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Lipids 2022 May 23;57(3):183-195. Epub 2022 Mar 23.

Lipid Pathobiochemistry Group, German Cancer Research Center, Heidelberg, Germany.

1-O-Acylceramides (1-OACs) have a fatty acid esterified to the 1-hydroxyl of the sphingosine head group of the ceramide, and recently we identified these lipids as natural components of human and mouse epidermis. Here we show epidermal 1-OACs arise shortly before birth during the establishment of the water permeability barrier in mice. Fractionation of human epidermis indicates 1-OACs concentrate in the stratum corneum. Read More

Mol Genet Metab Rep 2022 Mar 3;30:100840. Epub 2022 Jan 3.

Laboratory of Immunogenetics and Molecular Biology, Federal University of Piauí, Teresina, Brazil, Campus Ministro Petrônio Portella - SG 16. Bairro Ininga, Teresina, Piauí 64049-550, Brazil.

Lecithin-cholesterol acyltransferase (LCAT), an enzyme that participates in lipoprotein metabolism, plays an important role in cholesterol homeostasis. Mutations in the gene can cause two rare genetic disorders: familial LCAT deficiency (FLD), which is characterized by corneal opacities, normocytic anemia, dyslipidemia, and proteinuria progressing to chronic renal failure, and fish-eye disease (FED), which causes dyslipidemia and progressive corneal opacities. Herein, we report six suspected cases of FLD in the backlands of Piauí, located in northeast Brazil. Read More

Biomed Pharmacother 2022 Mar 2;147:112677. Epub 2022 Feb 2.

Institute of Digestive Disease, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200032, China. Electronic address:

Lecithin: cholesterol acyltransferase (LCAT) is the only enzyme in plasma which is able to esterify cholesterol and boost cholesterol esterify with phospholipid-derived acyl chains. In order to better understand the progress of LCAT research, it is always inescapable that it is linked to high-density lipoprotein (HDL) metabolism and reverse cholesterol transport (RCT). Because LCAT plays a central role in HDL metabolism and RCT, many animal studies and clinical studies are currently aimed at improving plasma lipid metabolism by increasing LCAT activity in order to find better treatment options for familial LCAT deficiency (FLD), fish eye disease (FED), and cardiovascular disease. Read More

J Lipid Res 2022 Mar 20;63(3):100169. Epub 2022 Jan 20.

Division of Translational Medicine and Human Genetics, Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA. Electronic address:

Syndromes associated with LCAT deficiency, a rare autosomal recessive condition, include fish-eye disease (FED) and familial LCAT deficiency (FLD). FLD is more severe and characterized by early and progressive chronic kidney disease (CKD). No treatment is currently available for FLD, but novel therapeutics are under development. Read More

Acta Clin Belg 2021 Nov 18:1-6. Epub 2021 Nov 18.

Miguel Servet Ophthalmology Research Group (GIMSO), Aragón Institute for Health Research (Iis-aragón), Zaragoza, Spain.

Background: Fish-eye disease (FED) is due to a partial deficiency in LCAT activity. Nevertheless, Familial lecithin-cholesterol acyltransferase deficiency (FLD), also called Norum disease, appears when the deficiency is complete. They are both rare genetic disorders inherited in an autosomal recessive manner. Read More

J Intern Med 2022 03 11;291(3):364-370. Epub 2021 Nov 11.

Unit of Nephrology, Dialysis and Renal Transplantation, S. Maria della Misericordia Hospital, Azienda Sanitaria Universitaria Friuli Centrale (ASUFC), Udine, Italy.

Background: Kidney failure is the major cause of morbidity and mortality in familial lecithin:cholesterol acyltransferase deficiency (FLD), a rare inherited lipid disorder with no cure. Lipoprotein X (LpX), an abnormal lipoprotein, is primarily accountable for nephrotoxicity.

Methods: CER-001 was tested in an FLD patient with dramatic kidney disease for 12 weeks. Read More

J Atheroscler Thromb 2021 Oct 22. Epub 2021 Oct 22.

Division of Endocrinology and Metabolism, Department of Internal Medicine, School of Medicine, Jichi Medical University.

Introduction: Primary dyslipidemias are inherited disorders in plasma lipoprotein metabolism that lead to serious cardiovascular and other complications. The Japanese Ministry of Health, Labor and Welfare (MHLW) covers medical expenses, under the Research Program on Rare and Intractable Diseases, for homozygous familial hypercholesterolemia (FH), familial chylomicronemia, sitosterolemia, cerebrotendinous xanthomatosis, lecithin:cholesterol acyltransferase deficiency, Tangier disease, and abetalipoproteinemia. Apolipoprotein A1 deficiency, heterozygous FH, and type III hyperlipoproteinemia are covered by the MHLW Pediatric Chronic Disease Program. Read More

Obstet Med 2021 Sep 9;14(3):193-196. Epub 2020 Sep 9.

Tecnologico de Monterrey, Escuela de Medicina y Ciencias de la Salud, Monterrey, Nuevo Leon, Mexico.

Lecithin-cholesterol acyltransferase (LCAT) deficiency is a rare autosomal recessive condition affecting lipid metabolism with a prevalence of less than 1:1,000,000. Described here is the case of a 29-year-old pregnant woman with a diagnosis of LCAT deficiency (c.140G>A in exon 4), who had three episodes of hypertriglyceridemia-induced pancreatitis and nephrotic-range proteinuria throughout the pregnancy. Read More

Am J Ophthalmol Case Rep 2021 Dec 21;24:101211. Epub 2021 Sep 21.

National Health Insurance Sakashita Hospital, 722-1, Sakashita, Nakatsugawa, Gifu, Japan.

Purpose: We report our findings of a patient with a definitive diagnosis of familial lecithin-cholesterol acyltransferase deficiency (FLD), whose corneal thickness was measured using swept-source optical coherence tomography (OCT) and who underwent an ophthalmologic therapeutic intervention.

Observations: The patient was a 78-year-old Japanese man diagnosed with FLD at the age of 52 years. This was his first ever visit to an ophthalmology clinic. Read More

Lipids Health Dis 2021 Jul 13;20(1):70. Epub 2021 Jul 13.

Department of Endocrinology and Metabolism, Instituto Nacional de Ciencias Médicas y Nutrición, Salvador Zubirán, Av. Vasco de Quiroga 15, Belisario Domínguez Secc. 16, , Tlalpan, 14080, México City, México.

Background: LCAT (lecithin-cholesterol acyltransferase) deficiency is characterized by two distinct phenotypes, familial LCAT deficiency (FLD) and Fish Eye disease (FED). This is the first systematic review evaluating the ethnic distribution of LCAT deficiency, with particular emphasis on Latin America and the discussion of three Mexican-Mestizo probands.

Methods: A systematic review was conducted following the PRISMA (Preferred Reporting Items for Systematic review and Meta-Analysis) Statement in Pubmed and SciELO. Read More

Diabetologia 2021 09 13;64(9):1917-1926. Epub 2021 Jul 13.

Pharmacology Laboratory, Department of Medicine, School of Health Sciences, University of Patras, Rio Achaias, Greece.

HDL is a complex macromolecular cluster of various components, such as apolipoproteins, enzymes and lipids. Quality evidence from clinical and epidemiological studies led to the principle that HDL-cholesterol (HDL-C) levels are inversely correlated with the risk of CHD. Nevertheless, the failure of many cholesteryl ester transfer protein inhibitors to protect against CVD casts doubts on this principle and highlights the fact that HDL functionality, as dictated by its proteome and lipidome, also plays an important role in protecting against metabolic disorders. Read More

Front Res Metr Anal 2021 25;6:644728. Epub 2021 Jun 25.

Department of Computer Science, Virginia Commonwealth University, Richmond, VA, United States.

In this paper, we describe how we applied LBD techniques to discover lecithin cholesterol acyltransferase (LCAT) as a druggable target for cardiac arrest. We fully describe our process which includes the use of high-throughput metabolomic analysis to identify metabolites significantly related to cardiac arrest, and how we used LBD to gain insights into how these metabolites relate to cardiac arrest. These insights lead to our proposal (for the first time) of LCAT as a druggable target; the effects of which are supported by studies which were brought forth by this work. Read More

Biochim Biophys Acta Mol Cell Biol Lipids 2021 10 29;1866(10):159002. Epub 2021 Jun 29.

Department of Medicine, University of Illinois, Chicago, IL 60612, USA; Jesse Brown VA Medical Center, Chicago, IL 60612, USA. Electronic address:

DHA (docosahexaenoic acid) is an essential fatty acid that is required for the normal development and function of the brain. Because of its inability to synthesize adequate amounts of DHA from the precursors, the brain has to acquire DHA from plasma through the blood brain barrier (BBB). Recent studies demonstrated the presence of a transporter at the BBB that specifically transports DHA into the brain in the form of lysophosphatidylcholine (LPC-DHA). Read More

Arterioscler Thromb Vasc Biol 2021 07 13;41(7):2141-2148. Epub 2021 May 13.

Institute of Cardiovascular Sciences and Key Laboratory of Molecular Cardiovascular Sciences, Ministry of Education, School of Basic Medical Sciences, Peking University, Beijing, China (M.G., W.H., Y.W., G.L., X.X.).

[Figure: see text]. Read More

J Atheroscler Thromb 2021 Jul 18;28(7):679-691. Epub 2021 Apr 18.

Department of Molecular Pathogenesis, National Cerebral and Cardiovascular Center Research Institute.

Lecithin cholesterol acyltransferase (LCAT) is a lipid-modification enzyme that catalyzes the transfer of the acyl chain from the second position of lecithin to the hydroxyl group of cholesterol (FC) on plasma lipoproteins to form cholesteryl acylester and lysolecithin. Familial LCAT deficiency is an intractable autosomal recessive disorder caused by inherited dysfunction of the LCAT enzyme. The disease appears in two different phenotypes depending on the position of the gene mutation: familial LCAT deficiency (FLD, OMIM 245900) that lacks esterification activity on both HDL and ApoB-containing lipoproteins, and fish-eye disease (FED, OMIM 136120) that lacks activity only on HDL. Read More

Cells 2021 03 31;10(4). Epub 2021 Mar 31.

Centro E. Grossi Paoletti, Dipartimento di Scienze Farmacologiche e Biomolecolari, Università degli Studi di Milano, 20133 Milano, Italy.

Dyslipidemia is a typical trait of patients with chronic kidney disease (CKD) and it is typically characterized by reduced high-density lipoprotein (HDL)-cholesterol(c) levels. The low HDL-c concentration is the only lipid alteration associated with the progression of renal disease in mild-to-moderate CKD patients. Plasma HDL levels are not only reduced but also characterized by alterations in composition and structure, which are responsible for the loss of atheroprotective functions, like the ability to promote cholesterol efflux from peripheral cells and antioxidant and anti-inflammatory proprieties. Read More

Ann Intern Med 2021 07 2;174(7):1022-1025. Epub 2021 Mar 2.

Institut National de la Science et de la Recherche Médicale, INSERM U1297-Institut des Maladies Métaboliques et Cardiovasculaires, and Université Paul Sabatier-Toulouse III, Toulouse, France.

J Lipid Res 2021 10;62:100006. Epub 2020 Dec 10.

Dipartimento di Scienze Farmacologiche e Biomolecolari & DSRC, Università degli Studi di Milano, Milan, Italy. Electronic address:

Lecithin:cholesterol-acyl transferase (LCAT) plays a major role in cholesterol metabolism as it is the only extracellular enzyme able to esterify cholesterol. LCAT activity is required for lipoprotein remodeling and, most specifically, for the growth and maturation of HDLs. In fact, genetic alterations affecting LCAT functionality may cause a severe reduction in plasma levels of HDL-cholesterol with important clinical consequences. Read More

Metabolism 2021 03 9;116:154464. Epub 2020 Dec 9.

Center E. Grossi Paoletti, Dipartimento di Scienze Farmacologiche e Biomolecolari, Università degli Studi di Milano, Milano, Italy. Electronic address:

Objective: CER-001 is an HDL mimetic that has been tested in different pathological conditions, but never with LCAT deficiency. This study was designed to investigate whether the absence of LCAT affects the catabolic fate of CER-001, and to evaluate the effects of CER-001 on kidney disease associated with LCAT deficiency.

Methods: Lcat and wild-type mice received CER-001 (2. Read More

World J Hepatol 2020 Oct;12(10):722-737

Department of Medicine, Merkur University Hospital, Zagreb 10000, Croatia.

Combined liver and kidney transplantation (CLKT) is indicated in patients with failure of both organs, or for the treatment of end-stage chronic kidney disease (ESKD) caused by a genetic defect in the liver. The aim of the present review is to provide the most up-to-date overview of the rare conditions as indications for CLKT. They are major indications for CLKT in children. Read More

Arterioscler Thromb Vasc Biol 2021 01 22;41(1):360-376. Epub 2020 Oct 22.

Discovery Science and Technology Department (H.S., Y.F., N.W., K.K.), Daiichi Sankyo RD Novare, Co, Ltd, Tokyo, Japan.

Objective: Enhancement of LCAT (lecithin:cholesterol acyltransferase) activity has possibility to be beneficial for atherosclerosis. To evaluate this concept, we characterized our novel, orally administered, small-molecule LCAT activator DS-8190a, which was created from high-throughput screening and subsequent derivatization. We also focused on its mechanism of LCAT activation and the therapeutic activity with improvement of HDL (high-density lipoprotein) functionality. Read More

J Lipid Res 2020 12 30;61(12):1784-1788. Epub 2020 Sep 30.

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

Familial LCAT deficiency (FLD) is a rare genetic disorder of HDL metabolism, caused by loss-of-function mutations in the gene and characterized by a variety of symptoms including corneal opacities and kidney failure. Renal disease represents the leading cause of morbidity and mortality in FLD cases. However, the prognosis is not known and the rate of deterioration of kidney function is variable and unpredictable from patient to patient. Read More

Arterioscler Thromb Vasc Biol 2020 12 1;40(12):2829-2836. Epub 2020 Oct 1.

Institute of Cardiovascular Sciences and Key Laboratory of Molecular Cardiovascular Sciences, Ministry of Education (M.G., P.M., W.H., Y.W., G.L., X.X.), Peking University, Beijing, China.

Objective: LCAT (lecithin cholesterol acyltransferase) deficiency results in severe low HDL (high-density lipoprotein). Although whether LCAT is pro- or antiatherosclerosis was in debate in mouse studies, our previous study clearly shows that LCAT deficiency (LCAT) in hamster accelerates atherosclerotic development on high-fat diet. However, unlike in hypercholesterolemia and hypertriglyceridemia, whether LCAT deficiency could lead to spontaneous atherosclerosis has not been studied yet in animal models. Read More

J Pharmacol Exp Ther 2020 12 26;375(3):463-468. Epub 2020 Sep 26.

Centro E. Grossi Paoletti, Dipartimento di Scienze Farmacologiche e Biomolecolari (C.P., A.O., M.T., A.S., S.S., L.C.) and Dipartimento di Scienze Farmacologiche e Biomolecolari (T.L., I.E.), Università degli Studi di Milano, Milan, Italy; Specialty Medicine Research Laboratories I, Daiichi Sankyo Co., Ltd., Tokyo, Japan (K.K., N.K.); and Medical Affairs Planning Department, Daiichi Sankyo Co., Ltd., Tokyo, Japan (K.Y.)

Lecithin:cholesterol acyltransferase (LCAT) is a unique plasma enzyme able to esterify cholesterol, and it plays an important role in HDL maturation and promotion of reverse cholesterol transport. Familial LCAT deficiency (FLD; OMIM number 245900) is a rare recessive disease that results from loss-of-function mutations in the gene and has no cure. In this study, we assessed the in vitro efficacy of a novel small-molecule LCAT activator. Read More

Curr Opin Lipidol 2020 08;31(4):232-237

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

Purpose Of Review: Genetic LCAT deficiency is a rare metabolic disorder characterized by low-plasma HDL cholesterol levels. Clinical manifestations of the disease include corneal opacification, anemia, and renal disease, which represents the major cause of morbidity and mortality in carriers.

Recent Findings: Biochemical and clinical manifestations of the disease are very heterogeneous among carriers. Read More

J Lipid Res 2020 09 19;61(9):1287-1299. Epub 2020 Jun 19.

Division of Endocrinology and Metabolism, Department of Internal Medicine, Jichi Medical University, Shimotsuke 329-0498, Japan

The acyltransferase LCAT mediates FA esterification of plasma cholesterol. In vitro studies have shown that LCAT also FA-esterifies several oxysterols, but in vivo evidence is lacking. Here, we measured both free and FA-esterified forms of sterols in 206 healthy volunteers and 8 individuals with genetic LCAT deficiency, including familial LCAT deficiency (FLD) and fish-eye disease (FED). Read More

J Lipid Res 2020 08 1;61(8):1142-1149. Epub 2020 Jun 1.

Department of Nutrition, University of Oslo, Oslo, Norway

LCAT converts free cholesterol to cholesteryl esters in the process of reverse cholesterol transport. Familial LCAT deficiency (FLD) is a genetic disease that was first described by Kaare R. Norum and Egil Gjone in 1967. Read More

Curr Opin Lipidol 2020 04;31(2):71-79

Lipoprotein Metabolism Laboratory, Translational Vascular Medicine Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda.

Purpose Of Review: To review recent lecithin:cholesterol acyltransferas (LCAT)-based therapeutic approaches for atherosclerosis, acute coronary syndrome, and LCAT deficiency disorders.

Recent Findings: A wide variety of approaches to using LCAT as a novel therapeutic target have been proposed. Enzyme replacement therapy with recombinant human LCAT is the most clinically advanced therapy for atherosclerosis and familial LCAT deficiency (FLD), with Phase I and Phase 2A clinical trials recently completed. Read More

FASEB J 2020 03 23;34(3):3805-3819. Epub 2020 Jan 23.

Department of Biochemistry and Molecular Biology, Hubei Provincial Key Laboratory of Developmentally Originated Disease, Wuhan University School of Basic Medical Sciences, Wuhan, China.

High-density lipoprotein (HDL), a well-known atheroprotective factor, can be converted to proatherogenic particles in chronic inflammation. HDL-targeted therapeutic strategy for atherosclerotic cardiovascular disease (CVD) is currently under development. This study aims to assess the role of methionine sulfoxide reductase A (MsrA) in abnormal HDL and its related disorders in scavenger receptor class B type I deficient (SR-BI ) mice. Read More

Pharmacol Res Perspect 2020 02 29;8(1):e00554. Epub 2019 Dec 29.

Lipoprotein Metabolism Section Translational Vascular Medicine Branch National Heart Lung and Blood Institute National Institutes of Health Bethesda MD USA.

Familial lecithin:cholesterol acyltransferase (LCAT) deficiency (FLD) is a rare genetic disease characterized by low HDL-C levels, low plasma cholesterol esterification, and the formation of Lipoprotein-X (Lp-X), an abnormal cholesterol-rich lipoprotein particle. LCAT deficiency causes corneal opacities, normochromic normocytic anemia, and progressive renal disease due to Lp-X deposition in the glomeruli. Recombinant LCAT is being investigated as a potential therapy for this disorder. Read More