma apolipoprotein (apo)D, a ubiquitously expressed protein that binds small hydrophobic ligands, is found mainly on HDL particles. According to studies of human genetics and lipid disorders, plasma apoD levels positively correlate with HDL-cholesterol and apoAI levels. Thus, we tested the hypothesis that apoD was a regulator of HDL metabolism. Read More

Handb Exp Pharmacol 2015 ;224:301-36

Division of Biopharmaceutics, Gorlaeus Laboratories, Leiden Academic Centre for Drug Research, Leiden University, Einsteinweg 55, 2333CC, Leiden, The Netherlands,

High-density lipoprotein (HDL) is considered to be an anti-atherogenic lipoprotein moiety. Generation of genetically modified (total body and tissue-specific knockout) mouse models has significantly contributed to our understanding of HDL function. Here we will review data from knockout mouse studies on the importance of HDL's major alipoprotein apoA-I, the ABC transporters A1 and G1, lecithin:cholesterol acyltransferase, phospholipid transfer protein, and scavenger receptor BI for HDL's metabolism and its protection against atherosclerosis in mice. Read More