398 results match your criteria Biochimica et biophysica acta. Molecular and cell biology of lipids[Journal]


Lipid mediators in platelet concentrate and extracellular vesicles: Molecular mechanisms from membrane glycerophospholipids to bioactive molecules.

Biochim Biophys Acta Mol Cell Biol Lipids 2019 Apr 10. Epub 2019 Apr 10.

Finnish Red Cross Blood Service, Kivihaantie 7, 00310 Helsinki, Finland. Electronic address:

Platelets are collected for transfusion to patients with different hematological disorders, and for logistical reasons, platelets are stored as concentrates. Despite the carefully controlled conditions, platelets become activated during storage, and platelet concentrates (PLCs) may cause adverse inflammatory reactions in the recipients. We studied by mass spectrometry the lipidomic changes during storage of the clinical PLCs, the platelets isolated from PLCs, and the extracellular vesicles (EVs) thereof. Read More

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http://dx.doi.org/10.1016/j.bbalip.2019.03.011DOI Listing

Myristic acid specifically stabilizes diacylglycerol kinase δ protein in C2C12 skeletal muscle cells.

Biochim Biophys Acta Mol Cell Biol Lipids 2019 Apr 10. Epub 2019 Apr 10.

Department of Chemistry, Graduate School of Science, Chiba University, Chiba 263-8522, Japan. Electronic address:

Decreased levels of the δ isozyme of diacylglycerol kinase (DGK) in skeletal muscle attenuate glucose uptake and, consequently, are critical for the pathogenesis of type 2 diabetes. We recently found that free myristic acid (14:0), but not free palmitic acid (16:0), increased the DGKδ protein levels and enhanced glucose uptake in C2C12 myotube cells. However, it has been unclear how myristic acid regulates the level of DGKδ2 protein. Read More

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http://dx.doi.org/10.1016/j.bbalip.2019.04.003DOI Listing

Substrate channeling in the glycerol-3-phosphate pathway regulates the synthesis, storage and secretion of glycerolipids.

Biochim Biophys Acta Mol Cell Biol Lipids 2019 Apr 5. Epub 2019 Apr 5.

Atlantic Research Center, Depts. of Pediatrics and Biochemistry & Molecular Biology, Dalhousie University, Halifax, NS, Canada. Electronic address:

The successive acylation of glycerol-3-phosphate (G3P) by glycerol-3-phosphate acyltransferases and acylglycerol-3-phosphate acyltransferases produces phosphatidic acid (PA), a precursor for CDP-diacylglycerol-dependent phospholipid synthesis. PA is further dephosphorylated by LIPINs to produce diacylglycerol (DG), a substrate for the synthesis of triglyceride (TG) by DG acyltransferases and a precursor for phospholipid synthesis via the CDP-choline and CDP-ethanolamine (Kennedy) pathways. The channeling of fatty acids into TG for storage in lipid droplets and secretion in lipoproteins or phospholipids for membrane biogenesis is dependent on isoform expression, activity and localization of G3P pathway enzymes, as well as dietary and hormonal and tissue-specific factors. Read More

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http://dx.doi.org/10.1016/j.bbalip.2019.03.010DOI Listing

Saturated fatty acids induce NLRP3 activation in human macrophages through K efflux resulting from phospholipid saturation and Na, K-ATPase disruption.

Biochim Biophys Acta Mol Cell Biol Lipids 2019 Apr 3. Epub 2019 Apr 3.

Laboratory of Immunometabolism and Nutrition, GIGA-Inflammation, Infection & Immunity, University of Liège, Liège, Belgium. Electronic address:

NLRP3 inflammasome plays a key role in Western diet-induced systemic inflammation and was recently shown to mediate long-lasting trained immunity in myeloid cells. Saturated fatty acids (SFAs) are sterile triggers able to induce the assembly of the NLRP3 inflammasome in macrophages, leading to IL-1β secretion while unsaturated ones (UFAs) prevent SFAs-mediated NLRP3 activation. Unlike previous studies using LPS-primed bone marrow derived macrophages, we do not see any ROS or IRE-1α involvement in SFAs-mediated NLRP3 activation in human monocytes-derived macrophages. Read More

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http://dx.doi.org/10.1016/j.bbalip.2019.04.001DOI Listing

The role of cardiolipin concentration and acyl chain composition on mitochondrial inner membrane molecular organization and function.

Biochim Biophys Acta Mol Cell Biol Lipids 2019 Apr 2. Epub 2019 Apr 2.

Department of Nutrition, Gillings School of Global Public Health and School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA. Electronic address:

Cardiolipin (CL) is a key phospholipid of the mitochondria. A loss of CL content and remodeling of CL's acyl chains is observed in several pathologies. Strong shifts in CL concentration and acyl chain composition would presumably disrupt mitochondrial inner membrane biophysical organization. Read More

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http://dx.doi.org/10.1016/j.bbalip.2019.03.012DOI Listing
April 2019
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Lipid determinants of endocytosis and exocytosis in budding yeast.

Biochim Biophys Acta Mol Cell Biol Lipids 2019 Mar 24;1864(7):1005-1016. Epub 2019 Mar 24.

Technische Universität Darmstadt, Fachbereich Biologie, Schnittspahnstraße 10, 64287 Darmstadt, Germany. Electronic address:

Cells maintain physicochemical characteristics of membranes in order to allow for proper function of membrane-associated cellular processes, such as endocytosis and exocytosis. To investigate the interplay between membrane properties and biological processes, we applied lipid engineering approaches that allowed for systematic manipulation of fatty acid unsaturation and sterol biosynthesis, the main regulators of membrane fluidity. In combination with electrophysiological membrane capacitance measurements, we were able to study the dependence of the endo- and exocytic activity of Saccharomyces cerevisiae on membrane lipid composition in vivo. Read More

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http://dx.doi.org/10.1016/j.bbalip.2019.03.007DOI Listing
March 2019
1 Read
5.162 Impact Factor

Phosphatidate-mediated regulation of lipid synthesis at the nuclear/endoplasmic reticulum membrane.

Biochim Biophys Acta Mol Cell Biol Lipids 2019 Mar 22. Epub 2019 Mar 22.

Department of Food Science and the Rutgers Center for Lipid Research, New Jersey Institute for Food, Nutrition, and Health, Rutgers University, New Brunswick, NJ 08901, USA. Electronic address:

In yeast and higher eukaryotes, phospholipids and triacylglycerol are derived from phosphatidate at the nuclear/endoplasmic reticulum membrane. In de novo biosynthetic pathways, phosphatidate is channeled into membrane phospholipids via its conversion to CDP-diacylglycerol. Its dephosphorylation to diacylglycerol is required for the synthesis of triacylglycerol as well as for the synthesis of phosphatidylcholine and phosphatidylethanolamine via the Kennedy pathway. Read More

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https://linkinghub.elsevier.com/retrieve/pii/S13881981193004
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http://dx.doi.org/10.1016/j.bbalip.2019.03.006DOI Listing
March 2019
3 Reads

Effect of liver fatty acid binding protein (L-FABP) gene ablation on lipid metabolism in high glucose diet (HGD) pair-fed mice.

Biochim Biophys Acta Mol Cell Biol Lipids 2019 Mar 22;1864(7):985-1004. Epub 2019 Mar 22.

Department of Pathobiology, Texas A&M University, TVMC, College Station, TX 77843, United States of America. Electronic address:

Liver fatty acid binding protein (L-FABP) is the major fatty acid binding/"chaperone" protein in hepatic cytosol. Although fatty acids can be derived from the breakdown of dietary fat and glucose, relatively little is known regarding the impact of L-FABP on phenotype in the context of high dietary glucose. Potential impact was examined in wild-type (WT) and Lfabp gene ablated (LKO) female mice fed either a control or pair-fed high glucose diet (HGD). Read More

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http://dx.doi.org/10.1016/j.bbalip.2019.03.009DOI Listing

Hypercholesterolemia in young adult APOE mice alters epidermal lipid composition and impairs barrier function.

Biochim Biophys Acta Mol Cell Biol Lipids 2019 Mar 21;1864(7):976-984. Epub 2019 Mar 21.

Division of BioTherapeutics, Leiden Academic Centre for Drug Research, Leiden University, Leiden, Zuid-Holland, the Netherlands. Electronic address:

Long-term exposure to hypercholesterolemia induces the development of skin xanthoma's characterized by the accumulation of lipid-laden foam cells in humans and in mice. Early skin changes in response to hypercholesterolemia are however unknown. In this study, we investigated the skin lipid composition and associated barrier function in young adult low-density lipoprotein receptor knockout (LDLR) and apolipoprotein E knockout (APOE) mice, two commonly used hypercholesterolemic mouse models characterized by the accumulation of apolipoprotein B containing lipoproteins. Read More

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http://dx.doi.org/10.1016/j.bbalip.2019.03.008DOI Listing
March 2019
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Small-molecule inhibitors as potential therapeutics and as tools to understand the role of phospholipases A.

Biochim Biophys Acta Mol Cell Biol Lipids 2019 Jun 23;1864(6):941-956. Epub 2018 Aug 23.

Department of Chemistry, National and Kapodistrian University of Athens, Panepistimiopolis, Athens 15771, Greece. Electronic address:

Phospholipase A (PLA) enzymes are involved in various inflammatory pathological conditions including arthritis, cardiovascular and autoimmune diseases. The regulation of their catalytic activity is of high importance and a great effort has been devoted in developing synthetic inhibitors. We summarize the most important small-molecule synthetic PLA inhibitors developed to target each one of the four major types of human PLA (cytosolic cPLA, calcium-independent iPLA secreted sPLA and lipoprotein-associated LpPLA). Read More

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https://linkinghub.elsevier.com/retrieve/pii/S13881981183022
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http://dx.doi.org/10.1016/j.bbalip.2018.08.009DOI Listing
June 2019
5 Reads
5.162 Impact Factor

Lipid-metabolizing serine hydrolases in the mammalian central nervous system: endocannabinoids and beyond.

Biochim Biophys Acta Mol Cell Biol Lipids 2019 Jun 16;1864(6):907-921. Epub 2018 Aug 16.

Department of Chemistry, University of Virginia, Charlottesville, VA 22904, United States; Department of Pharmacology, University of Virginia, Charlottesville, VA 22908, United States; University of Virginia Cancer Center, University of Virginia, Charlottesville, VA 22903, United States. Electronic address:

The metabolic serine hydrolases hydrolyze ester, amide, or thioester bonds found in broad small molecule substrates using a conserved activated serine nucleophile. The mammalian central nervous system (CNS) express a diverse repertoire of serine hydrolases that act as (phospho)lipases or lipid amidases to regulate lipid metabolism and signaling vital for normal neurocognitive function and CNS integrity. Advances in genomic DNA sequencing have provided evidence for the role of these lipid-metabolizing serine hydrolases in neurologic, psychiatric, and neurodegenerative disorders. Read More

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https://linkinghub.elsevier.com/retrieve/pii/S13881981183021
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http://dx.doi.org/10.1016/j.bbalip.2018.08.007DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6433413PMC
June 2019
2 Reads

Cytosolic phospholipase A and lysophospholipid acyltransferases.

Biochim Biophys Acta Mol Cell Biol Lipids 2019 Jun 9;1864(6):838-845. Epub 2018 Aug 9.

Department of Lipidomics, Graduate School of Medicine, The University of Tokyo, Bunkyo-ku, Tokyo 113-0033, Japan; Department of Lipid Signaling, National Center for Global Health and Medicine, Shinjuku-ku, Tokyo 162-8655, Japan.

Phospholipase A (PLA) enzymes catalyze the hydrolysis of ester bonds at sn-2 positions of glycerophospholipids (PL), producing free fatty acids and lysophospholipids. In mammals, the PLA superfamily comprises more than 30 known enzymes, including various structurally and biochemically different enzymes with diverse biological functions. Some of the enzymes are involved in the production of lipid mediators, including eicosanoids and lysophospholipid-related lipid mediators. Read More

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http://dx.doi.org/10.1016/j.bbalip.2018.08.006DOI Listing
June 2019
1 Read

Group IID, IIE, IIF and III secreted phospholipase As.

Biochim Biophys Acta Mol Cell Biol Lipids 2019 Jun 31;1864(6):803-818. Epub 2018 Aug 31.

PRIME, Japan Agency for Medical Research and Development, 1-7-1 Otemachi, Chiyoda-ku, Tokyo 100-0004, Japan; Division of Bioscience and Bioindustry, Graduate School of Technology, Industrial and Social Sciences, Tokushima University, Tokushima 770-8513, Japan. Electronic address:

Among the 11 members of the secreted phospholipase A (sPLA) family, group IID, IIE, IIF and III sPLAs (sPLA-IID, -IIE, -IIF and -III, respectively) are "new" isoforms in the history of sPLA research. Relative to the better characterized sPLAs (sPLA-IB, -IIA, -V and -X), the enzymatic properties, distributions, and functions of these "new" sPLAs have remained obscure until recently. Our current studies using knockout and transgenic mice for a nearly full set of sPLAs, in combination with comprehensive lipidomics, have revealed unique and distinct roles of these "new" sPLAs in specific biological events. Read More

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http://dx.doi.org/10.1016/j.bbalip.2018.08.014DOI Listing

Roles of secreted phospholipase A group IIA in inflammation and host defense.

Biochim Biophys Acta Mol Cell Biol Lipids 2019 Jun 13;1864(6):789-802. Epub 2018 Sep 13.

Centre de Recherche du CHU de Québec, Université Laval, Department of Infectious Diseases and Immunity, Québec City, QC, Canada; Canadian National Transplantation Research Program, Edmonton, AB, Canada. Electronic address:

Among all members of the secreted phospholipase A (sPLA) family, group IIA sPLA (sPLA-IIA) is possibly the most studied enzyme. Since its discovery, many names have been associated with sPLA-IIA, such as "non-pancreatic", "synovial", "platelet-type", "inflammatory", and "bactericidal" sPLA Whereas the different designations indicate comprehensive functions or sources proposed for this enzyme, the identification of the precise roles of sPLA-IIA has remained a challenge. This can be attributed to: the expression of the enzyme by various cells of different lineages, its limited activity towards the membranes of immune cells despite its expression following common inflammatory stimuli, its ability to interact with certain proteins independently of its catalytic activity, and its absence from multiple commonly used mouse models. Read More

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http://dx.doi.org/10.1016/j.bbalip.2018.08.017DOI Listing

Phospholipase A catalysis and lipid mediator lipidomics.

Biochim Biophys Acta Mol Cell Biol Lipids 2019 Jun 23;1864(6):766-771. Epub 2018 Aug 23.

Department of Chemistry and Biochemistry, Department of Pharmacology, School of Medicine, University of California, San Diego, La Jolla, CA 92093-0601, United States of America. Electronic address:

Phospholipase A (PLA) enzymes are the upstream regulators of the eicosanoid pathway liberating free arachidonic acid from the sn-2 position of membrane phospholipids. Free intracellular arachidonic acid serves as a substrate for the eicosanoid biosynthetic enzymes including cyclooxygenases, lipoxygenases, and cytochrome P450s that lead to inflammation. The Group IVA cytosolic (cPLA), Group VIA calcium-independent (iPLA), and Group V secreted (sPLA) are three well-characterized human enzymes that have been implicated in eicosanoid formation. Read More

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https://linkinghub.elsevier.com/retrieve/pii/S13881981183023
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http://dx.doi.org/10.1016/j.bbalip.2018.08.010DOI Listing
June 2019
2 Reads

ER platforms mediating autophagosome generation.

Biochim Biophys Acta Mol Cell Biol Lipids 2019 Mar 16. Epub 2019 Mar 16.

Signalling Programme, Babraham Institute, Babraham, Cambridge, CB223AT, UK.

The origin of the autophagosomal membrane started to be debated by scientists working in the field within one year of the modern definition of autophagy in 1963. There is now converging evidence from older and newer studies that the endoplasmic reticulum is involved in formation of autophagosomes. Thus, it is possible to trace from early morphological work - done without the benefit of molecular descriptions - to recent studies - dissecting how specific proteins nucleate autophagosome biogenesis - a long series of experimental findings that are beginning to answer the 55-year old question with some confidence. Read More

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http://dx.doi.org/10.1016/j.bbalip.2019.03.005DOI Listing

Involvement of pericardial adipose tissue in cardiac fibrosis of dietary-induced obese minipigs- Role of mitochondrial function.

Biochim Biophys Acta Mol Cell Biol Lipids 2019 Mar 11;1864(7):957-965. Epub 2019 Mar 11.

Department of Animal Science and Technology, National Taiwan University, No. 50, Lane 155, Sec 3, Keelung Rd, Taipei 10672, Taiwan. Electronic address:

Background: Heart is a high energy demand organ and cardiac fat is the main local energy source for heart. Alteration in cardiac fat may affect cardiac energy and contribute to heart dysfunction. We previously observed a link between alteration in pericardial fat (PAT) and local adverse effects on myocardial fibrosis in obese minipigs. Read More

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http://dx.doi.org/10.1016/j.bbalip.2019.03.004DOI Listing

Sustained phospholipase C stimulation of H9c2 cardiomyoblasts by vasopressin induces an increase in CDP-diacylglycerol synthase 1 (CDS1) through protein kinase C and cFos.

Biochim Biophys Acta Mol Cell Biol Lipids 2019 Mar 9. Epub 2019 Mar 9.

Dept. of Neuroscience, Physiology and Pharmacology, Division of Biosciences, University College London, London WC1E 6JJ, UK. Electronic address:

Chronic stimulation (24 h) with vasopressin leads to hypertrophy in H9c2 cardiomyoblasts and this is accompanied by continuous activation of phospholipase C. Consequently, vasopressin stimulation leads to a depletion of phosphatidylinositol levels. The substrate for phospholipase C is phosphatidylinositol (4, 5) bisphosphate (PIP) and resynthesis of phosphatidylinositol and its subsequent phosphorylation maintains the supply of PIP. Read More

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http://dx.doi.org/10.1016/j.bbalip.2019.03.002DOI Listing
March 2019
5.162 Impact Factor

A carotenoid oxygenase is responsible for muscle coloration in scallop.

Biochim Biophys Acta Mol Cell Biol Lipids 2019 Mar 9;1864(7):966-975. Epub 2019 Mar 9.

MOE Key Laboratory of Marine Genetics and Breeding, College of Marine Life Sciences, Ocean University of China, Qingdao 266003, China; Laboratory for Marine Fisheries Science and Food Production Processes, Qingdao National Laboratory for Marine Science and Technology, Qingdao 266237, China. Electronic address:

As lipid microconstituents mainly of plant origin, carotenoids are essential nutrients for humans and animals, and carotenoid coloration represents an important meat quality parameter for many farmed animals. Currently, the mechanism of carotenoid bioavailability in animals is largely unknown mainly due to the limited approaches applied, the shortage of suitable model systems and the restricted taxonomic focus. The mollusk Yesso scallop (Patinopecten yessoensis) possessing orange adductor muscle with carotenoid deposition, provides a unique opportunity to research the mechanism underlying carotenoid utilization in animals. Read More

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http://dx.doi.org/10.1016/j.bbalip.2019.03.003DOI Listing
March 2019
1 Read
5.162 Impact Factor

An accurate and versatile method for determining the acyl group-introducing position of lysophospholipid acyltransferases.

Biochim Biophys Acta Mol Cell Biol Lipids 2019 Mar 7. Epub 2019 Mar 7.

Laboratory of Molecular and Cellular Biochemistry, Graduate School of Pharmaceutical Sciences, Tohoku University, 6-3 Aoba, Aramaki, Aoba-Ku, Sendai 980-8578, Japan; AMED-LEAP, Chiyoda-ku, Tokyo 100-0004, Japan. Electronic address:

Lysophospholipid acyltransferases (LPLATs) incorporate a fatty acid into the hydroxyl group of lysophospholipids (LPLs) and are critical for determining the fatty acid composition of phospholipids. Previous studies have focused mainly on their molecular identification and their substrate specificity regarding the polar head groups and acyl-CoAs. However, little is known about the positional specificity of the hydroxyl group of the glycerol backbone (sn-2 or sn-1) at which LPLATs introduce a fatty acid. Read More

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http://dx.doi.org/10.1016/j.bbalip.2019.02.008DOI Listing

Effects of triacylglycerol on the structural remodeling of human plasma very low- and low-density lipoproteins.

Biochim Biophys Acta Mol Cell Biol Lipids 2019 Mar 5. Epub 2019 Mar 5.

Department of Physiology & Biophysics, Boston University School of Medicine, Boston, MA 02118, USA; Amyloidosis Treatment and Research Center, Boston University School of Medicine, Boston, MA, USA.

Very low-density lipoprotein (VLDL) is the main plasma carrier of triacylglycerol that is elevated in pathological conditions such as diabetes, metabolic syndrome, obesity and dyslipidemia. How variations in triacylglycerol levels influence structural stability and remodeling of VLDL and its metabolic product, low-density lipoproteins (LDL), is unknown. We applied a biochemical and biophysical approach using lipoprotein remodeling by lipoprotein lipase and cholesterol ester transfer protein, along with thermal denaturation that mimics key aspects of lipoprotein remodeling in vivo. Read More

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http://dx.doi.org/10.1016/j.bbalip.2019.03.001DOI Listing
March 2019
1 Read

Effects on hepatic lipid metabolism in human hepatoma cells following overexpression of TGFβ induced factor homeobox 1 or 2.

Biochim Biophys Acta Mol Cell Biol Lipids 2019 May 27;1864(5):756-762. Epub 2019 Feb 27.

Division of Clinical Chemistry, Department of Laboratory Medicine, Karolinska Institutet at Karolinska University Hospital Huddinge, Stockholm, Sweden. Electronic address:

Transforming growth factor β induced factor homeobox (TGIF) 1 and 2 are two transcriptional repressors. Although TGIF1 has been found to be involved in lipid metabolism, no studies have yet investigated the role of TGIF2 in hepatic lipid metabolism. Here we aim to investigate effects on hepatic lipid metabolism following overexpression of the human and mouse TGIF1 and TGIF2 protein. Read More

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http://dx.doi.org/10.1016/j.bbalip.2019.02.009DOI Listing
May 2019
1 Read

MicroRNA-425 controls lipogenesis and lipolysis in adipocytes.

Biochim Biophys Acta Mol Cell Biol Lipids 2019 May 26;1864(5):744-755. Epub 2019 Feb 26.

Key Laboratory of Pig Industry Sciences, Ministry of Agriculture, Rongchang 402460, China. Electronic address:

An increasing number of studies have demonstrated that some microRNAs participate in the regulation of growth and development of adipocytes. The present study shows that microRNA-425-5p (miR-425) is a novel strong regulator of adipogenesis and adipolysis in adipocytes. Forced expression of miR-425 in mice promoted body fat accumulation and the development of obesity due to high-fat intake, whereas silencing miR-425 prevented mice from being obese. Read More

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http://dx.doi.org/10.1016/j.bbalip.2019.02.007DOI Listing
May 2019
6 Reads

CRISPR/Cas9-mediated knockout of Abcd1 and Abcd2 genes in BV-2 cells: novel microglial models for X-linked Adrenoleukodystrophy.

Biochim Biophys Acta Mol Cell Biol Lipids 2019 May 13;1864(5):704-714. Epub 2019 Feb 13.

Laboratoire Bio-PeroxIL EA7270, University of Bourgogne Franche-Comté, Dijon, France. Electronic address:

X-linked adrenoleukodystrophy (X-ALD), the most frequent peroxisomal disorder, is associated with mutation in the ABCD1 gene which encodes a peroxisomal ATP-binding cassette transporter for very long-chain fatty acids (VLCFA). The biochemical hallmark of the disease is the accumulation of VLCFA. Peroxisomal defect in microglia being now considered a priming event in the pathology, we have therefore generated murine microglial cells mutated in the Abcd1 gene and its closest homolog, the Abcd2 gene. Read More

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http://dx.doi.org/10.1016/j.bbalip.2019.02.006DOI Listing
May 2019
3 Reads

Novel functions of phospholipase As: Overview.

Authors:
Makoto Murakami

Biochim Biophys Acta Mol Cell Biol Lipids 2019 Jun 13;1864(6):763-765. Epub 2019 Feb 13.

Laboratory of Microenvironmental and Metabolic Health Science, Center for Disease Biology and Integrative Medicine, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, Japan; AMED-CREST, Japan Agency for Medical Research and Development, 1-7-1 Otemachi, Chiyoda-ku, Tokyo 100-0004, Japan. Electronic address:

The phospholipase A (PLA) family comprises a group of lipolytic enzymes that typically hydrolyze the sn-2 position of (glycerol) phospholipids to give rise to fatty acids and lysophospholipids. The mammalian genome encodes more than 30 (even 50) PLAs or related enzymes, which are classified into several subfamilies on the basis of their structures and functions. The PLA family has been implicated not only in signal transduction by producing lipid mediators, but also in membrane homeostasis, energy production, and barrier function. Read More

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http://dx.doi.org/10.1016/j.bbalip.2019.02.005DOI Listing

Gene-gene and gene-environment interactions in lipodystrophy: Lessons learned from natural PPARγ mutants.

Biochim Biophys Acta Mol Cell Biol Lipids 2019 May 8;1864(5):715-732. Epub 2019 Feb 8.

Center for Molecular Medicine, University Medical Center Utrecht, Utrecht University, Utrecht, the Netherlands. Electronic address:

Monogenic lipodystrophies are a heterogeneous group of rare disorders characterized by a lack of adipose tissue (AT), all of which predispose patients to the development of insulin resistance and its related metabolic sequelae. The extent of AT loss ranges from partial, as in familial partial lipodystrophy (FPLD), to a total absence of metabolically active AT in congenital generalized lipodystrophy (CGL) and is generally associated with the severity of metabolic complications. Significant genetic, allelic, phenotypic, and clinical heterogeneity exists among the lipodystrophies. Read More

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http://dx.doi.org/10.1016/j.bbalip.2019.02.002DOI Listing
May 2019
1 Read

Hepatic stellate cell activation: A source for bioactive lipids.

Biochim Biophys Acta Mol Cell Biol Lipids 2019 May 5;1864(5):629-642. Epub 2019 Feb 5.

Department of Medicine, Vagelos College of Physicians and Surgeons, Columbia University, 630 West 168(th) Street, New York, NY 10032, USA.

Hepatic stellate cells (HSCs) are non-parenchymal liver cells that characteristically contain multiple retinoid (vitamin A)-containing lipid droplets. In this study, we addressed the metabolic fate of non-retinoid lipids originating from lipid droplet loss during HSCs activation. UPLC/MS/MS and qRT-PCR were used to monitor the lipid composition and mRNA expression of selected genes regulating lipid metabolism in freshly isolated, overnight-, 3- and 7-day cultures or primary mouse HSCs. Read More

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http://dx.doi.org/10.1016/j.bbalip.2019.02.004DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6414233PMC
May 2019
7 Reads

Group VIA phospholipase A2 deficiency in mice chronically fed with high-fat-diet attenuates hepatic steatosis by correcting a defect of phospholipid remodeling.

Biochim Biophys Acta Mol Cell Biol Lipids 2019 May 5;1864(5):662-676. Epub 2019 Feb 5.

Department of Internal Medicine IV, Heidelberg University Hospital, Im Neuenheimer Feld 410, 69120 Heidelberg, Germany. Electronic address:

A defect of hepatic remodeling of phospholipids (PL) is seen in non-alcoholic fatty liver disease and steatohepatitis (NASH) indicating pivotal role of PL metabolism in this disease. The deletion of group VIA calcium-independent phospholipase A2 (iPla2β) protects ob/ob mice from hepatic steatosis (BBAlip 1861, 2016, 440-461), however its role in high-fat diet (HFD)-induced NASH is still elusive. Here, wild-type and iPla2β-null mice were subjected to chronic feeding with HFD for 6 months. Read More

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http://dx.doi.org/10.1016/j.bbalip.2019.01.012DOI Listing
May 2019
4 Reads

iPla2β deficiency in mice fed with MCD diet does not correct the defect of phospholipid remodeling but attenuates hepatocellular injury via an inhibition of lipid uptake genes.

Biochim Biophys Acta Mol Cell Biol Lipids 2019 May 5;1864(5):677-687. Epub 2019 Feb 5.

Department of Internal Medicine IV, University of Heidelberg Hospital, Im Neuenheimer Feld 410, 69120 Heidelberg, Germany. Electronic address:

Group VIA calcium-independent phospholipase A2 (iPla2β) is among modifier genes of non-alcoholic fatty liver disease which leads to non-alcoholic steatohepatitis (NASH). Consistently, iPla2β deletion protects hepatic steatosis and obesity in genetic ob/ob and obese mice chronically fed with high-fat diet by replenishing the loss of hepatic phospholipids (PL). As mouse feeding with methionine- and choline-deficient (MCD) diet is a model of lean NASH, we tested whether iPla2β-null mice could still be protected since PL syntheses are disturbed. Read More

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http://dx.doi.org/10.1016/j.bbalip.2019.02.003DOI Listing
May 2019
2 Reads

Cardiolipin-deficient cells depend on anaplerotic pathways to ameliorate defective TCA cycle function.

Biochim Biophys Acta Mol Cell Biol Lipids 2019 May 5;1864(5):654-661. Epub 2019 Feb 5.

Department of Biological Sciences, Wayne State University, Detroit, MI 48202, United States of America. Electronic address:

Previous studies have shown that the cardiolipin (CL)-deficient yeast mutant, crd1Δ, has decreased levels of acetyl-CoA and decreased activities of the TCA cycle enzymes aconitase and succinate dehydrogenase. These biochemical phenotypes are expected to lead to defective TCA cycle function. In this study, we report that signaling and anaplerotic metabolic pathways that supplement defects in the TCA cycle are essential in crd1Δ mutant cells. Read More

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http://dx.doi.org/10.1016/j.bbalip.2019.02.001DOI Listing
May 2019
2 Reads

Insights into the histology of planarian flatworm Phagocata gracilis based on location specific, intact lipid information provided by GCIB-ToF-SIMS imaging.

Biochim Biophys Acta Mol Cell Biol Lipids 2019 May 4;1864(5):733-743. Epub 2019 Feb 4.

NESACBIO, University of Washington, Seattle, WA, United States of America; Department of Bioengineering, University of Washington, Seattle, WA, United States of America. Electronic address:

Planarian flatworms are known as the masters of regeneration, re-growing an entire organism from as little as 1/279th part of their body. While the proteomics of these processes has been studied extensively, the planarian lipodome remains relatively unknown. In this study we investigate the lipid profile of planarian tissue sections with imaging Time-of-Flight - Secondary-Ion-Mass-Spectrometry (ToF-SIMS). Read More

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http://dx.doi.org/10.1016/j.bbalip.2019.01.011DOI Listing
May 2019
2 Reads
5.162 Impact Factor

Plant phospholipase D mining unravels new conserved residues important for catalytic activity.

Biochim Biophys Acta Mol Cell Biol Lipids 2019 May 26;1864(5):688-703. Epub 2019 Jan 26.

Univ Lyon, Université Lyon 1, Institut de Chimie et de Biochimie Moléculaires et Supramoléculaires (ICBMS), UMR 5246 CNRS, Métabolisme, Enzymes et Mécanismes Moléculaires (MEM(2)), Bât Raulin, 43 Bd du 11 Novembre 1918, F-69622 Villeurbanne Cedex, France. Electronic address:

Phospholipase D (PLD) is a key enzyme involved in numerous processes in all living organisms. Hydrolysis of phospholipids by PLD allows the release of phosphatidic acid which is a crucial intermediate of multiple pathways and signaling reactions, including tumorigenesis in mammals and defense responses in plants. One common feature found in the plant alpha isoform (PLDα), in some PLD from microbes and in all PLD from eukaryotes, is a duplicated motif named HKD involved in the catalysis. Read More

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https://linkinghub.elsevier.com/retrieve/pii/S13881981183026
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http://dx.doi.org/10.1016/j.bbalip.2019.01.008DOI Listing
May 2019
10 Reads

miR-24 is involved in vertebrate LC-PUFA biosynthesis as demonstrated in marine teleost Siganus canaliculatus.

Biochim Biophys Acta Mol Cell Biol Lipids 2019 May 23;1864(5):619-628. Epub 2019 Jan 23.

College of Marine Sciences, South China Agricultural University, Guangzhou 510642, China. Electronic address:

Recently, microRNAs (miRNAs) have emerged as crucial regulators of lipid metabolism. However, the miRNA-mediated regulatory mechanism on long-chain (≥C) polyunsaturated fatty acids (LC-PUFA) biosynthesis in vertebrates remains largely unknown. Here, we address a potentially important role of miRNA-24 (miR-24) in the regulation of LC-PUFA biosynthesis in rabbitfish Siganus canaliculatus. Read More

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http://dx.doi.org/10.1016/j.bbalip.2019.01.010DOI Listing
May 2019
15 Reads

Prostaglandin D-glycerol ester decreases carrageenan-induced inflammation and hyperalgesia in mice.

Biochim Biophys Acta Mol Cell Biol Lipids 2019 May 24;1864(5):609-618. Epub 2019 Jan 24.

Bioanalysis and Pharmacology of Bioactive Lipids Research Group, Louvain Drug Research Institute, Université catholique de Louvain, Avenue Mounier 72 (B1.72.01), 1200 Brussels, Belgium. Electronic address:

Pain is one of the cardinal signs of inflammation and is present in many inflammatory conditions. Therefore, anti-inflammatory drugs such as NSAIDs also have analgesic properties. We previously showed that prostaglandin D-glycerol ester (PGD-G), endogenously produced by cyclooxygenase-2 from the endocannabinoid 2-arachidonoylglycerol, has anti-inflammatory effects in vitro and in vivo that are partly mediated by DP1 receptor activation. Read More

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http://dx.doi.org/10.1016/j.bbalip.2019.01.009DOI Listing
May 2019
3 Reads

The N-terminal homology (ENTH) domain of Epsin 1 is a sensitive reporter of physiological PI(4,5)P dynamics.

Biochim Biophys Acta Mol Cell Biol Lipids 2019 Mar 16;1864(3):433-442. Epub 2018 Aug 16.

Department of Neurophysiology, Institute of Physiology and Pathophysiology, Philipps-University Marburg, 35037 Marburg, Germany; DFG Research Training Group, Membrane Plasticity in Tissue Development and Remodeling, GRK 2213, Philipps-University, Germany; Center for Mind, Brain and Behavior (CMBB), Universities of Marburg and Giessen, Germany.

Phospholipase Cβ (PLCβ)-induced depletion of phosphatidylinositol-(4,5)-bisphosphate (PI(4,5)P) transduces a plethora of signals into cellular responses. Importance and diversity of PI(4,5)P-dependent processes led to strong need for biosensors of physiological PI(4,5)P dynamics applicable in live-cell experiments. Membrane PI(4,5)P can be monitored with fluorescently-labelled phosphoinositide (PI) binding domains that associate to the membrane depending on PI(4,5)P levels. Read More

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https://linkinghub.elsevier.com/retrieve/pii/S13881981183020
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http://dx.doi.org/10.1016/j.bbalip.2018.08.005DOI Listing
March 2019
4 Reads

Omega 3 rich diet modulates energy metabolism via GPR120-Nrf2 crosstalk in a novel antioxidant mouse model.

Biochim Biophys Acta Mol Cell Biol Lipids 2019 Apr 16;1864(4):466-488. Epub 2019 Jan 16.

Department of Biomedical Sciences, Joan C. Edwards School of Medicine, Marshall University, 1700 3rd Ave, Huntington, WV 25755-0001, United States. Electronic address:

With obesity rates reaching epidemic proportions, more studies concentrated on reducing the risk and treating this epidemic are vital. Redox stress is an important metabolic regulator involved in the pathophysiology of cardiovascular disease, Type 2 diabetes, and obesity. Oxygen and nitrogen-derived free radicals alter glucose and lipid homeostasis in key metabolic tissues, leading to increases in risk of developing metabolic syndrome. Read More

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http://dx.doi.org/10.1016/j.bbalip.2019.01.002DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6414231PMC
April 2019
16 Reads

Glycosylation of human plasma lipoproteins reveals a high level of diversity, which directly impacts their functional properties.

Biochim Biophys Acta Mol Cell Biol Lipids 2019 May 12;1864(5):643-653. Epub 2019 Jan 12.

Genos Glycoscience Research Laboratory, Borongajska cesta 83H, HR-10 000 Zagreb, Croatia.

Aims: Human plasma lipoproteins are known to contain various glycan structures whose composition and functional importance are starting to be recognized. We assessed N-glycosylation of human plasma HDL and LDL and the role of their glycomes in cellular cholesterol metabolism.

Methods: N-glycomic profiles of native and neuraminidase-treated HDL and LDL were obtained using HILIC-UHPLC-FLD. Read More

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http://dx.doi.org/10.1016/j.bbalip.2019.01.005DOI Listing
May 2019
14 Reads

Tafazzin-dependent cardiolipin composition in C6 glioma cells correlates with changes in mitochondrial and cellular functions, and cellular proliferation.

Biochim Biophys Acta Mol Cell Biol Lipids 2019 Apr 9;1864(4):452-465. Epub 2019 Jan 9.

Institute of Clinical Chemistry, Department of Pathobiochemistry, Medical Faculty, Otto-von-Guericke University Magdeburg, Leipziger Str. 44, D-39120 Magdeburg, Germany.

The mitochondrial phospholipid cardiolipin (CL) has been implicated with mitochondrial morphology, function and, more recently, with cellular proliferation. Tafazzin, an acyltransferase with key functions in CL remodeling determining actual CL composition, affects mitochondrial oxidative phosphorylation. Here, we show that the CRISPR-Cas9 mediated knock-out of tafazzin (Taz) is associated with substantial alterations of various mitochondrial and cellular characteristics in C6 glioma cells. Read More

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http://dx.doi.org/10.1016/j.bbalip.2019.01.006DOI Listing
April 2019
2 Reads

Hepatocyte-specific lysosomal acid lipase deficiency protects mice from diet-induced obesity but promotes hepatic inflammation.

Biochim Biophys Acta Mol Cell Biol Lipids 2019 Apr 9;1864(4):500-511. Epub 2019 Jan 9.

Gottfried Schatz Research Center, Medical University of Graz, Graz, Austria; BioTechMed-Graz, Graz, Austria. Electronic address:

Lysosomal acid lipase (LAL) hydrolyzes cholesteryl esters (CE) and triglycerides (TG) to generate fatty acids (FA) and cholesterol. LAL deficiency (LAL-D) in both humans and mice leads to hepatomegaly, hypercholesterolemia, and shortened life span. Despite its essential role in lysosomal neutral lipid catabolism, the cell type-specific contribution of LAL to disease progression is still elusive. Read More

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http://dx.doi.org/10.1016/j.bbalip.2019.01.007DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6372077PMC
April 2019
19 Reads

Olfactory receptor 43 reduces hepatic lipid accumulation and adiposity in mice.

Biochim Biophys Acta Mol Cell Biol Lipids 2019 Apr 9;1864(4):489-499. Epub 2019 Jan 9.

Department of Biotechnology, School of Life Sciences and Biotechnology for BK21 PLUS, Korea University, Seoul 02841, Republic of Korea. Electronic address:

Olfactory receptors are primarily expressed in nasal olfactory epithelium, but these receptors are also ectopically expressed in diverse tissues. In this study, we investigated the biological functions of Olfr43, a mouse homolog of human OR1A1, in cultured hepatocytes and mice to assess its functionality in lipid metabolism. Olfr43 was expressed in mouse hepatocytes, and Olfr43 activation by a known ligand, (-)-carvone, stimulated cAMP response element-binding protein (CREB) activity. Read More

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http://dx.doi.org/10.1016/j.bbalip.2019.01.004DOI Listing
April 2019
8 Reads

ATP-binding cassette transporter G1 deficiency is associated with mild glucocorticoid insufficiency in mice.

Biochim Biophys Acta Mol Cell Biol Lipids 2019 Apr 10;1864(4):443-451. Epub 2019 Jan 10.

Division of BioTherapeutics, Leiden Academic Centre for Drug Research, Gorlaeus Laboratories, Einsteinweg 55, 2333CC Leiden, the Netherlands.

Objective: Since cholesterol is the sole precursor for glucocorticoid synthesis, it is hypothesized that genetic defects in proteins that impact the cellular cholesterol pool may underlie glucocorticoid insufficiency in humans. In the current study, we specifically focused on the cholesterol efflux mediator ATP-binding cassette transporter G1 (ABCG1) as gene candidate.

Methods: The adrenal transcriptional response to fasting stress was measured in wild-type mice to identify putative novel gene candidates. Read More

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http://dx.doi.org/10.1016/j.bbalip.2019.01.003DOI Listing
April 2019
18 Reads

Apolipoprotein D overexpression alters hepatic prostaglandin and omega fatty acid metabolism during the development of a non-inflammatory hepatic steatosis.

Biochim Biophys Acta Mol Cell Biol Lipids 2019 Apr 7;1864(4):522-531. Epub 2019 Jan 7.

Molecular Metabolism of Lipids Laboratory, BioMed Research Center, Biological Sciences Department, University of Quebec in Montreal (UQAM), Canada. Electronic address:

Apolipoprotein D (ApoD) is a secreted lipocalin associated with neuroprotection and lipid metabolism. Overexpression of ApoD in mouse neural tissue induces the development of a non-inflammatory hepatic steatosis in 12-month-old transgenic animals. Previous data indicates that accumulation of arachidonic acid, ApoD's preferential ligand, and overactivation of PPARγ are likely the driving forces in the development of the pathology. Read More

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https://linkinghub.elsevier.com/retrieve/pii/S13881981183016
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http://dx.doi.org/10.1016/j.bbalip.2019.01.001DOI Listing
April 2019
8 Reads

1-Deoxysphingolipids.

Biochim Biophys Acta Mol Cell Biol Lipids 2019 Apr 6;1864(4):512-521. Epub 2019 Jan 6.

Institute for Clinical Chemistry, University Hospital Zurich, Switzerland; Zurich Center for Integrative Human Physiology (ZIHP), University of Zurich, Switzerland. Electronic address:

Sphingolipids (SLs) are fundamental components of eukaryotic cells. 1-Deoxysphingolipids differ structurally from canonical SLs as they lack the essential C1-OH group. Consequently, 1-deoxysphingolipids cannot be converted to complex sphingolipids and are not degraded over the canonical catabolic pathways. Read More

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http://dx.doi.org/10.1016/j.bbalip.2018.12.013DOI Listing
April 2019
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Functional characterization of novel ALOX15 orthologs representing key steps in mammalian evolution supports the Evolutionary Hypothesis of reaction specificity.

Biochim Biophys Acta Mol Cell Biol Lipids 2019 Mar 29;1864(3):372-385. Epub 2018 Dec 29.

Institute of Biochemistry, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, Berlin Institute of Health, Chariteplatz 1, D-10117 Berlin, Germany. Electronic address:

Arachidonic acid lipoxygenases (ALOXs) are lipid-metabolizing enzymes that have been implicated in cell differentiation, but also in the pathogenesis of inflammatory, hyperproliferative and neurological diseases. Most mammalian genomes involve six or seven functional ALOX genes and among the corresponding ALOX-isoforms the ALOX15 orthologs are somewhat unique since they exhibit variable reaction specificity using arachidonic acid as substrate. The Evolutionary Hypothesis of mammalian ALOX15 reaction specificity (Prog. Read More

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http://dx.doi.org/10.1016/j.bbalip.2018.12.016DOI Listing

Arginylation regulates adipogenesis by regulating expression of PPARγ at transcript and protein level.

Biochim Biophys Acta Mol Cell Biol Lipids 2019 Apr 28;1864(4):596-607. Epub 2018 Dec 28.

Department of Biotechnology, National Institute of Technology, Durgapur, West Bengal 713209, India. Electronic address:

Protein modification by arginylation regulates protein stability, function and interaction. The loss of arginylation disrupts a diverse set of fundamental cellular processes from proliferation to death. In the current study, role of arginylation in cell differentiation is investigated. Read More

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http://dx.doi.org/10.1016/j.bbalip.2018.12.015DOI Listing

n-3 polyunsaturated N-acylethanolamines are CB cannabinoid receptor-preferring endocannabinoids.

Biochim Biophys Acta Mol Cell Biol Lipids 2018 Nov 7;1863(11):1433-1440. Epub 2018 Aug 7.

School of Life Sciences, University of Nottingham Medical School, Nottingham NG7 2UH, England, United Kingdom of Great Britain and Northern Ireland. Electronic address:

Anandamide, the first identified endogenous cannabinoid and TRPV1 agonist, is one of a series of endogenous N-acylethanolamines, NAEs. We have generated novel assays to quantify the levels of multiple NAEs in biological tissues and their rates of hydrolysis through fatty acid amide hydrolase. This range of NAEs was also tested in rapid response assays of CB, CB cannabinoid and TRPV1 receptors. Read More

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http://dx.doi.org/10.1016/j.bbalip.2018.08.003DOI Listing
November 2018
7 Reads

Super-resolution microscopy localizes perilipin 5 at lipid droplet-mitochondria interaction sites and at lipid droplets juxtaposing to perilipin 2.

Biochim Biophys Acta Mol Cell Biol Lipids 2018 Nov 31;1863(11):1423-1432. Epub 2018 Aug 31.

Department of Nutrition and Movement Sciences, Maastricht University Medical Centre+, 6200 MD Maastricht, the Netherlands; NUTRIM School for Nutrition and Translational Research in Metabolism, Maastricht, the Netherlands. Electronic address:

Objective: Intramyocellular lipid droplets (LD) and their coat proteins PLIN2 and PLIN5 are involved in lipolysis, with a putative role for PLIN5 in mitochondrial tethering. Reportedly, these proteins co-localize and cover the surface of the LD. To provide the spatial basis for understanding how these proteins possess their distinct roles, we examined the precise location of PLIN2 and PLIN5 and explored PLIN5 presence at LD-mitochondria contact sites using Stimulated emission depletion (STED) microscopy and correlative light-electron microscopy (CLEM) in human skeletal muscle sections. Read More

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http://dx.doi.org/10.1016/j.bbalip.2018.08.016DOI Listing
November 2018
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Molecular mechanisms of regulation of sphingosine kinase 1.

Biochim Biophys Acta Mol Cell Biol Lipids 2018 Nov 30;1863(11):1413-1422. Epub 2018 Aug 30.

Department of Medicine, The Stony Brook Cancer Center, Stony Brook University, Stony Brook, NY 11790, USA; Northport Veterans Affairs Medical Center, Northport, NY 11768, USA. Electronic address:

Within the last 3 decades, there has been intense study of bioactive sphingolipids and the enzymes which metabolize those lipids. One enzyme is the critical lipid kinase sphingosine kinase 1 (SK1), which produces the potent and pleiotropic signaling lipid, sphingosine 1-phosphate (S1P). SK1 and S1P have been implicated in a host of different diseases including cancer, chronic inflammation, and metabolic diseases. Read More

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http://dx.doi.org/10.1016/j.bbalip.2018.08.015DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6436826PMC
November 2018

Polyunsaturated C fatty acids derivatized with Gly and Ile as an additional tool for studies of the catalytic evolution of fungal 8- and 9-dioxygenases.

Authors:
Ernst H Oliw

Biochim Biophys Acta Mol Cell Biol Lipids 2018 Nov 24;1863(11):1378-1387. Epub 2018 Aug 24.

Division of Biochemical Pharmacology, Department of Pharmaceutical Biosciences, Uppsala University, Box 591, SE-751 24 Uppsala, Sweden. Electronic address:

The fungal linoleate diol synthase (LDS) family contains over twenty characterized 8-, 9-, and 10-dioxygenases (DOX), usually fused to catalytically competent cytochromes P450. Crystal structures are not available, but indirect evidence suggests that linoleic acid enters the active site of 8R-DOX-LDS headfirst and enters 9S-DOX-allene oxide synthase (AOS) with the ω-end (tail) first. Fatty acids derivatized with amino acids can conceivably be used to study oxidation in tail first position by enzymes, which bind natural fatty acids headfirst. Read More

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http://dx.doi.org/10.1016/j.bbalip.2018.08.012DOI Listing
November 2018

Lysophosphatidic acid triggers cathepsin B-mediated invasiveness of human endometriotic cells.

Biochim Biophys Acta Mol Cell Biol Lipids 2018 Nov 20;1863(11):1369-1377. Epub 2018 Aug 20.

Department of Obstetrics and Gynecology, Medical Faculty, Justus-Liebig-University, Feulgenstr. 12, 35392 Giessen, Germany. Electronic address:

Extracellular lysophosphatidic acid (LPA) and the G-protein-coupled LPA receptors (LPAR) are involved in cell migration and invasion and found in the human endometrium. However, underlying mechanisms resulting in cellular invasion have been rarely investigated. We used stromal endometrial T-HESC, epithelial endometriotic 12Z, 49Z and Ishikawa cells. Read More

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https://linkinghub.elsevier.com/retrieve/pii/S13881981183023
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http://dx.doi.org/10.1016/j.bbalip.2018.08.013DOI Listing
November 2018
19 Reads