Depression of the Lecithin-Cholesterol Acyltransferase Reaction in Vitamin E-Deficient Monkeys,

DTIC Science & Technology

Vitamin E deficiency in two species of monkeys reduced the esterification of cholesterol by the plasma lecithin -cholesterol acyltransferase reaction...depression in the concentration of circulating polyunsaturated fatty acid cholesteryl esters. Since the plasma lecithin -cholesterol acyltransferase...cholesterol by plasma from vitamin E-deficient monkeys is due to alteration of these sulfhydryl sites. A similar reduction in the plasma lecithin -cholesterol

Exploiting members of the BAHD acyltransferase family to synthesize multiple hydroxycinnamate and benzoate conjugates in yeast

DOE PAGES

Eudes, Aymerick; Mouille, Maxence; Robinson, David S.; ...

2016-11-21

achieved for the first time the microbial production of polyamine hydroxycinnamate amides; monolignol, malate and fatty alcohol hydroxycinnamate esters; tropane alkaloids; and benzoate/caffeate alcohol esters. In some instances, the additional expression of Flavobacterium johnsoniae tyrosine ammonia-lyase (FjTAL) allowed the synthesis of p-coumarate conjugates and eliminated the need to supplement the culture media with 4-hydroxycinnamate. In conclusion, we demonstrate in this study the effectiveness of expressing members of the plant BAHD acyltransferase family in yeast for the synthesis of numerous valuable hydroxycinnamate and benzoate conjugates.« less

Exploiting members of the BAHD acyltransferase family to synthesize multiple hydroxycinnamate and benzoate conjugates in yeast

DOE Office of Scientific and Technical Information (OSTI.GOV)

Eudes, Aymerick; Mouille, Maxence; Robinson, David S.

achieved for the first time the microbial production of polyamine hydroxycinnamate amides; monolignol, malate and fatty alcohol hydroxycinnamate esters; tropane alkaloids; and benzoate/caffeate alcohol esters. In some instances, the additional expression of Flavobacterium johnsoniae tyrosine ammonia-lyase (FjTAL) allowed the synthesis of p-coumarate conjugates and eliminated the need to supplement the culture media with 4-hydroxycinnamate. In conclusion, we demonstrate in this study the effectiveness of expressing members of the plant BAHD acyltransferase family in yeast for the synthesis of numerous valuable hydroxycinnamate and benzoate conjugates.« less

Role of Wax Ester Synthase/Acyl Coenzyme A:Diacylglycerol Acyltransferase in Oleaginous Streptomyces sp. Strain G25

PubMed Central

Röttig, Annika; Strittmatter, Carl Simon; Schauer, Jennifer; Hiessl, Sebastian; Daniel, Rolf

2016-01-01

ABSTRACT Recently, we isolated a novel Streptomyces strain which can accumulate extraordinarily large amounts of triacylglycerol (TAG) and consists of 64% fatty acids (dry weight) when cultivated with glucose and 50% fatty acids (dry weight) when cultivated with cellobiose. To identify putative gene products responsible for lipid storage and cellobiose utilization, we analyzed its draft genome sequence. A single gene encoding a wax ester synthase/acyl coenzyme A (CoA):diacylglycerol acyltransferase (WS/DGAT) was identified and heterologously expressed in Escherichia coli. The purified enzyme AtfG25 showed acyltransferase activity with C12- or C16-acyl-CoA, C12 to C18 alcohols, or dipalmitoyl glycerol. This acyltransferase exhibits 24% amino acid identity to the model enzyme AtfA from Acinetobacter baylyi but has high sequence similarities to WS/DGATs from other Streptomyces species. To investigate the impact of AtfG25 on lipid accumulation, the respective gene, atfG25, was inactivated in Streptomyces sp. strain G25. However, cells of the insertion mutant still exhibited DGAT activity and were able to store TAG, albeit in lower quantities and at lower rates than the wild-type strain. These findings clearly indicate that AtfG25 has an important, but not exclusive, role in TAG biosynthesis in the novel Streptomyces isolate and suggest the presence of alternative metabolic pathways for lipid accumulation which are discussed in the present study. IMPORTANCE A novel Streptomyces strain was isolated from desert soil, which represents an extreme environment with high temperatures, frequent drought, and nutrient scarcity. We believe that these harsh conditions promoted the development of the capacity for this strain to accumulate extraordinarily large amounts of lipids. In this study, we present the analysis of its draft genome sequence with a special focus on enzymes potentially involved in its lipid storage. Furthermore, the activity and importance of the detected

BAHD or SCPL acyltransferase? What a dilemma for acylation in the world of plant phenolic compounds.

PubMed

Bontpart, Thibaut; Cheynier, Véronique; Ageorges, Agnès; Terrier, Nancy

2015-11-01

Phenolic compounds are secondary metabolites involved in several plant growth and development processes, including resistance to biotic and abiotic stresses. The biosynthetic pathways leading to the vast diversity of plant phenolic products often include an acylation step, with phenolic compounds being the donor or acceptor molecules. To date, two acyltransferase families using phenolic compounds as acceptor or donor molecules have been described, with each using a different 'energy-rich' acyl donor. BAHD-acyltransferases, named after the first four biochemically characterized enzymes of the group, use acyl-CoA thioesters as donor molecules, whereas SCPL (Serine CarboxyPeptidase Like)-acyltransferases use 1-O-β-glucose esters. Here, common and divergent specifications found in the literature for both enzyme families were analyzed to answer the following questions. Are both acyltransferases involved in the synthesis of the same molecule (or same group of molecules)? Are both acyltransferases recruited in the same plant? How does the subcellular localization of these enzymes impact metabolite trafficking in plant cells? © 2015 INRA. New Phytologist © 2015 New Phytologist Trust.

Functional roles of three cutin biosynthetic acyltransferases in cytokinin responses and skotomorphogenesis.

PubMed

Wu, Lei; Zhou, Zhao-Yang; Zhang, Chun-Guang; Chai, Juan; Zhou, Qin; Wang, Li; Hirnerová, Eva; Mrvková, Michaela; Novák, Ondřej; Guo, Guang-Qin

2015-01-01

Cytokinins (CKs) regulate plant development and growth via a two-component signaling pathway. By forward genetic screening, we isolated an Arabidopsis mutant named grow fast on cytokinins 1 (gfc1), whose seedlings grew larger aerial parts on MS medium with CK. gfc1 is allelic to a previously reported cutin mutant defective in cuticular ridges (dcr). GFC1/DCR encodes a soluble BAHD acyltransferase (a name based on the first four enzymes characterized in this family: Benzylalcohol O-acetyltransferase, Anthocyanin O-hydroxycinnamoyltransferase, anthranilate N-hydroxycinnamoyl/benzoyltransferase and Deacetylvindoline 4-O-acetyltransferase) with diacylglycerol acyltransferase (DGAT) activity in vitro and is necessary for normal cuticle formation on epidermis in vivo. Here we show that gfc1 was a CK-insensitive mutant, as revealed by its low regeneration frequency in vitro and resistance to CK in adventitious root formation and dark-grown hypocotyl inhibition assays. In addition, gfc1 had de-etiolated phenotypes in darkness and was therefore defective in skotomorphogenesis. The background expression levels of most type-A Arabidopsis Response Regulator (ARR) genes were higher in the gfc1 mutant. The gfc1-associated phenotypes were also observed in the cutin-deficient glycerol-3-phosphate acyltransferase 4/8 (gpat4/8) double mutant [defective in glycerol-3-phosphate (G3P) acyltransferase enzymes GPAT4 and GPAT8, which redundantly catalyze the acylation of G3P by hydroxyl fatty acid (OH-FA)], but not in the cutin-deficient mutant cytochrome p450, family 86, subfamily A, polypeptide 2/aberrant induction of type three 1 (cyp86A2/att1), which affects the biosynthesis of some OH-FAs. Our results indicate that some acyltransferases associated with cutin formation are involved in CK responses and skotomorphogenesis in Arabidopsis.

Functional Roles of Three Cutin Biosynthetic Acyltransferases in Cytokinin Responses and Skotomorphogenesis

PubMed Central

Chai, Juan; Zhou, Qin; Wang, Li; Hirnerová, Eva; Mrvková, Michaela; Novák, Ondřej; Guo, Guang-Qin

2015-01-01

Cytokinins (CKs) regulate plant development and growth via a two-component signaling pathway. By forward genetic screening, we isolated an Arabidopsis mutant named grow fast on cytokinins 1 (gfc1), whose seedlings grew larger aerial parts on MS medium with CK. gfc1 is allelic to a previously reported cutin mutant defective in cuticular ridges (dcr). GFC1/DCR encodes a soluble BAHD acyltransferase (a name based on the first four enzymes characterized in this family: Benzylalcohol O-acetyltransferase, Anthocyanin O-hydroxycinnamoyltransferase, anthranilate N-hydroxycinnamoyl/benzoyltransferase and Deacetylvindoline 4-O-acetyltransferase) with diacylglycerol acyltransferase (DGAT) activity in vitro and is necessary for normal cuticle formation on epidermis in vivo. Here we show that gfc1 was a CK-insensitive mutant, as revealed by its low regeneration frequency in vitro and resistance to CK in adventitious root formation and dark-grown hypocotyl inhibition assays. In addition, gfc1 had de-etiolated phenotypes in darkness and was therefore defective in skotomorphogenesis. The background expression levels of most type-A Arabidopsis Response Regulator (ARR) genes were higher in the gfc1 mutant. The gfc1-associated phenotypes were also observed in the cutin-deficient glycerol-3-phosphate acyltransferase 4/8 (gpat4/8) double mutant [defective in glycerol-3-phosphate (G3P) acyltransferase enzymes GPAT4 and GPAT8, which redundantly catalyze the acylation of G3P by hydroxyl fatty acid (OH-FA)], but not in the cutin-deficient mutant cytochrome p450, family 86, subfamily A, polypeptide 2/aberrant induction of type three 1 (cyp86A2/att1), which affects the biosynthesis of some OH-FAs. Our results indicate that some acyltransferases associated with cutin formation are involved in CK responses and skotomorphogenesis in Arabidopsis. PMID:25803274

Expression and purification of membrane protein diacylglycerol acyltransferase

USDA-ARS?s Scientific Manuscript database

Diacylglycerol acyltransferases (DGATs) catalyze the last and rate-limiting step of triacylglycerol (TAG) biosynthesis in eukaryotic organisms. Plants and animals deficient in DGATs accumulate less TAG. Over-expression of DGATs increases TAG in seeds and other tissues. DGAT knockout mice are resista...

Evolutionary view of acyl-CoA diacylglycerol acyltransferase (DGAT), a key enzyme in neutral lipid biosynthesis.

PubMed

Turchetto-Zolet, Andreia C; Maraschin, Felipe S; de Morais, Guilherme L; Cagliari, Alexandro; Andrade, Cláudia M B; Margis-Pinheiro, Marcia; Margis, Rogerio

2011-09-20

Triacylglycerides (TAGs) are a class of neutral lipids that represent the most important storage form of energy for eukaryotic cells. DGAT (acyl-CoA: diacylglycerol acyltransferase; EC 2.3.1.20) is a transmembrane enzyme that acts in the final and committed step of TAG synthesis, and it has been proposed to be the rate-limiting enzyme in plant storage lipid accumulation. In fact, two different enzymes identified in several eukaryotic species, DGAT1 and DGAT2, are the main enzymes responsible for TAG synthesis. These enzymes do not share high DNA or protein sequence similarities, and it has been suggested that they play non-redundant roles in different tissues and in some species in TAG synthesis. Despite a number of previous studies on the DGAT1 and DGAT2 genes, which have emphasized their importance as potential obesity treatment targets to increase triacylglycerol accumulation, little is known about their evolutionary timeline in eukaryotes. The goal of this study was to examine the evolutionary relationship of the DGAT1 and DGAT2 genes across eukaryotic organisms in order to infer their origin. We have conducted a broad survey of fully sequenced genomes, including representatives of Amoebozoa, yeasts, fungi, algae, musses, plants, vertebrate and invertebrate species, for the presence of DGAT1 and DGAT2 gene homologs. We found that the DGAT1 and DGAT2 genes are nearly ubiquitous in eukaryotes and are readily identifiable in all the major eukaryotic groups and genomes examined. Phylogenetic analyses of the DGAT1 and DGAT2 amino acid sequences revealed evolutionary partitioning of the DGAT protein family into two major DGAT1 and DGAT2 clades. Protein secondary structure and hydrophobic-transmembrane analysis also showed differences between these enzymes. The analysis also revealed that the MGAT2 and AWAT genes may have arisen from DGAT2 duplication events. In this study, we identified several DGAT1 and DGAT2 homologs in eukaryote taxa. Overall, the data show that

Evolutionary view of acyl-CoA diacylglycerol acyltransferase (DGAT), a key enzyme in neutral lipid biosynthesis

PubMed Central

2011-01-01

Background Triacylglycerides (TAGs) are a class of neutral lipids that represent the most important storage form of energy for eukaryotic cells. DGAT (acyl-CoA: diacylglycerol acyltransferase; EC 2.3.1.20) is a transmembrane enzyme that acts in the final and committed step of TAG synthesis, and it has been proposed to be the rate-limiting enzyme in plant storage lipid accumulation. In fact, two different enzymes identified in several eukaryotic species, DGAT1 and DGAT2, are the main enzymes responsible for TAG synthesis. These enzymes do not share high DNA or protein sequence similarities, and it has been suggested that they play non-redundant roles in different tissues and in some species in TAG synthesis. Despite a number of previous studies on the DGAT1 and DGAT2 genes, which have emphasized their importance as potential obesity treatment targets to increase triacylglycerol accumulation, little is known about their evolutionary timeline in eukaryotes. The goal of this study was to examine the evolutionary relationship of the DGAT1 and DGAT2 genes across eukaryotic organisms in order to infer their origin. Results We have conducted a broad survey of fully sequenced genomes, including representatives of Amoebozoa, yeasts, fungi, algae, musses, plants, vertebrate and invertebrate species, for the presence of DGAT1 and DGAT2 gene homologs. We found that the DGAT1 and DGAT2 genes are nearly ubiquitous in eukaryotes and are readily identifiable in all the major eukaryotic groups and genomes examined. Phylogenetic analyses of the DGAT1 and DGAT2 amino acid sequences revealed evolutionary partitioning of the DGAT protein family into two major DGAT1 and DGAT2 clades. Protein secondary structure and hydrophobic-transmembrane analysis also showed differences between these enzymes. The analysis also revealed that the MGAT2 and AWAT genes may have arisen from DGAT2 duplication events. Conclusions In this study, we identified several DGAT1 and DGAT2 homologs in eukaryote taxa

A Plastidial Lysophosphatidic Acid Acyltransferase from Oilseed Rape1

PubMed Central

Bourgis, Fabienne; Kader, Jean-Claude; Barret, Pierre; Renard, Michel; Robinson, David; Robinson, Colin; Delseny, Michel; Roscoe, Thomas J.

1999-01-01

The biosynthesis of phosphatidic acid, a key intermediate in the biosynthesis of lipids, is controlled by lysophosphatidic acid (LPA, or 1-acyl-glycerol-3-P) acyltransferase (LPAAT, EC 2.3.1.51). We have isolated a cDNA encoding a novel LPAAT by functional complementation of the Escherichia coli mutant plsC with an immature embryo cDNA library of oilseed rape (Brassica napus). Transformation of the acyltransferase-deficient E. coli strain JC201 with the cDNA sequence BAT2 alleviated the temperature-sensitive phenotype of the plsC mutant and conferred a palmitoyl-coenzyme A-preferring acyltransferase activity to membrane fractions. The BAT2 cDNA encoded a protein of 351 amino acids with a predicted molecular mass of 38 kD and an isoelectric point of 9.7. Chloroplast-import experiments showed processing of a BAT2 precursor protein to a mature protein of approximately 32 kD, which was localized in the membrane fraction. BAT2 is encoded by a minimum of two genes that may be expressed ubiquitously. These data are consistent with the identity of BAT2 as the plastidial enzyme of the prokaryotic glycerol-3-P pathway that uses a palmitoyl-ACP to produce phosphatidic acid with a prokaryotic-type acyl composition. The homologies between the deduced protein sequence of BAT2 with prokaryotic and eukaryotic microsomal LAP acytransferases suggest that seed microsomal forms may have evolved from the plastidial enzyme. PMID:10398728

The Role of Lecithin: Retinol Acyltransferase (LRAT)-Mediated Esterification of Vitamin A in Regulating Human Breast Cancer Cell Proliferation and Differentiation

DTIC Science & Technology

2007-04-01

involved in thetranscriptional regulation of the human LRAT gene. 15. SUBJECT TERMS Breast cancer, lecithin : Retinol Acyltransferase (LRAT...R.R., Nanus, D.M., Scherr, D.S., and Gudas, L.J. 2004. Reduced lecithin : retinol acyltransferase expression correlates with increased pathologic...Solubilization and partial characterization of lecithin -retinol acyltransferase from rat liver. J Nutr Biochem 2: 503-511. Isogai, M., Chiantore, M.V., Haque

The activities of acyl-CoA:1-acyl-lysophospholipid acyltransferase(s) in human platelets.

PubMed Central

Bakken, A M; Farstad, M

1992-01-01

The activities of acyl-CoA:1-acyl-lysophospholipid acyltransferases (EC 2.3.1.23) have been studied in human platelet lysates by using endogenously formed [14C]acyl-CoA from [14C]fatty acid, ATP and CoA in the presence of 1-acyl-lysophosphatidyl-choline (lysoPC), -ethanolamine (lysoPE), -serine (lysoPS) or -inositol (lysoPI). Linoleic acid as fatty acid substrate had the highest affinity to acyl-CoA:1-acyl-lysophospholipid acyltransferase with lysoPC as variable substrate, followed by eicosapentaenoic acid (EPA) and arachidonic acid (AA). The activity at optimal conditions was 7.4, 7.3 and 7.2 nmol/min per 10(9) platelets with lysoPC as substrate, with linoleic acid, AA and EPA respectively. EPA and AA were incorporated into all lyso-forms. Linoleic acid was also incorporated into lysoPE at a high rate, but less into lysoPS and lysoPI. DHA was incorporated into lysoPC and lysoPE, but only slightly into lysoPI and lysoPS. Whereas incorporation of all fatty acids tested was maximal for lysoPC and lysoPI at 200 and 80 microM respectively, maximal incorporation needed over 500 microM for lysoPE and lysoPS. The optimal concentration for [14C]fatty acid substrates was in the range 15-150 microM for all lysophospholipids. Competition experiments with equimolar concentrations of either lysoPC and lysoPI or lysoPE resulted in formation of [14C]PC almost as if lysoPI or lysoPE were not added to the assay medium. PMID:1471991

Structure-function analysis of diacylglycerol acyltransferase sequences from 70 organisms

USDA-ARS?s Scientific Manuscript database

Diacylglycerol acyltransferases (DGATs) catalyze the final and rate-limiting step of triacylglycerol (TAG) biosynthesis in eukaryotic organisms. Understanding the roles of DGATs will help to create transgenic plants with value-added properties and provide clues for therapeutic intervention for obes...

Expression of tung tree diacylglycerol acyltransferase 1 in E. coli

USDA-ARS?s Scientific Manuscript database

Diacylglycerol acyltransferases (DGATs) catalyze the last step of triacylglycerol (TAG) biosynthesis in eukaryotic organisms. DGAT isoforms have nonredundant functions in TAG biosynthesis in species such as tung tree (Vernicia fordii) which contains 80% high-value eleostearic acid in its seed oils. ...

Expression and purification of recombinant tung tree diacylglycerol acyltransferase 2

USDA-ARS?s Scientific Manuscript database

Diacylglycerol acyltransferases (DGATs) are responsible for the last step of triacylglycerol (TAG) biosynthesis in eukaryotic organisms. Different forms of DGATs have nonredundant functions in TAG biosynthesis in species such as tung tree (Vernicia fordii), which contains approximately 80% high-valu...

Purification of recombinant tung tree diacylglycerol acyltransferases from E. coli

USDA-ARS?s Scientific Manuscript database

Understanding plant oil biosynthesis will help to create new oilseed crops with value-added properties to replace petroleum-based compounds. Diacylglycerol acyltransferases (DGATs) are key enzymes catalyzing the last step of triacylglycerol (TAG) biosynthesis in eukaryotes. Over-expression of DGATs ...

Expression and purification of recombinant tung tree diacylglycerol acyltransferase 2

USDA-ARS?s Scientific Manuscript database

Diacylglycerol acyltransferases (DGATs) catalyze the last step of triacylglycerol (TAG) biosynthesis in eukaryotic organisms. Plants and animals deficient in DGATs accumulate less TAG. Over-expression of DGATs increases TAG. DGAT knockout mice are resistant to diet-induced obesity and lack milk secr...

Phospholipase A2-treated human high-density lipoprotein and cholesterol movements: exchange processes and lecithin: cholesterol acyltransferase reactivity.

PubMed

Chollet, F; Perret, B P; Chap, H; Douste-Blazy, L

1986-02-12

Human HDL3 (d 1.125-1.21 g/ml) were treated by an exogenous phospholipase A2 from Crotalus adamenteus in the presence of albumin. Phosphatidylcholine hydrolysis ranged between 30 and 90% and the reisolated particle was essentially devoid of lipolysis products. (1) An exchange of free cholesterol was recorded between radiolabelled erythrocytes at 5-10% haematocrit and HDL3 (0.6 mM total cholesterol) from 0 to 12-15 h. Isotopic equilibration was reached. Kinetic analysis of the data indicated a constant rate of free cholesterol exchange of 13.0 microM/h with a half-time of equilibration around 3 h. Very similar values of cholesterol exchange, specific radioactivities and kinetic parameters were measured when phospholipase-treated HDL replaced control HDL. (2) The lecithin: cholesterol acyltransferase reactivity of HDL3, containing different amounts of phosphatidylcholine, as achieved by various degrees of phospholipase A2 treatment, was measured using a crude preparation of lecithin: cholesterol acyltransferase (the d 1.21-1.25 g/ml plasma fraction). The rate of esterification was determined between 0 and 12 h. Following a 15-30% lipolysis, the lecithin: cholesterol acyltransferase reactivity of HDL3 was reduced about 30-40%, and then continued to decrease, though more slowly, as the phospholipid content was further lowered in the particle. (3) The addition of the lecithin: cholesterol acyltransferase preparation into an incubation medium made of labelled erythrocytes and HDL3 promoted a movement of radioactive cholesterol out of cells, above the values of exchange, and an accumulation of cholesteryl esters in HDL. This reflected a mass consumption of free cholesterol, from both the cellular and the lipoprotein compartments upon the lecithin: cholesterol acyltransferase action. As a consequence of a decreased reactivity, phospholipase-treated HDL (with 2/3 of phosphatidylcholine hydrolyzed) proved much less effective in the lecithin: cholesterol acyltransferase

Identification of the Wax Ester Synthase/Acyl-Coenzyme A:Diacylglycerol Acyltransferase WSD1 Required for Stem Wax Ester Biosynthesis in Arabidopsis12[W][OA

PubMed Central

Li, Fengling; Wu, Xuemin; Lam, Patricia; Bird, David; Zheng, Huanquan; Samuels, Lacey; Jetter, Reinhard; Kunst, Ljerka

2008-01-01

Wax esters are neutral lipids composed of aliphatic alcohols and acids, with both moieties usually long-chain (C16 and C18) or very-long-chain (C20 and longer) carbon structures. They have diverse biological functions in bacteria, insects, mammals, and terrestrial plants and are also important substrates for a variety of industrial applications. In plants, wax esters are mostly found in the cuticles coating the primary shoot surfaces, but they also accumulate to high concentrations in the seed oils of a few plant species, including jojoba (Simmondsia chinensis), a desert shrub that is the major commercial source of these compounds. Here, we report the identification and characterization of WSD1, a member of the bifunctional wax ester synthase/diacylglycerol acyltransferase gene family, which plays a key role in wax ester synthesis in Arabidopsis (Arabidopsis thaliana) stems, as first evidenced by severely reduced wax ester levels of in the stem wax of wsd1 mutants. In vitro assays using protein extracts from Escherichia coli expressing WSD1 showed that this enzyme has a high level of wax synthase activity and approximately 10-fold lower level of diacylglycerol acyltransferase activity. Expression of the WSD1 gene in Saccharomyces cerevisiae resulted in the accumulation of wax esters, but not triacylglycerol, indicating that WSD1 predominantly functions as a wax synthase. Analyses of WSD1 expression revealed that this gene is transcribed in flowers, top parts of stems, and leaves. Fully functional yellow fluorescent protein-tagged WSD1 protein was localized to the endoplasmic reticulum, demonstrating that biosynthesis of wax esters, the final products of the alcohol-forming pathway, occurs in this subcellular compartment. PMID:18621978

Structure of a bacterial toxin-activating acyltransferase.

PubMed

Greene, Nicholas P; Crow, Allister; Hughes, Colin; Koronakis, Vassilis

2015-06-09

Secreted pore-forming toxins of pathogenic Gram-negative bacteria such as Escherichia coli hemolysin (HlyA) insert into host-cell membranes to subvert signal transduction and induce apoptosis and cell lysis. Unusually, these toxins are synthesized in an inactive form that requires posttranslational activation in the bacterial cytosol. We have previously shown that the activation mechanism is an acylation event directed by a specialized acyl-transferase that uses acyl carrier protein (ACP) to covalently link fatty acids, via an amide bond, to specific internal lysine residues of the protoxin. We now reveal the 2.15-Å resolution X-ray structure of the 172-aa ApxC, a toxin-activating acyl-transferase (TAAT) from pathogenic Actinobacillus pleuropneumoniae. This determination shows that bacterial TAATs are a structurally homologous family that, despite indiscernible sequence similarity, form a distinct branch of the Gcn5-like N-acetyl transferase (GNAT) superfamily of enzymes that typically use acyl-CoA to modify diverse bacterial, archaeal, and eukaryotic substrates. A combination of structural analysis, small angle X-ray scattering, mutagenesis, and cross-linking defined the solution state of TAATs, with intermonomer interactions mediated by an N-terminal α-helix. Superposition of ApxC with substrate-bound GNATs, and assay of toxin activation and binding of acyl-ACP and protoxin peptide substrates by mutated ApxC variants, indicates the enzyme active site to be a deep surface groove.

Two Acyltransferases Contribute Differently to Linolenic Acid Levels in Seed Oil1[OPEN

PubMed Central

Stymne, Sten

2017-01-01

Acyltransferases are key contributors to triacylglycerol (TAG) synthesis and, thus, are of great importance for seed oil quality. The effects of increased or decreased expression of ACYL-COENZYME A:DIACYLGLYCEROL ACYLTRANSFERASE1 (DGAT1) or PHOSPHOLIPID:DIACYLGLYCEROL ACYLTRANSFERASE (PDAT) on seed lipid composition were assessed in several Camelina sativa lines. Furthermore, in vitro assays of acyltransferases in microsomal fractions prepared from developing seeds of some of these lines were performed. Decreased expression of DGAT1 led to an increased percentage of 18:3n-3 without any change in total lipid content of the seed. The tri-18:3 TAG increase occurred predominantly in the cotyledon, as determined with matrix-assisted laser desorption/ionization-mass spectrometry, whereas species with two 18:3n-3 acyl groups were elevated in both cotyledon and embryonal axis. PDAT overexpression led to a relative increase of 18:2n-6 at the expense of 18:3n-3, also without affecting the total lipid content. Differential distributions of TAG species also were observed in different parts of the seed. The microsomal assays revealed that C. sativa seeds have very high activity of diacylglycerol-phosphatidylcholine interconversion. The combination of analytical and biochemical data suggests that the higher 18:2n-6 content in the seed oil of the PDAT overexpressors is due to the channeling of fatty acids from phosphatidylcholine into TAG before being desaturated to 18:3n-3, caused by the high activity of PDAT in general and by PDAT specificity for 18:2n-6. The higher levels of 18:3n-3 in DGAT1-silencing lines are likely due to the compensatory activity of a TAG-synthesizing enzyme with specificity for this acyl group and more desaturation of acyl groups occurring on phosphatidylcholine. PMID:28235891

The LINKS motif zippers trans-acyltransferase polyketide synthase assembly lines into a biosynthetic megacomplex

PubMed Central

Gay, Darren C.; Wagner, Drew T.; Meinke, Jessica L.; Zogzas, Charles E.; Gay, Glen R.; Keatinge-Clay, Adrian T.

2016-01-01

Polyketides such as the clinically-valuable antibacterial agent mupirocin are constructed by architecturally-sophisticated assembly lines known as trans-acyltransferase polyketide synthases. Organelle-sized megacomplexes composed of several copies of trans-acyltransferase polyketide synthase assembly lines have been observed by others through transmission electron microscopy to be located at the Bacillus subtilis plasma membrane, where the synthesis and export of the antibacterial polyketide bacillaene takes place. In this work we analyze ten crystal structures of trans-acyltransferase polyketide synthases ketosynthase domains, seven of which are reported here for the first time, to characterize a motif capable of zippering assembly lines into a megacomplex. While each of the three-helix LINKS (Laterally-INteracting Ketosynthase Sequence) motifs is observed to similarly dock with a spatially-reversed copy of itself through hydrophobic and ionic interactions, the amino acid sequences of this motif are not conserved. Such a code is appropriate for mediating homotypic contacts between assembly lines to ensure the ordered self-assembly of a noncovalent, yet tightly-knit, enzymatic network. LINKS-mediated lateral interactions would also have the effect of bolstering the vertical association of the polypeptides that comprise a polyketide synthase assembly line. PMID:26724270

Defective in Cuticular Ridges (DCR) of Arabidopsis thaliana, a Gene Associated with Surface Cutin Formation, Encodes a Soluble Diacylglycerol Acyltransferase*

PubMed Central

Rani, Sapa Hima; Krishna, T. H. Anantha; Saha, Saikat; Negi, Arvind Singh; Rajasekharan, Ram

2010-01-01

A key step in the triacylglycerol (TAG) biosynthetic pathway is the final acylation of diacylglycerol (DAG) by DAG acyltransferase. In silico analysis has revealed that the DCR (defective in cuticular ridges) (At5g23940) gene has a typical HX4D acyltransferase motif at the N-terminal end and a lipid binding motif VX2GF at the middle of the sequence. To understand the biochemical function, the gene was overexpressed in Escherichia coli, and the purified recombinant protein was found to acylate DAG specifically in an acyl-CoA-dependent manner. Overexpression of At5g23940 in a Saccharomyces cerevisiae quadruple mutant deficient in DAG acyltransferases resulted in TAG accumulation. At5g23940 rescued the growth of this quadruple mutant in the oleate-containing medium, whereas empty vector control did not. Lipid particles were localized in the cytosol of At5g23940-transformed quadruple mutant cells, as observed by oil red O staining. There was an incorporation of 16-hydroxyhexadecanoic acid into TAG in At5g23940-transformed cells of quadruple mutant. Here we report a soluble acyl-CoA-dependent DAG acyltransferase from Arabidopsis thaliana. Taken together, these data suggest that a broad specific DAG acyltransferase may be involved in the cutin as well as in the TAG biosynthesis by supplying hydroxy fatty acid. PMID:20921218

Defective in cuticular ridges (DCR) of Arabidopsis thaliana, a gene associated with surface cutin formation, encodes a soluble diacylglycerol acyltransferase.

PubMed

Rani, Sapa Hima; Krishna, T H Anantha; Saha, Saikat; Negi, Arvind Singh; Rajasekharan, Ram

2010-12-03

A key step in the triacylglycerol (TAG) biosynthetic pathway is the final acylation of diacylglycerol (DAG) by DAG acyltransferase. In silico analysis has revealed that the DCR (defective in cuticular ridges) (At5g23940) gene has a typical HX(4)D acyltransferase motif at the N-terminal end and a lipid binding motif VX(2)GF at the middle of the sequence. To understand the biochemical function, the gene was overexpressed in Escherichia coli, and the purified recombinant protein was found to acylate DAG specifically in an acyl-CoA-dependent manner. Overexpression of At5g23940 in a Saccharomyces cerevisiae quadruple mutant deficient in DAG acyltransferases resulted in TAG accumulation. At5g23940 rescued the growth of this quadruple mutant in the oleate-containing medium, whereas empty vector control did not. Lipid particles were localized in the cytosol of At5g23940-transformed quadruple mutant cells, as observed by oil red O staining. There was an incorporation of 16-hydroxyhexadecanoic acid into TAG in At5g23940-transformed cells of quadruple mutant. Here we report a soluble acyl-CoA-dependent DAG acyltransferase from Arabidopsis thaliana. Taken together, these data suggest that a broad specific DAG acyltransferase may be involved in the cutin as well as in the TAG biosynthesis by supplying hydroxy fatty acid.

Targeting Palmitoyl Acyltransferases in Mutant NRAS-Driven Melanoma

DTIC Science & Technology

2014-08-01

Ph.D. CONTRACTING ORGANIZATION: Massachusetts General Hospital Boston, MA 02114 REPORT DATE: August 2014 TYPE OF REPORT: Annual PREPARED...RETURN YOUR FORM TO THE ABOVE ADDRESS. 1. REPORT DATE August 2014 2. REPORT TYPE Annual 3. DATES COVERED 1 Aug 2013 - 31 Jul 2014 4. TITLE AND...lysophosphatidylcholine acyltransferase 2 0 25 2 4 COMT catechol O-methyltransferase 2 24 16 8 HEATR3 HEAT repeat-containing protein 3 0 21 6 1 ZDHHC20 probable

The LINKS motif zippers trans-acyltransferase polyketide synthase assembly lines into a biosynthetic megacomplex.

PubMed

Gay, Darren C; Wagner, Drew T; Meinke, Jessica L; Zogzas, Charles E; Gay, Glen R; Keatinge-Clay, Adrian T

2016-03-01

Polyketides such as the clinically-valuable antibacterial agent mupirocin are constructed by architecturally-sophisticated assembly lines known as trans-acyltransferase polyketide synthases. Organelle-sized megacomplexes composed of several copies of trans-acyltransferase polyketide synthase assembly lines have been observed by others through transmission electron microscopy to be located at the Bacillus subtilis plasma membrane, where the synthesis and export of the antibacterial polyketide bacillaene takes place. In this work we analyze ten crystal structures of trans-acyltransferase polyketide synthases ketosynthase domains, seven of which are reported here for the first time, to characterize a motif capable of zippering assembly lines into a megacomplex. While each of the three-helix LINKS (Laterally-INteracting Ketosynthase Sequence) motifs is observed to similarly dock with a spatially-reversed copy of itself through hydrophobic and ionic interactions, the amino acid sequences of this motif are not conserved. Such a code is appropriate for mediating homotypic contacts between assembly lines to ensure the ordered self-assembly of a noncovalent, yet tightly-knit, enzymatic network. LINKS-mediated lateral interactions would also have the effect of bolstering the vertical association of the polypeptides that comprise a polyketide synthase assembly line. Copyright © 2015 Elsevier Inc. All rights reserved.

Soybean oil biosynthesis: role of diacylglycerol acyltransferases.

PubMed

Li, Runzhi; Hatanaka, Tomoko; Yu, Keshun; Wu, Yongmei; Fukushige, Hirotada; Hildebrand, David

2013-03-01

Diacylglycerol acyltransferase (DGAT) catalyzes the acyl-CoA-dependent acylation of sn-1,2-diacylglycerol to form seed oil triacylglycerol (TAG). To understand the features of genes encoding soybean (Glycine max) DGATs and possible roles in soybean seed oil synthesis and accumulation, two full-length cDNAs encoding type 1 diacylglycerol acyltransferases (GmDGAT1A and GmDGAT1B) were cloned from developing soybean seeds. These coding sequences share identities of 94 % and 95 % in protein and DNA sequences. The genomic architectures of GmDGAT1A and GmDGAT1B both contain 15 introns and 16 exons. Differences in the lengths of the first exon and most of the introns were found between GmDGAT1A and GmDGAT1B genomic sequences. Furthermore, detailed in silico analysis revealed a third predicted DGAT1, GmDGAT1C. GmDGAT1A and GmDGAT1B were found to have similar activity levels and substrate specificities. Oleoyl-CoA and sn-1,2-diacylglycerol were preferred substrates over vernoloyl-CoA and sn-1,2-divernoloylglycerol. Both transcripts are much more abundant in developing seeds than in other tissues including leaves, stem, roots, and flowers. Both soybean DGAT1A and DGAT1B are highly expressed at developing seed stages of maximal TAG accumulation with DGAT1B showing highest expression at somewhat later stages than DGAT1A. DGAT1A and DGAT1B show expression profiles consistent with important roles in soybean seed oil biosynthesis and accumulation.

Expression of tung seed diacylglycerol acyltransferases (DGAT) in E. coli and yeast

USDA-ARS?s Scientific Manuscript database

Diacylglycerol acyltransferases (DGATs) catalyze the last step of triacylglycerol (TAG) biosynthesis in eukaryotic organisms. Plants and animals deficient in DGATs accumulate less TAG, resist obesity, and/or lack milk secretion. Over-expression of the DGATs increases TAG content in seeds and other t...

Technical note: Improving the AWAT filter with interpolation schemes for advanced processing of high resolution data

NASA Astrophysics Data System (ADS)

Peters, Andre; Nehls, Thomas; Wessolek, Gerd

2016-06-01

Weighing lysimeters with appropriate data filtering yield the most precise and unbiased information for precipitation (P) and evapotranspiration (ET). A recently introduced filter scheme for such data is the AWAT (Adaptive Window and Adaptive Threshold) filter (Peters et al., 2014). The filter applies an adaptive threshold to separate significant from insignificant mass changes, guaranteeing that P and ET are not overestimated, and uses a step interpolation between the significant mass changes. In this contribution we show that the step interpolation scheme, which reflects the resolution of the measuring system, can lead to unrealistic prediction of P and ET, especially if they are required in high temporal resolution. We introduce linear and spline interpolation schemes to overcome these problems. To guarantee that medium to strong precipitation events abruptly following low or zero fluxes are not smoothed in an unfavourable way, a simple heuristic selection criterion is used, which attributes such precipitations to the step interpolation. The three interpolation schemes (step, linear and spline) are tested and compared using a data set from a grass-reference lysimeter with 1 min resolution, ranging from 1 January to 5 August 2014. The selected output resolutions for P and ET prediction are 1 day, 1 h and 10 min. As expected, the step scheme yielded reasonable flux rates only for a resolution of 1 day, whereas the other two schemes are well able to yield reasonable results for any resolution. The spline scheme returned slightly better results than the linear scheme concerning the differences between filtered values and raw data. Moreover, this scheme allows continuous differentiability of filtered data so that any output resolution for the fluxes is sound. Since computational burden is not problematic for any of the interpolation schemes, we suggest always using the spline scheme.

Developmental regulation of diacylglycerol acyltransferase family gene expression in tung tree tissues

USDA-ARS?s Scientific Manuscript database

Diacylglycerol acyltransferases (DGAT) are responsible for the final and rate-limiting step of triacylglycerol (TAG) biosynthesis in eukaryotic organisms. DGAT genes have been identified in numerous organisms. Multiple isoforms of DGAT are present in eukaryotes, including DGAT1 and DGAT2 of tung tre...

Comparison of human plasma low- and high-density lipoproteins as substrates for lecithin: cholesterol acyltransferase.

PubMed

Barter, P J; Hopkins, G J; Gorjatschko, L

1984-01-17

A recent observation that lecithin: cholesterol acyltransferase (EC 2.3.1.43) interacts with both low-density lipoproteins (LDL) and high-density lipoproteins (HDL) in human plasma is in apparent conflict with an earlier finding that the purified enzyme, while highly reactive with isolated HDL, was only minimally reactive with LDL. There is evidence, however, that lecithin: cholesterol acyltransferase may exist physiologically as a component of a complex with other proteins and that studies with the isolated enzyme may therefore provide misleading results. Consequently, interactions of the enzyme with isolated human lipoproteins have been re-examined in incubations containing lecithin: cholesterol acyltransferase as a component of human lipoprotein-free plasma in which a physiologically active complex of the enzyme with other proteins may have been preserved. In this system there was a ready esterification of the free cholesterol associated with both LDL and HDL-subfraction 3 (HDL3) in reactions that obeyed typical enzyme-saturation kinetics. For a given preparation of lipoprotein-free plasma the Vmax values with LDL and with HDL3 were virtually identical. The apparent Km for free cholesterol associated with HDL3 was 5.6 X 10(-5) M, while for that associated with LDL it was 4.1 X 10(-4) M. This implied that, in terms of free cholesterol concentration, the affinity of HDL3 for lecithin: cholesterol acyltransferase was about 7-times greater than that of LDL. When expressed in terms of lipoprotein particle concentration, however, it was apparent that the affinity of LDL for the enzyme was considerably greater than that of HDL3. When the lipoprotein fractions were equated in terms of lipoprotein surface area, the apparent affinities of the two fractions for the enzyme were found to be comparable.

Activities of acyl-CoA:diacylglycerol acyltransferase (DGAT) and phospholipid:diacylglycerol acyltransferase (PDAT) in microsomal preparations of developing sunflower and safflower seeds.

PubMed

Banaś, Walentyna; Sanchez Garcia, Alicia; Banaś, Antoni; Stymne, Sten

2013-06-01

The last step in triacylglycerols (TAG) biosynthesis in oil seeds, the acylation of diacylglycerols (DAG), is catalysed by two types of enzymes: the acyl-CoA:diacylglycerol acyltransferase (DGAT) and phospholipid:diacylglycerol acyltransferase (PDAT). The relative contribution of these enzymes in the synthesis of TAG has not yet been defined in any plant tissue. In the presented work, microsomal preparations were obtained from sunflower and safflower seeds at different stages of development and used in DGAT and PDAT enzyme assays. The ratio between PDAT and DGAT activity differed dramatically between the two different species. DGAT activities were measured with two different acyl acceptors and assay methods using two different acyl-CoAs, and in all cases the ratio of PDAT to DGAT activity was significantly higher in safflower than sunflower. The sunflower DGAT, measured by both methods, showed significant higher activity with 18:2-CoA than with 18:1-CoA, whereas the opposite specificity was seen with the safflower enzyme. The specificities of PDAT on the other hand, were similar in both species with 18:2-phosphatidylcholine being a better acyl donor than 18:1-PC and with acyl groups at the sn-2 position utilised about fourfold the rate of the sn-1 position. No DAG:DAG transacylase activity could be detected in the microsomal preparations.

Structure-function analysis of diacylglycerol acyltransferase sequences for metabolic engineering and drug discovery

USDA-ARS?s Scientific Manuscript database

Diacylglycerol acyltransferase families (DGATs) catalyze the final and rate-limiting step of triacylglycerol (TAG) biosynthesis in eukaryotic organisms. DGAT knockout mice are resistant to diet-induced obesity and lack milk secretion. Over-expression of DGATs increases TAG in plants. Therefore, unde...

Overexpression of human diacylglycerol acyltransferase 1, acyl-coa:cholesterol acyltransferase 1, or acyl-CoA:cholesterol acyltransferase 2 stimulates secretion of apolipoprotein B-containing lipoproteins in McA-RH7777 cells.

PubMed

Liang, John J; Oelkers, Peter; Guo, Cuiying; Chu, Pi-Chun; Dixon, Joseph L; Ginsberg, Henry N; Sturley, Stephen L

2004-10-22

The relative importance of each core lipid in the assembly and secretion of very low density lipoproteins (VLDL) has been of interest over the past decade. The isolation of genes encoding diacylglycerol acyltransferase (DGAT) and acyl-CoA:cholesterol acyltransferases (ACAT1 and ACAT2) provided the opportunity to investigate the effects of isolated increases in triglycerides (TG) or cholesteryl esters (CE) on apolipoprotein B (apoB) lipoprotein biogenesis. Overexpression of human DGAT1 in rat hepatoma McA-RH7777 cells resulted in increased synthesis, cellular accumulation, and secretion of TG. These effects were associated with decreased intracellular degradation and increased secretion of newly synthesized apoB as VLDL. Similarly, overexpression of human ACAT1 or ACAT2 in McA-RH7777 cells resulted in increased synthesis, cellular accumulation, and secretion of CE. This led to decreased intracellular degradation and increased secretion of VLDL apoB. Overexpression of ACAT2 had a significantly greater impact upon assembly and secretion of VLDL from liver cells than did overexpression of ACAT1. The addition of oleic acid (OA) to media resulted in a further increase in VLDL secretion from cells expressing DGAT1, ACAT1, or ACAT2. VLDL secreted from DGAT1-expressing cells incubated in OA had a higher TG:CE ratio than VLDL secreted from ACAT1- and ACAT2-expressing cells treated with OA. These studies indicate that increasing DGAT1, ACAT1, or ACAT2 expression in McA-RH7777 cells stimulates the assembly and secretion of VLDL from liver cells and that the core composition of the secreted VLDL reflects the enzymatic activity that is elevated.

Leishmania dihydroxyacetonephosphate acyltransferase LmDAT is important for ether lipid biosynthesis but not for the integrity of detergent resistant membranes.

PubMed

Zufferey, Rachel; Al-Ani, Gada K; Dunlap, Kara

2009-12-01

Glycerolipid biosynthesis in Leishmania initiates with the acylation of glycerol-3-phosphate by a single glycerol-3-phosphate acyltransferase, LmGAT, or of dihydroxyacetonephosphate by a dihydroxyacetonephosphate acyltransferase, LmDAT. We previously reported that acylation of the precursor dihydroxyacetonephosphate rather than glycerol-3-phosphate is the physiologically relevant pathway for Leishmania parasites. We demonstrated that LmDAT is important for normal growth, survival during the stationary phase, and for virulence. Here, we assessed the role of LmDAT in glycerolipid metabolism and metacyclogenesis. LmDAT was found to be implicated in the biosynthesis of ether glycerolipids, including the ether lipid derived virulence factor lipophosphoglycan and glycosylphosphatidylinositol-anchored proteins. The null mutant produced longer lipophosphoglycan molecules that were not released in the medium, and augmented levels of glycosylphosphatidylinositol-anchored proteins. In addition, the integrity of detergent resistant membranes was not affected by the absence of the LmDAT gene. Further, our genetic analyses strongly suggest that LmDAT was synthetic lethal with the glycerol-3-phosphate acyltransferase encoding gene LmGAT, implying that Leishmania expresses only two acyltransferases that initiate the biosynthesis of its cellular glycerolipids. Last, despite the fact that LmDAT is important for virulence the null mutant still exhibited the typical characteristics of metacyclics.

Structural and Functional Studies of a Pyran Synthase Domain from a trans-Acyltransferase Assembly Line.

PubMed

Wagner, Drew T; Zhang, Zhicheng; Meoded, Roy A; Cepeda, Alexis J; Piel, Jörn; Keatinge-Clay, Adrian T

2018-04-20

trans-Acyltransferase assembly lines possess enzymatic domains often not observed in their better characterized cis-acyltransferase counterparts. Within this repertoire of largely unexplored biosynthetic machinery is a class of enzymes called the pyran synthases that catalyze the formation of five- and six-membered cyclic ethers from diverse polyketide chains. The 1.55 Å resolution crystal structure of a pyran synthase domain excised from the ninth module of the sorangicin assembly line highlights the similarity of this enzyme to the ubiquitous dehydratase domain and provides insight into the mechanism of ring formation. Functional assays of point mutants reveal the central importance of the active site histidine that is shared with the dehydratases as well as the supporting role of a neighboring semiconserved asparagine.

A two-helix motif positions the active site of lysophosphatidic acid acyltransferase for catalysis within the membrane bilayer

PubMed Central

Robertson, Rosanna M.; Yao, Jiangwei; Gajewski, Stefan; Kumar, Gyanendra; Martin, Erik W.; Rock, Charles O.; White, Stephen W.

2017-01-01

Phosphatidic acid is the central intermediate in membrane phospholipid synthesis and is generated by two acyltransferases in a pathway conserved in all life forms. The second step in this pathway is catalyzed by 1-acyl-sn-glycero-3-phosphate acyltransferase, called PlsC in bacteria. The crystal structure of PlsC from Thermotoga maritima reveals an unusual hydrophobic/aromatic N-terminal two-helix motif linked to an acyltransferase αβ domain that contains the catalytic HX4D motif. PlsC dictates the acyl chain composition of the 2-position of phospholipids, and the acyl chain selectivity ‘ruler’ is an appropriately placed and closed hydrophobic tunnel. This was confirmed by site-directed mutagenesis and membrane composition analysis of Escherichia coli cells expressing the mutated proteins. MD simulations reveal that the two-helix motif represents a novel substructure that firmly anchors the protein to one leaflet of the membrane. This binding mode allows the PlsC active site to acylate lysophospholipids within the membrane bilayer using soluble acyl donors. PMID:28714993

Involvement of an octose ketoreductase and two acyltransferases in the biosynthesis of paulomycins

NASA Astrophysics Data System (ADS)

Li, Jine; Wang, Min; Ding, Yong; Tang, Yue; Zhang, Zhiguo; Chen, Yihua

2016-02-01

C-4 hydroxyethyl branched octoses have been observed in polysaccharides of several genera of gram negative bacteria and in various antibiotics produced by gram positive bacteria. The C-4 hydroxyethyl branch was proposed to be converted from C-4 acetyl branch by an uncharacterized ketoreduction step. Paulomycins (PAUs) are glycosylated antibiotics with potent inhibitory activity against gram positive bacteria and are structurally defined by its unique C-4‧ hydroxyethyl branched paulomycose moiety. A novel aldo-keto-reductase, Pau7 was characterized as the enzyme catalyzing the stereospecific ketoreduction of 7‧-keto of PAU E (1) to give the C-4‧ hydroxyethyl branched paulomycose moiety of PAU F (2). An acyltransferase Pau6 further decorates the C-4‧ hydroxyethyl branch of paulomycose moiety of 2 by attaching various fatty acyl chains to 7‧-OH to generate diverse PAUs. In addition, another acyltransferase Pau24 was proposed to be responsible for the 13-O-acetylation of PAUs.

Molecular pathways in the transformation of model discoidal lipoprotein complexes induced by lecithin:cholesterol acyltransferase.

PubMed

Nichols, A V; Blanche, P J; Gong, E L; Shore, V G; Forte, T M

1985-05-17

Incubation (24 h, 37 degrees C) of discoidal complexes of phosphatidylcholine and apolipoprotein A-I (molar ratio 95 +/- 10 egg yolk phosphatidylcholine-apolipoprotein A-I; 10.5 X 4.0 nm, long X short dimension; designated, class 3 complexes) with the ultracentrifugal d greater than 1.21 g/ml fraction transformed the discoidal complexes to a small product with apparent mean hydrated and nonhydrated diameter of 7.8 and 6.6 nm, respectively. Formation of the small product was associated with marked reduction in phosphatidylcholine-apolipoprotein AI molar ratio of the complexes (on average from 95:1 to 45:1). Phospholipase A2 activity of lecithin:cholesterol acyltransferase participated in the depletion process, as evidenced by production of unesterified fatty acids. In the presence of the d greater than 1.21 g/ml fraction or partially purified lecithin:cholesterol acyltransferase and a source of unesterified cholesterol, the small product could be transformed to a core-containing (cholesteryl ester) round product with a hydrated and nonhydrated diameter of 8.6 and 7.5 nm, respectively. By means of cross-linking with dimethylsuberimidate, the protein moiety of the small product was shown to contain primarily two apolipoprotein A-I molecules per particle, while the large product contained three apolipoprotein A-I molecules per particle. The increase in number of apolipoprotein A-I molecules per particle during transformation of the small to the large product appeared to result from fusion of the small particles during core build-up and release of excess apolipoprotein A-I from the fusion product. The results obtained with the model complexes were consistent for the most part with recent observations (Chen, C., Applegate, K., King, W.C., Glomset, J.A., Norum, K.R. and Gjone, E. (1984) J. Lipid Res. 25, 269-282) on the transformation, by lecithin:cholesterol acyltransferase, of the small spherical high-density lipoproteins of patients with familial lecithin

Generation of N-Acylphosphatidylethanolamine by Members of the Phospholipase A/Acyltransferase (PLA/AT) Family*

PubMed Central

Uyama, Toru; Ikematsu, Natsuki; Inoue, Manami; Shinohara, Naoki; Jin, Xing-Hua; Tsuboi, Kazuhito; Tonai, Takeharu; Tokumura, Akira; Ueda, Natsuo

2012-01-01

Bioactive N-acylethanolamines (NAEs), including N-palmitoylethanolamine, N-oleoylethanolamine, and N-arachidonoylethanolamine (anandamide), are formed from membrane glycerophospholipids in animal tissues. The pathway is initiated by N-acylation of phosphatidylethanolamine to form N-acylphosphatidylethanolamine (NAPE). Despite the physiological importance of this reaction, the enzyme responsible, N-acyltransferase, remains molecularly uncharacterized. We recently demonstrated that all five members of the HRAS-like suppressor tumor family are phospholipid-metabolizing enzymes with N-acyltransferase activity and are renamed HRASLS1–5 as phospholipase A/acyltransferase (PLA/AT)-1–5. However, it was poorly understood whether these proteins were involved in the formation of NAPE in living cells. In the present studies, we first show that COS-7 cells transiently expressing recombinant PLA/AT-1, -2, -4, or -5, and HEK293 cells stably expressing PLA/AT-2 generated significant amounts of [14C]NAPE and [14C]NAE when cells were metabolically labeled with [14C]ethanolamine. Second, as analyzed by liquid chromatography-tandem mass spectrometry, the stable expression of PLA/AT-2 in cells remarkably increased endogenous levels of NAPEs and NAEs with various N-acyl species. Third, when NAPE-hydrolyzing phospholipase D was additionally expressed in PLA/AT-2-expressing cells, accumulating NAPE was efficiently converted to NAE. We also found that PLA/AT-2 was partly responsible for NAPE formation in HeLa cells that endogenously express PLA/AT-2. These results suggest that PLA/AT family proteins may produce NAPEs serving as precursors of bioactive NAEs in vivo. PMID:22825852

A Land-Plant-Specific Glycerol-3-Phosphate Acyltransferase Family in Arabidopsis: Substrate Specificity, sn-2 Preference, and Evolution1[W][OA

PubMed Central

Yang, Weili; Simpson, Jeffrey P.; Li-Beisson, Yonghua; Beisson, Fred; Pollard, Mike; Ohlrogge, John B.

2012-01-01

Arabidopsis (Arabidopsis thaliana) has eight glycerol-3-phosphate acyltransferase (GPAT) genes that are members of a plant-specific family with three distinct clades. Several of these GPATs are required for the synthesis of cutin or suberin. Unlike GPATs with sn-1 regiospecificity involved in membrane or storage lipid synthesis, GPAT4 and -6 are unique bifunctional enzymes with both sn-2 acyltransferase and phosphatase activity resulting in 2-monoacylglycerol products. We present enzymology, pathway organization, and evolutionary analysis of this GPAT family. Within the cutin-associated clade, GPAT8 is demonstrated as a bifunctional sn-2 acyltransferase/phosphatase. GPAT4, -6, and -8 strongly prefer C16:0 and C18:1 ω-oxidized acyl-coenzyme As (CoAs) over unmodified or longer acyl chain substrates. In contrast, suberin-associated GPAT5 can accommodate a broad chain length range of ω-oxidized and unsubstituted acyl-CoAs. These substrate specificities (1) strongly support polyester biosynthetic pathways in which acyl transfer to glycerol occurs after oxidation of the acyl group, (2) implicate GPAT specificities as one major determinant of cutin and suberin composition, and (3) argue against a role of sn-2-GPATs (Enzyme Commission 2.3.1.198) in membrane/storage lipid synthesis. Evidence is presented that GPAT7 is induced by wounding, produces suberin-like monomers when overexpressed, and likely functions in suberin biosynthesis. Within the third clade, we demonstrate that GPAT1 possesses sn-2 acyltransferase but not phosphatase activity and can utilize dicarboxylic acyl-CoA substrates. Thus, sn-2 acyltransferase activity extends to all subbranches of the Arabidopsis GPAT family. Phylogenetic analyses of this family indicate that GPAT4/6/8 arose early in land-plant evolution (bryophytes), whereas the phosphatase-minus GPAT1 to -3 and GPAT5/7 clades diverged later with the appearance of tracheophytes. PMID:22864585

Structure-function analysis of diacylglycerol acyltransferase sequences from tung tree and 82 other Organisms

USDA-ARS?s Scientific Manuscript database

Diacylglycerol acyltransferase family (DGATs) catalyzes the final and rate-limiting step of triacylglycerol (TAG) biosynthesis in eukaryotic organisms. DGATs esterify sn-1,2-diacylglycerol with a long-chain fatty acyl-CoA. Understanding the roles of DGATs will help to create transgenic plants with v...

Variant amino acid residues alter the enzyme activity of peanut type 2 Diacylglycerol Acyltransferases

USDA-ARS?s Scientific Manuscript database

Diacylglycerol acyltransferase (DGAT) catalyzes the final, rate-limiting step in triacylglycerol (TAG) biosynthesis via the acyl-CoA-dependent acylation of diacylglycerol. In this study, type-2 DGAT2 genes were cloned from eleven peanut cultivars. Sequence analysis revealed at least eight peanut D...

Understanding the role of histidine in the GHSxG acyltransferase active site motif: Evidence for histidine stabilization of the malonyl-enzyme intermediate

DOE Office of Scientific and Technical Information (OSTI.GOV)

Poust, Sean; Yoon, Isu; Adams, Paul D.

Acyltransferases determine which extender units are incorporated into polyketide and fatty acid products. Thus, the ping-pong acyltransferase mechanism utilizes a serine in a conserved GHSxG motif. However, the role of the conserved histidine in this motif is poorly understood. We observed that a histidine to alanine mutation (H640A) in the GHSxG motif of the malonyl-CoA specific yersiniabactin acyltransferase results in an approximately seven-fold higher hydrolysis rate over the wildtype enzyme, while retaining transacylation activity. We propose two possibilities for the reduction in hydrolysis rate: either H640 structurally stabilizes the protein by hydrogen bonding with a conserved asparagine in the ferredoxin-likemore » subdomain of the protein, or a water-mediated hydrogen bond between H640 and the malonyl moiety stabilizes the malonyl-O-AT ester intermediate.« less

Understanding the role of histidine in the GHSxG acyltransferase active site motif: Evidence for histidine stabilization of the malonyl-enzyme intermediate

DOE PAGES

Poust, Sean; Yoon, Isu; Adams, Paul D.; ...

2014-10-06

Acyltransferases determine which extender units are incorporated into polyketide and fatty acid products. Thus, the ping-pong acyltransferase mechanism utilizes a serine in a conserved GHSxG motif. However, the role of the conserved histidine in this motif is poorly understood. We observed that a histidine to alanine mutation (H640A) in the GHSxG motif of the malonyl-CoA specific yersiniabactin acyltransferase results in an approximately seven-fold higher hydrolysis rate over the wildtype enzyme, while retaining transacylation activity. We propose two possibilities for the reduction in hydrolysis rate: either H640 structurally stabilizes the protein by hydrogen bonding with a conserved asparagine in the ferredoxin-likemore » subdomain of the protein, or a water-mediated hydrogen bond between H640 and the malonyl moiety stabilizes the malonyl-O-AT ester intermediate.« less

Requirement of catalytic-triad and related amino acids for the acyltransferase activity of Tanacetum cinerariifolium GDSL lipase/esterase TcGLIP for ester-bond formation in pyrethrin biosynthesis.

PubMed

Kikuta, Yukio; Yamada, Gen; Mitsumori, Tomonori; Takeuchi, Takayuki; Nakayama, Koji; Katsuda, Yoshio; Hatanaka, Akikazu; Matsuda, Kazuhiko

2013-01-01

We have recently discovered that a GDSL lipase/esterase (TcGLIP) in Tanacetum cinerariifolium catalyzed acyltransferase activity to form an ester bond in the natural insecticide, pyrethrin. TcGLIP contained Ser40 in Block I, Gly64 in Block II, Asn168 in Block III and Asp318 and His321 in Block V, suggesting underlying hydrolase activity, although little is known about their role in acyltransferase activity. We expressed TcGLIP here in Esherichia coli as a fusion with maltose-binding protein (MBP), part of the fusion being cleaved with a protease to obtain MBP-free TcGLIP. A kinetic analysis revealed that the MBP moiety scarcely influenced the kinetic parameters. The effects on acyltransferase activity of mutations of Gly64, Asn168, Asp318 and His321 were investigated by using MBP-fused TcGLIP. Mutations of these amino acids markedly reduced the acyltransferase activity, suggesting their critical role in the production of pyrethrins.

ATP-binding cassette transporters and sterol O-acyltransferases interact at membrane microdomains to modulate sterol uptake and esterification

PubMed Central

Gulati, Sonia; Balderes, Dina; Kim, Christine; Guo, Zhongmin A.; Wilcox, Lisa; Area-Gomez, Estela; Snider, Jamie; Wolinski, Heimo; Stagljar, Igor; Granato, Juliana T.; Ruggles, Kelly V.; DeGiorgis, Joseph A.; Kohlwein, Sepp D.; Schon, Eric A.; Sturley, Stephen L.

2015-01-01

A key component of eukaryotic lipid homeostasis is the esterification of sterols with fatty acids by sterol O-acyltransferases (SOATs). The esterification reactions are allosterically activated by their sterol substrates, the majority of which accumulate at the plasma membrane. We demonstrate that in yeast, sterol transport from the plasma membrane to the site of esterification is associated with the physical interaction of the major SOAT, acyl-coenzyme A:cholesterol acyltransferase (ACAT)-related enzyme (Are)2p, with 2 plasma membrane ATP-binding cassette (ABC) transporters: Aus1p and Pdr11p. Are2p, Aus1p, and Pdr11p, unlike the minor acyltransferase, Are1p, colocalize to sterol and sphingolipid-enriched, detergent-resistant microdomains (DRMs). Deletion of either ABC transporter results in Are2p relocalization to detergent-soluble membrane domains and a significant decrease (53–36%) in esterification of exogenous sterol. Similarly, in murine tissues, the SOAT1/Acat1 enzyme and activity localize to DRMs. This subcellular localization is diminished upon deletion of murine ABC transporters, such as Abcg1, which itself is DRM associated. We propose that the close proximity of sterol esterification and transport proteins to each other combined with their residence in lipid-enriched membrane microdomains facilitates rapid, high-capacity sterol transport and esterification, obviating any requirement for soluble intermediary proteins.—Gulati, S., Balderes, D., Kim, C., Guo, Z. A., Wilcox, L., Area-Gomez, E., Snider, J., Wolinski, H., Stagljar, I., Granato, J. T., Ruggles, K. V., DeGiorgis, J. A., Kohlwein, S. D., Schon, E. A., Sturley, S. L. ATP-binding cassette transporters and sterol O-acyltransferases interact at membrane microdomains to modulate sterol uptake and esterification. PMID:26220175

Architectural Organization of the Metabolic Regulatory Enzyme Ghrelin O-Acyltransferase*

PubMed Central

Taylor, Martin S.; Ruch, Travis R.; Hsiao, Po-Yuan; Hwang, Yousang; Zhang, Pingfeng; Dai, Lixin; Huang, Cheng Ran Lisa; Berndsen, Christopher E.; Kim, Min-Sik; Pandey, Akhilesh; Wolberger, Cynthia; Marmorstein, Ronen; Machamer, Carolyn; Boeke, Jef D.; Cole, Philip A.

2013-01-01

Ghrelin O-acyltransferase (GOAT) is a polytopic integral membrane protein required for activation of ghrelin, a secreted metabolism-regulating peptide hormone. Although GOAT is a potential therapeutic target for the treatment of obesity and diabetes and plays a key role in other physiologic processes, little is known about its structure or mechanism. GOAT is a member of the membrane-bound O-acyltransferase (MBOAT) family, a group of polytopic integral membrane proteins involved in lipid-biosynthetic and lipid-signaling reactions from prokaryotes to humans. Here we use phylogeny and a variety of bioinformatic tools to predict the topology of GOAT. Using selective permeabilization indirect immunofluorescence microscopy in combination with glycosylation shift immunoblotting, we demonstrate that GOAT contains 11 transmembrane helices and one reentrant loop. Development of the V5Glyc tag, a novel, small, and sensitive dual topology reporter, facilitated these experiments. The MBOAT family invariant residue His-338 is in the ER lumen, consistent with other family members, but conserved Asn-307 is cytosolic, making it unlikely that both are involved in catalysis. Photocross-linking of synthetic ghrelin analogs and inhibitors demonstrates binding to the C-terminal region of GOAT, consistent with a role of His-338 in the active site. This knowledge of GOAT architecture is important for a deeper understanding of the mechanism of GOAT and other MBOATs and could ultimately advance the discovery of selective inhibitors for these enzymes. PMID:24045953

Architectural organization of the metabolic regulatory enzyme ghrelin O-acyltransferase.

PubMed

Taylor, Martin S; Ruch, Travis R; Hsiao, Po-Yuan; Hwang, Yousang; Zhang, Pingfeng; Dai, Lixin; Huang, Cheng Ran Lisa; Berndsen, Christopher E; Kim, Min-Sik; Pandey, Akhilesh; Wolberger, Cynthia; Marmorstein, Ronen; Machamer, Carolyn; Boeke, Jef D; Cole, Philip A

2013-11-08

Ghrelin O-acyltransferase (GOAT) is a polytopic integral membrane protein required for activation of ghrelin, a secreted metabolism-regulating peptide hormone. Although GOAT is a potential therapeutic target for the treatment of obesity and diabetes and plays a key role in other physiologic processes, little is known about its structure or mechanism. GOAT is a member of the membrane-bound O-acyltransferase (MBOAT) family, a group of polytopic integral membrane proteins involved in lipid-biosynthetic and lipid-signaling reactions from prokaryotes to humans. Here we use phylogeny and a variety of bioinformatic tools to predict the topology of GOAT. Using selective permeabilization indirect immunofluorescence microscopy in combination with glycosylation shift immunoblotting, we demonstrate that GOAT contains 11 transmembrane helices and one reentrant loop. Development of the V5Glyc tag, a novel, small, and sensitive dual topology reporter, facilitated these experiments. The MBOAT family invariant residue His-338 is in the ER lumen, consistent with other family members, but conserved Asn-307 is cytosolic, making it unlikely that both are involved in catalysis. Photocross-linking of synthetic ghrelin analogs and inhibitors demonstrates binding to the C-terminal region of GOAT, consistent with a role of His-338 in the active site. This knowledge of GOAT architecture is important for a deeper understanding of the mechanism of GOAT and other MBOATs and could ultimately advance the discovery of selective inhibitors for these enzymes.

Plant acyl-CoA:lysophosphatidylcholine acyltransferases (LPCATs) have different specificities in their forward and reverse reactions

USDA-ARS?s Scientific Manuscript database

Acyl-CoA:lysophosphatidylcholine acyltransferase (LPCAT) enzymes have central roles inacyl editing of phosphatidylcholine (PC). Plant LPCAT genes were expressed in yeast and characterized biochemically in microsomal preparations of the cells. Specificities for different acyl-CoAs were similar for se...

High-density lipoprotein cholesterol subfractions and lecithin: cholesterol acyltransferase activity in collegiate soccer players.

PubMed

Imamura, H; Nagata, A; Oshikata, R; Yoshimura, Y; Miyamoto, N; Miyahara, K; Oda, K; Iide, K

2013-05-01

Many of the published data on the lipid profile of athletes is based on studies of endurance athletes. The data on soccer players are rare. The purpose of this study was to examine serum high-density lipoprotein cholesterol subfractions and lecithin:cholesterol acyltransferase activity in collegiate soccer players. 31 well-trained male collegiate soccer players were divided into 2 groups: 16 defenders and 15 offenders. They were compared with 16 sedentary controls. Dietary information was obtained with a food frequency questionnaire. The subjects were all non-smokers and were not taking any drug known to affect the lipid and lipoprotein metabolism. The offenders had significantly higher high-density lipoprotein cholesterol, high-density lipoprotein2 cholesterol, and apolipoprotein A-I than the defenders and controls, whereas the defenders had the significantly higher high-density lipoprotein2 cholesterol than the controls. Both groups of athletes had significantly higher lecithin:cholesterol acyltransferase activity than the controls. The results indicate that favorable lipid and lipoprotein profile could be obtained by vigorous soccer training. © Georg Thieme Verlag KG Stuttgart · New York.

Identification of acyltransferases required for cutin biosynthesis and production of cutin with suberin-like monomers.

PubMed

Li, Yonghua; Beisson, Fred; Koo, Abraham J K; Molina, Isabel; Pollard, Mike; Ohlrogge, John

2007-11-13

Cutin and suberin are the two major lipid-based polymers of plants. Cutin is the structural polymer of the epidermal cuticle, the waterproof layer covering primary aerial organs and which is often the structure first encountered by phytopathogens. Suberin contributes to the control of diffusion of water and solutes across internal root tissues and in periderms. The enzymes responsible for assembly of the cutin polymer are largely unknown. We have identified two Arabidopsis acyltransferases essential for cutin biosynthesis, glycerol-3-phosphate acyltransferase (GPAT) 4 and GPAT8. Double knockouts gpat4/gpat8 were strongly reduced in cutin and were less resistant to desiccation and to infection by the fungus Alternaria brassicicola. They also showed striking defects in stomata structure including a lack of cuticular ledges between guard cells, highlighting the importance of cutin in stomatal biology. Overexpression of GPAT4 or GPAT8 in Arabidopsis increased the content of C16 and C18 cutin monomers in leaves and stems by 80%. In order to modify cutin composition, the acyltransferase GPAT5 and the cytochrome P450-dependent fatty acyl oxidase CYP86A1, two enzymes associated with suberin biosynthesis, were overexpressed. When both enzymes were overexpressed together the epidermal polyesters accumulated new C20 and C22 omega-hydroxyacids and alpha,omega-diacids typical of suberin, and the fine structure and water-barrier function of the cuticle were altered. These results identify GPATs as partners of fatty acyl oxidases in lipid polyester synthesis and indicate that their cooverexpression provides a strategy to probe the role of cutin composition and quantity in the function of plant cuticles.

Identification of acyltransferases required for cutin biosynthesis and production of cutin with suberin-like monomers

PubMed Central

Li, Yonghua; Beisson, Fred; Koo, Abraham J. K.; Molina, Isabel; Pollard, Mike; Ohlrogge, John

2007-01-01

Cutin and suberin are the two major lipid-based polymers of plants. Cutin is the structural polymer of the epidermal cuticle, the waterproof layer covering primary aerial organs and which is often the structure first encountered by phytopathogens. Suberin contributes to the control of diffusion of water and solutes across internal root tissues and in periderms. The enzymes responsible for assembly of the cutin polymer are largely unknown. We have identified two Arabidopsis acyltransferases essential for cutin biosynthesis, glycerol-3-phosphate acyltransferase (GPAT) 4 and GPAT8. Double knockouts gpat4/gpat8 were strongly reduced in cutin and were less resistant to desiccation and to infection by the fungus Alternaria brassicicola. They also showed striking defects in stomata structure including a lack of cuticular ledges between guard cells, highlighting the importance of cutin in stomatal biology. Overexpression of GPAT4 or GPAT8 in Arabidopsis increased the content of C16 and C18 cutin monomers in leaves and stems by 80%. In order to modify cutin composition, the acyltransferase GPAT5 and the cytochrome P450-dependent fatty acyl oxidase CYP86A1, two enzymes associated with suberin biosynthesis, were overexpressed. When both enzymes were overexpressed together the epidermal polyesters accumulated new C20 and C22 ω-hydroxyacids and α,ω-diacids typical of suberin, and the fine structure and water-barrier function of the cuticle were altered. These results identify GPATs as partners of fatty acyl oxidases in lipid polyester synthesis and indicate that their cooverexpression provides a strategy to probe the role of cutin composition and quantity in the function of plant cuticles. PMID:17991776

The formation of 3 alpha- and 3 beta-acetoxytropanes by Datura stramonium transformed root cultures involves two acetyl-CoA-dependent acyltransferases.

PubMed

Robins, R J; Bachmann, P; Robinson, T; Rhodes, M J; Yamada, Y

1991-11-04

Tropine (tropan-3 alpha-ol) is an intermediate in the formation of hyoscyamine. An acyltransferase activity that can acetylate tropine using acetylcoenzyme A as cosubstrate has been found in transformed root cultures of Datura stramonium. A further acyltransferase activity that acetylates pseudotropine (tropan-3 beta-ol) with acetyl-coenzyme A is also present. These two activities can be partially resolved by anion-exchange chromatography, some fractions containing only the pseudotropine-utilizing activity. The basic properties of these two enzymes are reported and their roles in forming the observed alkaloid spectrum of D. stramonium roots discussed.

ATP-binding cassette transporters and sterol O-acyltransferases interact at membrane microdomains to modulate sterol uptake and esterification.

PubMed

Gulati, Sonia; Balderes, Dina; Kim, Christine; Guo, Zhongmin A; Wilcox, Lisa; Area-Gomez, Estela; Snider, Jamie; Wolinski, Heimo; Stagljar, Igor; Granato, Juliana T; Ruggles, Kelly V; DeGiorgis, Joseph A; Kohlwein, Sepp D; Schon, Eric A; Sturley, Stephen L

2015-11-01

A key component of eukaryotic lipid homeostasis is the esterification of sterols with fatty acids by sterol O-acyltransferases (SOATs). The esterification reactions are allosterically activated by their sterol substrates, the majority of which accumulate at the plasma membrane. We demonstrate that in yeast, sterol transport from the plasma membrane to the site of esterification is associated with the physical interaction of the major SOAT, acyl-coenzyme A:cholesterol acyltransferase (ACAT)-related enzyme (Are)2p, with 2 plasma membrane ATP-binding cassette (ABC) transporters: Aus1p and Pdr11p. Are2p, Aus1p, and Pdr11p, unlike the minor acyltransferase, Are1p, colocalize to sterol and sphingolipid-enriched, detergent-resistant microdomains (DRMs). Deletion of either ABC transporter results in Are2p relocalization to detergent-soluble membrane domains and a significant decrease (53-36%) in esterification of exogenous sterol. Similarly, in murine tissues, the SOAT1/Acat1 enzyme and activity localize to DRMs. This subcellular localization is diminished upon deletion of murine ABC transporters, such as Abcg1, which itself is DRM associated. We propose that the close proximity of sterol esterification and transport proteins to each other combined with their residence in lipid-enriched membrane microdomains facilitates rapid, high-capacity sterol transport and esterification, obviating any requirement for soluble intermediary proteins. © FASEB.

Novel serum biomarkers for detection of excessive alcohol use

PubMed Central

Liangpunsakul, Suthat; Lai, Xianyin; Ross, Ruth A.; Yu, Zhangsheng; Modlik, Elizabeth; Westerhold, Chi; Heathers, Laura; Paul, Robin; O’Connor, Sean; Crabb, David W.; Witzmann, Frank

2015-01-01

Objectives Construct interview that correctly identifies those with alcohol use disorder have limitation, especially when the subjects are motivated to minimize the magnitude of drinking behavior. Current laboratory tests to detect excessive alcohol consumption are limited by marginal sensitivity/specificity. Excessive drinking has been shown to affect several organ systems; which may be reflected in changes in quantity of plasma proteins. Our aim was to employ novel proteomic analyses to identify potential markers for excessive alcohol use. METHODS A prospective case-control study that included 39 controls and 54 excessive drinkers (discovery cohort). The serum proteomic analyses in these subjects were performed and the results were tested in the verification cohort (40 controls and 40 excessive drinkers). RESULTS Using the appropriate cutoff and confirmation with ELISA, we identified 4 proteins which were significantly elevated in the serum of excessive drinkers; AT-rich interactive domain-containing protein 4B (ARID4B), Phosphatidylcholine-sterol acyltransferase (LCAT), Hepatocyte growth factor-like protein (MST1), and ADP-ribosylation factor 6 (ARL6). The performance of the conventional markers (AST, ALT, GGT, %CDT, and MCV) discriminating between excessive alcohol use and controls had an area under the curve (AUC) ranging from 0.21 (ALT) to 0.67 (MCV). The AUC of these novel proteins showed the improvement in the detection of excessive drinkers compared to conventional lab tests, ranging from 0.73 (for ARID4B) to 0.86 (for ARL6). CONCLUSIONS We have identified four novel proteins that can discern subjects with excessive alcohol use. Further studies are needed to determine the clinical implications of these markers to detect excessive alcohol use and confirm abstinence. PMID:25704570

Castor diacylglycerol acyltransferase type1(DGAT1)displays greater activity with diricinolein than Arabidopsis DGAT1

USDA-ARS?s Scientific Manuscript database

Castor oil contains the hydroxy fatty acid ricinoleate as a major (90%) component. The diacylglycerol acyltransferase (DGAT) carries out the final reaction step in the biosynthesis of triacylglycerol, the principal constituent of seed oil, and has been considered to be the step that controls the oil...

Defining the extreme substrate specificity of Euonymus alatus diacylglycerol acetyltransferase, an unusual membrane-bound O-acyltransferase

DOE PAGES

Bansal, Sunil; Durrett, Timothy P.

2016-11-08

Euonymus alatus diacylglycerol acetyltransferase (EaDAcT) synthesizes the unusually structured 3-acetyl-1,2-diacylglycerols (acetyl-TAG) found in the seeds of a few plant species. A member of the membrane-bound O-acyltransferase (MBOAT) family, EaDAcT transfers the acetyl group from acetyl-CoA to sn-1,2-diacylglycerol (DAG) to produce acetyl-TAG. In vitro assays demonstrated that the enzyme is also able to utilize butyryl-CoA and hexanoyl-CoA as acyl donors, though with much less efficiency compared with acetyl-CoA. Acyl-CoAs longer than eight carbons were not used by EaDAcT. This extreme substrate specificity of EaDAcT distinguishes it from all other MBOATs which typically catalyze the transfer of much longer acyl groups. Inmore » vitro selectivity experiments revealed that EaDAcT preferentially acetylated DAG molecules containing more double bonds over those with less. However, the enzyme was also able to acetylate saturated DAG containing medium chain fatty acids, albeit with less efficiency. Interestingly, EaDAcT could only acetylate the free hydroxyl group of sn-1,2-DAG but not the available hydroxyl groups in sn-1,3-DAG or in monoacylglycerols (MAG). Consistent with its similarity to the jojoba wax synthase, EaDAcT could acetylate fatty alcohols in vitro to produce alkyl acetates. Likewise, when coexpressed in yeast with a fatty acyl-CoA reductase capable of producing fatty alcohols, EaDAcT synthesized alkyl acetates although the efficiency of production was low. As a result, this improved understanding of EaDAcT specificity confirms that the enzyme preferentially utilizes acetyl-CoA to acetylate sn-1,2-DAGs and will be helpful in engineering the production of acetyl-TAG with improved functionality in transgenic plants.« less

Defining the extreme substrate specificity of Euonymus alatus diacylglycerol acetyltransferase, an unusual membrane-bound O-acyltransferase

PubMed Central

Bansal, Sunil; Durrett, Timothy P.

2016-01-01

Euonymus alatus diacylglycerol acetyltransferase (EaDAcT) synthesizes the unusually structured 3-acetyl-1,2-diacylglycerols (acetyl-TAG) found in the seeds of a few plant species. A member of the membrane-bound O-acyltransferase (MBOAT) family, EaDAcT transfers the acetyl group from acetyl-CoA to sn-1,2-diacylglycerol (DAG) to produce acetyl-TAG. In vitro assays demonstrated that the enzyme is also able to utilize butyryl-CoA and hexanoyl-CoA as acyl donors, though with much less efficiency compared with acetyl-CoA. Acyl-CoAs longer than eight carbons were not used by EaDAcT. This extreme substrate specificity of EaDAcT distinguishes it from all other MBOATs which typically catalyze the transfer of much longer acyl groups. In vitro selectivity experiments revealed that EaDAcT preferentially acetylated DAG molecules containing more double bonds over those with less. However, the enzyme was also able to acetylate saturated DAG containing medium chain fatty acids, albeit with less efficiency. Interestingly, EaDAcT could only acetylate the free hydroxyl group of sn-1,2-DAG but not the available hydroxyl groups in sn-1,3-DAG or in monoacylglycerols (MAG). Consistent with its similarity to the jojoba wax synthase, EaDAcT could acetylate fatty alcohols in vitro to produce alkyl acetates. Likewise, when coexpressed in yeast with a fatty acyl-CoA reductase capable of producing fatty alcohols, EaDAcT synthesized alkyl acetates although the efficiency of production was low. This improved understanding of EaDAcT specificity confirms that the enzyme preferentially utilizes acetyl-CoA to acetylate sn-1,2-DAGs and will be helpful in engineering the production of acetyl-TAG with improved functionality in transgenic plants. PMID:27688773

Defining the extreme substrate specificity of Euonymus alatus diacylglycerol acetyltransferase, an unusual membrane-bound O-acyltransferase

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bansal, Sunil; Durrett, Timothy P.

Euonymus alatus diacylglycerol acetyltransferase (EaDAcT) synthesizes the unusually structured 3-acetyl-1,2-diacylglycerols (acetyl-TAG) found in the seeds of a few plant species. A member of the membrane-bound O-acyltransferase (MBOAT) family, EaDAcT transfers the acetyl group from acetyl-CoA to sn-1,2-diacylglycerol (DAG) to produce acetyl-TAG. In vitro assays demonstrated that the enzyme is also able to utilize butyryl-CoA and hexanoyl-CoA as acyl donors, though with much less efficiency compared with acetyl-CoA. Acyl-CoAs longer than eight carbons were not used by EaDAcT. This extreme substrate specificity of EaDAcT distinguishes it from all other MBOATs which typically catalyze the transfer of much longer acyl groups. Inmore » vitro selectivity experiments revealed that EaDAcT preferentially acetylated DAG molecules containing more double bonds over those with less. However, the enzyme was also able to acetylate saturated DAG containing medium chain fatty acids, albeit with less efficiency. Interestingly, EaDAcT could only acetylate the free hydroxyl group of sn-1,2-DAG but not the available hydroxyl groups in sn-1,3-DAG or in monoacylglycerols (MAG). Consistent with its similarity to the jojoba wax synthase, EaDAcT could acetylate fatty alcohols in vitro to produce alkyl acetates. Likewise, when coexpressed in yeast with a fatty acyl-CoA reductase capable of producing fatty alcohols, EaDAcT synthesized alkyl acetates although the efficiency of production was low. As a result, this improved understanding of EaDAcT specificity confirms that the enzyme preferentially utilizes acetyl-CoA to acetylate sn-1,2-DAGs and will be helpful in engineering the production of acetyl-TAG with improved functionality in transgenic plants.« less

Characterization of acyl-coenzyme A:diacylglycerol acyltransferase (DGAT) enzyme of human small intestine.

PubMed

Hiramine, Yasushi; Tanabe, Toshizumi

2011-06-01

Acyl-coenzyme A:diacylglycerol acyltransferase (DGAT) enzyme plays a significant role in dietary triacylglycerol (TAG) absorption in the small intestine. However, the characteristics of human intestinal DGAT enzyme have not been examined in detail. The aim of our study was to characterize the human intestinal DGAT enzyme by examining acyl-CoA specificity, temperature dependency, and selectivity for 1,2-diacylglycerol (DAG) or 1,3-DAG. We detected DGAT activity of human intestinal microsome and found that the acyl-CoA specificity and temperature dependency of intestinal DGAT coincided with those of recombinant human DGAT1. To elucidate the selectivity of human intestinal DGAT to 1,2-DAG or 1,3-DAG, we conducted acyl-coenzyme A:monoacylglycerol acyltransferase assays using 1- or 2-monoacylglycerol (MAG) as substrates. When 2-MAG was used as acyl acceptor, both 1,2-DAG and TAG were generated; however, when 1-MAG was used, 1,3-DAG was predominantly observed and little TAG was detected. These findings suggest that human small intestinal DGAT, which is mainly encoded by DGAT1, utilizes 1,2-DAG as the substrate to form TAG. This study will contribute to understand the lipid absorption profile in the small intestine.

Evaluation of sterol transport from the endoplasmic reticulum to mitochondria using mitochondrially targeted bacterial sterol acyltransferase in Saccharomyces cerevisiae.

PubMed

Tian, Siqi; Ohta, Akinori; Horiuchi, Hiroyuki; Fukuda, Ryouichi

2015-01-01

To elucidate the mechanism of interorganelle sterol transport, a system to evaluate sterol transport from the endoplasmic reticulum (ER) to the mitochondria was constructed. A bacterial glycerophospholipid: cholesterol acyltransferase fused with a mitochondria-targeting sequence and a membrane-spanning domain of the mitochondrial inner membrane protein Pet100 and enhanced green fluorescent protein was expressed in a Saccharomyces cerevisiae mutant deleted for ARE1 and ARE2 encoding acyl-CoA:sterol acyltransferases. Microscopic observation and subcellular fractionation suggested that this fusion protein, which was named mito-SatA-EGFP, was localized in the mitochondria. Steryl esters were synthesized in the mutant expressing mito-SatA-EGFP. This system will be applicable for evaluations of sterol transport from the ER to the mitochondria in yeast by examining sterol esterification in the mitochondria.

A soluble diacylglycerol acyltransferase is involved in triacylglycerol biosynthesis in the oleaginous yeast Rhodotorula glutinis.

PubMed

Rani, Sapa Hima; Saha, Saikat; Rajasekharan, Ram

2013-01-01

The biosynthesis of triacylglycerol (TAG) occurs in the microsomal membranes of eukaryotes. Here, we report the identification and functional characterization of diacylglycerol acyltransferase (DGAT), a member of the 10 S cytosolic TAG biosynthetic complex (TBC) in Rhodotorula glutinis. Both a full-length and an N-terminally truncated cDNA clone of a single gene were isolated from R. glutinis. The DGAT activity of the protein encoded by RgDGAT was confirmed in vivo by the heterologous expression of cDNA in a Saccharomyces cerevisiae quadruple mutant (H1246) that is defective in TAG synthesis. RgDGAT overexpression in yeast was found to be capable of acylating diacylglycerol (DAG) in an acyl-CoA-dependent manner. Quadruple mutant yeast cells exhibit growth defects in the presence of oleic acid, but wild-type yeast cells do not. In an in vivo fatty acid supplementation experiment, RgDGAT expression rescued quadruple mutant growth in an oleate-containing medium. We describe a soluble acyl-CoA-dependent DAG acyltransferase from R. glutinis that belongs to the DGAT3 class of enzymes. The study highlights the importance of an alternative TAG biosynthetic pathway in oleaginous yeasts.

Mutants of Escherichia coli defective in membrane phospholipid synthesis: macromolecular synthesis in an sn-glycerol 3-phosphate acyltransferase Km mutant.

PubMed

Bell, R M

1974-03-01

sn-Glycerol 3-phosphate (G3P) auxotrophs of Escherichia coli have been selected from a strain which cannot aerobically catabolize G3P. The auxotrophy resulted from loss of the biosynthetic G3P dehydrogenase (EC 1.1.1.8) or from a defective membranous G3P acyltransferase. The apparent K(m) of the acyltransferase for G3P was 11- to 14-fold higher (from about 90 mum to 1,000 to 1,250 mum) in membrane preparations from the mutants than those of the parent. All extracts prepared from revertants of the G3P dehydrogenase mutants showed G3P dehydrogenase activity, but most contained less than 10% of the wild-type level. Membrane preparations from revertants of the acyltransferase mutants had apparent K(m)'s for G3P similar to that of the parent. Strains have been derived in which the G3P requirement can be satisfied with glycerol in the presence of glucose, presumably because the glycerol kinase was desensitized to inhibition by fructose 1,6-diphosphate. Investigations on the growth and macromolecular synthesis in a G3P acyltransferase K(m) mutant revealed that upon glycerol deprivation, net phospholipid synthesis stopped immediately; growth continued for about one doubling; net ribonucleic acid (RNA), deoxyribonucleic acid (DNA), and protein nearly doubled paralleling the growth curve; the rate of phospholipid synthesis assessed by labeling cells with (32)P-phosphate, (14)C-acetate, or (3)H-serine was reduced greater than 90%; the rates of RNA and DNA synthesis increased as the cells grew and then decreased as the cells stopped growing; the rate of protein synthesis showed no increase and declined more slowly than the rates of RNA and DNA synthesis when the cells stopped growing. The cells retained and gained in the capacity to synthesize phospholipids upon glycerol deprivation. These data indicate that net phospholipid synthesis is not required for continued macromolecular synthesis for about one doubling, and that the rates of these processes are not coupled during this

Acyl-CoA:Lysophosphatidylethanolamine Acyltransferase Activity Regulates Growth of Arabidopsis1

PubMed Central

Jasieniecka-Gazarkiewicz, Katarzyna; Lager, Ida; Carlsson, Anders S.; Gutbrod, Katharina; Peisker, Helga; Dörmann, Peter; Stymne, Sten; Banaś, Antoni

2017-01-01

Arabidopsis (Arabidopsis thaliana) contains two enzymes (encoded by the At1g80950 and At2g45670 genes) preferentially acylating lysophosphatidylethanolamine (LPE) with acyl-coenzyme A (CoA), designated LYSOPHOSPHATIDYLETHANOLAMINE ACYLTRANSFERASE1 (LPEAT1) and LPEAT2. The transfer DNA insertion mutant lpeat2 and the double mutant lpeat1 lpeat2 showed impaired growth, smaller leaves, shorter roots, less seed setting, and reduced lipid content per fresh weight in roots and seeds and large increases in LPE and lysophosphatidylcholine (LPC) contents in leaves. Microsomal preparations from leaves of these mutants showed around 70% decrease in acylation activity of LPE with 16:0-CoA compared with wild-type membranes, whereas the acylation with 18:1-CoA was much less affected, demonstrating that other lysophospholipid acyltransferases than the two LPEATs could acylate LPE. The above-mentioned effects were less pronounced in the single lpeat1 mutant. Overexpression of either LPEAT1 or LPEAT2 under the control of the 35S promotor led to morphological changes opposite to what was seen in the transfer DNA mutants. Acyl specificity studies showed that LPEAT1 utilized 16:0-CoA at the highest rate of 11 tested acyl-CoAs, whereas LPEAT2 utilized 20:0-CoA as the best acyl donor. Both LPEATs could acylate either sn position of ether analogs of LPC. The data show that the activities of LPEAT1 and LPEAT2 are, in a complementary way, involved in growth regulation in Arabidopsis. It is shown that LPEAT activity (especially LPEAT2) is essential for maintaining adequate levels of phosphatidylethanolamine, LPE, and LPC in the cells. PMID:28408542

Studies on the substrate and stereo/regioselectivity of adipose triglyceride lipase, hormone-sensitive lipase, and diacylglycerol-O-acyltransferases.

PubMed

Eichmann, Thomas O; Kumari, Manju; Haas, Joel T; Farese, Robert V; Zimmermann, Robert; Lass, Achim; Zechner, Rudolf

2012-11-30

Adipose triglyceride lipase (ATGL) is rate-limiting for the initial step of triacylglycerol (TAG) hydrolysis, generating diacylglycerol (DAG) and fatty acids. DAG exists in three stereochemical isoforms. Here we show that ATGL exhibits a strong preference for the hydrolysis of long-chain fatty acid esters at the sn-2 position of the glycerol backbone. The selectivity of ATGL broadens to the sn-1 position upon stimulation of the enzyme by its co-activator CGI-58. sn-1,3 DAG is the preferred substrate for the consecutive hydrolysis by hormone-sensitive lipase. Interestingly, diacylglycerol-O-acyltransferase 2, present at the endoplasmic reticulum and on lipid droplets, preferentially esterifies sn-1,3 DAG. This suggests that ATGL and diacylglycerol-O-acyltransferase 2 act coordinately in the hydrolysis/re-esterification cycle of TAGs on lipid droplets. Because ATGL preferentially generates sn-1,3 and sn-2,3, it suggests that TAG-derived DAG cannot directly enter phospholipid synthesis or activate protein kinase C without prior isomerization.

A Specialized Diacylglycerol Acyltransferase Contributes to the Extreme Medium-Chain Fatty Acid Content of Cuphea Seed Oil.

PubMed

Iskandarov, Umidjon; Silva, Jillian E; Kim, Hae Jin; Andersson, Mariette; Cahoon, Rebecca E; Mockaitis, Keithanne; Cahoon, Edgar B

2017-05-01

Seed oils of many Cuphea sp. contain >90% of medium-chain fatty acids, such as decanoic acid (10:0). These seed oils, which are among the most compositionally variant in the plant kingdom, arise from specialized fatty acid biosynthetic enzymes and specialized acyltransferases. These include lysophosphatidic acid acyltransferases (LPAT) and diacylglycerol acyltransferases (DGAT) that are required for successive acylation of medium-chain fatty acids in the sn -2 and sn -3 positions of seed triacylglycerols (TAGs). Here we report the identification of a cDNA for a DGAT1-type enzyme, designated CpuDGAT1, from the transcriptome of C. avigera var pulcherrima developing seeds. Microsomes of camelina ( Camelina sativa ) seeds engineered for CpuDGAT1 expression displayed DGAT activity with 10:0-CoA and the diacylglycerol didecanoyl, that was approximately 4-fold higher than that in camelina seed microsomes lacking CpuDGAT1. In addition, coexpression in camelina seeds of CpuDGAT1 with a C. viscosissima FatB thioesterase (CvFatB1) that generates 10:0 resulted in TAGs with nearly 15 mol % of 10:0. More strikingly, expression of CpuDGAT1 and CvFatB1 with the previously described CvLPAT2, a 10:0-CoA-specific Cuphea LPAT, increased 10:0 amounts to 25 mol % in camelina seed TAG. These TAGs contained up to 40 mol % 10:0 in the sn -2 position, nearly double the amounts obtained from coexpression of CvFatB1 and CvLPAT2 alone. Although enriched in diacylglycerol, 10:0 was not detected in phosphatidylcholine in these seeds. These findings are consistent with channeling of 10:0 into TAG through the combined activities of specialized LPAT and DGAT activities and demonstrate the biotechnological use of these enzymes to generate 10:0-rich seed oils. © 2017 American Society of Plant Biologists. All Rights Reserved.

Adult Students' Perceptions of Automated Writing Assessment Software: Does It Foster Engagement?

ERIC Educational Resources Information Center

LaGuerre, Joselle L.

2013-01-01

Generally, this descriptive study endeavored to include the voice of adult learners to the scholarly body of research regarding automated writing assessment tools (AWATs). Specifically, the study sought to determine the extent to which students perceive that the AWAT named Criterion fosters learning and if students' opinions differ depending on…

Novel LC/MS/MS and High-Throughput Mass Spectrometric Assays for Monoacylglycerol Acyltransferase Inhibitors.

PubMed

Qi, Jenson; Masucci, John A; Lang, Wensheng; Connelly, Margery A; Caldwell, Gary W; Petrounia, Ioanna; Kirkpatrick, Jennifer; Barnakov, Alexander N; Struble, Geoffrey; Miller, Robyn; Dzordzorine, Keli; Kuo, Gee-Hong; Gaul, Michael; Pocai, Alessandro; Lee, Seunghun

2017-04-01

Monoacylglycerol acyltransferase enzymes (MGAT1, MGAT2, and MGAT3) convert monoacylglycerol to diacylglycerol (DAG). MGAT1 and MGAT2 are both implicated in obesity-related metabolic diseases. Conventional MGAT enzyme assays use radioactive substrates, wherein the product of the MGAT-catalyzed reaction is usually resolved by time-consuming thin layer chromatography (TLC) analysis. Furthermore, microsomal membrane preparations typically contain endogenous diacylglycerol acyltransferase (DGAT) from the host cells, and these DGAT activities can further acylate DAG to form triglyceride (TG). Our mass spectrometry (liquid chromatography-tandem mass spectrometry, or LC/MS/MS) MGAT2 assay measures human recombinant MGAT2-catalyzed formation of didecanoyl-glycerol from 1-decanoyl-rac-glycerol and decanoyl-CoA, to produce predominantly 1,3-didecanoyl-glycerol. Unlike 1,2-DAG, 1,3-didecanoyl-glycerol is proved to be not susceptible to further acylation to TG. 1,3-Didecanoyl-glycerol product can be readily solubilized and directly subjected to high-throughput mass spectrometry (HTMS) without further extraction in a 384-well format. We also have established the LC/MS/MS MGAT activity assay in the intestinal microsomes from various species. Our assay is proved to be highly sensitive, and thus it allows measurement of endogenous MGAT activity in cell lysates and tissue preparations. The implementation of the HTMS MGAT activity assay has facilitated the robust screening and evaluation of MGAT inhibitors for the treatment of metabolic diseases.

Two bifunctional enzymes from the marine protist Thraustochytrium roseum: biochemical characterization of wax ester synthase/acyl-CoA:diacylglycerol acyltransferase activity catalyzing wax ester and triacylglycerol synthesis.

PubMed

Zhang, Nannan; Mao, Zejing; Luo, Ling; Wan, Xia; Huang, Fenghong; Gong, Yangmin

2017-01-01

Triacylglycerols (TAGs) and wax esters (WEs) are important neutral lipids which serve as energy reservoir in some plants and microorganisms. In recent years, these biologically produced neutral lipids have been regarded as potential alternative energy sources for biofuel production because of the increased interest on developing renewable and environmentally benign alternatives for fossil fuels. In bacteria, the final step in TAG and WE biosynthetic pathway is catalyzed by wax ester synthase/acyl coenzyme A (acyl-CoA):diacylglycerol acyltransferase (WS/DGAT). This bifunctional WS/DGAT enzyme is also a key enzyme in biotechnological production of liquid WE via engineering of plants and microorganisms. To date, knowledge about this class of biologically and biotechnologically important enzymes is mainly from biochemical characterization of WS/DGATs from Arabidopsis, jojoba and some bacteria that can synthesize both TAGs and WEs intracellularly, whereas little is known about WS/DGATs from eukaryotic microorganisms. Here, we report the identification and characterization of two bifunctional WS/DGAT enzymes (designated TrWSD4 and TrWSD5) from the marine protist Thraustochytrium roseum . Both TrWSD4 and TrWSD5 comprise a WS-like acyl-CoA acyltransferase domain and the recombinant proteins purified from Escherichia coli Rosetta (DE3) have substantial WS and lower DGAT activity. They exhibit WS activity towards various-chain-length saturated and polyunsaturated acyl-CoAs and fatty alcohols ranging from C 10 to C 18 . TrWSD4 displays WS activity with the lowest K m value of 0.14 μM and the highest k cat / K m value of 1.46 × 10 5  M -1  s -1 for lauroyl-CoA (C 12:0 ) in the presence of 100 μM hexadecanol, while TrWSD5 exhibits WS activity with the lowest K m value of 0.96 μM and the highest k cat / K m value of 9.83 × 10 4  M -1  s -1 for decanoyl-CoA (C 10:0 ) under the same reaction condition. Both WS/DGAT enzymes have the highest WS activity at 37 and 47�

The Great Roundleaf Bat (Hipposideros armiger) as a Good Model for Cold-Induced Browning of Intra-Abdominal White Adipose Tissue

PubMed Central

Ke, Shanshan; Fang, Na; Irwin, David M.; Lei, Ming; Zhang, Junpeng; Shi, Huizhen; Zhang, Shuyi; Wang, Zhe

2014-01-01

Background Inducing beige fat from white adipose tissue (WAT) is considered to be a shortcut to weight loss and increasingly becoming a key area in research into treatments for obesity and related diseases. However, currently, animal models of beige fat are restricted to rodents, where subcutaneous adipose tissue (sWAT, benign WAT) is more liable to develop into the beige fat under specific activators than the intra-abdominal adipose tissue (aWAT, malignant WAT) that is the major source of obesity related diseases in humans. Methods Here we induced beige fat by cold exposure in two species of bats, the great roundleaf bat (Hipposideros armiger) and the rickett's big-footed bat (Myotis ricketti), and compared the molecular and morphological changes with those seen in the mouse. Expression of thermogenic genes (Ucp1 and Pgc1a) was measured by RT-qPCR and adipocyte morphology examined by HE staining at three adipose locations, sWAT, aWAT and iBAT (interscapular brown adipose tissue). Results Expression of Ucp1 and Pgc1a was significantly upregulated, by 729 and 23 fold, respectively, in aWAT of the great roundleaf bat after exposure to 10°C for 7 days. Adipocyte diameters of WATs became significantly reduced and the white adipocytes became brown-like in morphology. In mice, similar changes were found in the sWAT, but much lower amounts of changes in aWAT were seen. Interestingly, the rickett's big-footed bat did not show such a tendency in beige fat. Conclusions The great roundleaf bat is potentially a good animal model for human aWAT browning research. Combined with rodent models, this model should be helpful for finding therapies for reducing harmful aWAT in humans. PMID:25393240

Discovery of a novel series of benzimidazole derivatives as diacylglycerol acyltransferase inhibitors.

PubMed

Lee, Kyeong; Goo, Ja-Il; Jung, Hwa Young; Kim, Minkyoung; Boovanahalli, Shanthaveerappa K; Park, Hye Ran; Kim, Mun-Ock; Kim, Dong-Hyun; Lee, Hyun Sun; Choi, Yongseok

2012-12-15

A novel series of benzimidazole derivatives was prepared and evaluated for their diacylglycerol acyltransferase (DGAT) inhibitory activity using microsome from rat liver. Among the newly synthesized compounds, furfurylamine containing benzimidazole carboxamide 10j showed the most potent DGAT inhibitory effect (IC(50)=4.4 μM) and inhibited triglyceride formation in HepG2 cells. Furthermore, compound 10j reduced body weight gain of Institute of Cancer Research mice on a high-fat diet and decreased levels of total triglyceride, total cholesterol, and LDL-cholesterol in the blood accompanied with a significant increase in HDL-cholesterol level. Copyright © 2012 Elsevier Ltd. All rights reserved.

Discovery and Optimization of Imidazopyridine-Based Inhibitors of Diacylglycerol Acyltransferase 2 (DGAT2).

PubMed

Futatsugi, Kentaro; Kung, Daniel W; Orr, Suvi T M; Cabral, Shawn; Hepworth, David; Aspnes, Gary; Bader, Scott; Bian, Jianwei; Boehm, Markus; Carpino, Philip A; Coffey, Steven B; Dowling, Matthew S; Herr, Michael; Jiao, Wenhua; Lavergne, Sophie Y; Li, Qifang; Clark, Ronald W; Erion, Derek M; Kou, Kou; Lee, Kyuha; Pabst, Brandon A; Perez, Sylvie M; Purkal, Julie; Jorgensen, Csilla C; Goosen, Theunis C; Gosset, James R; Niosi, Mark; Pettersen, John C; Pfefferkorn, Jeffrey A; Ahn, Kay; Goodwin, Bryan

2015-09-24

The medicinal chemistry and preclinical biology of imidazopyridine-based inhibitors of diacylglycerol acyltransferase 2 (DGAT2) is described. A screening hit 1 with low lipophilic efficiency (LipE) was optimized through two key structural modifications: (1) identification of the pyrrolidine amide group for a significant LipE improvement, and (2) insertion of a sp(3)-hybridized carbon center in the core of the molecule for simultaneous improvement of N-glucuronidation metabolic liability and off-target pharmacology. The preclinical candidate 9 (PF-06424439) demonstrated excellent ADMET properties and decreased circulating and hepatic lipids when orally administered to dyslipidemic rodent models.

Cholinephosphotransferase and Diacylglycerol Acyltransferase (Substrate Specificities at a Key Branch Point in Seed Lipid Metabolism).

PubMed

Vogel, G.; Browse, J.

1996-03-01

Many oilseed plants accumulate triacylglycerols that contain unusual fatty acyl structures rather than the common 16- and 18-carbon fatty acids found in membrane lipids of these plants. In vitro experiments demonstrate that triacylglycerols are synthesized via diacylglycerols in microsomal preparations and that this same sub-cellular fraction is the site for the synthesis of phosphatidylcholine, which in seeds is synthesized from diacylglycerol by CDP-choline: diacylglycerol cholinephosphotransferase. In microsomes from Cuphea lanceolata, a plant that accumulates fatty acids with 10 carbons and no double bonds (10:0) in its oil, the diacylglycerol acyltransferase exhibited 4-fold higher activity with 10:0/10:0 molecular species of diacylglycerol than with molecular species containing 18-carbon fatty acids. In castor bean (Ricinus communis), which accumulates oil containing ricinoleic acid, diricinoleoyldiacylglycerol was the favored substrate for triacylglycerol synthesis. In contrast to these modest specificities of the diacylglycerol acyltransferases, the cholinephosphotransferases from these plants and from safflower (Carthamus tinctorius) and rapeseed (Brassica napus) showed little or no specificity across a range of different diacylglycerol substrates. Consideration of these results and other data suggests that the targeting of unusual fatty acids to triacylglycerol synthesis and their exclusion from membrane lipids are not achieved on the basis of the diacylglycerol substrate specificities of the enzymes involved and may instead require the spatial separation of two different diacylglycerol pools.

Cholinephosphotransferase and Diacylglycerol Acyltransferase (Substrate Specificities at a Key Branch Point in Seed Lipid Metabolism).

PubMed Central

Vogel, G.; Browse, J.

1996-01-01

Many oilseed plants accumulate triacylglycerols that contain unusual fatty acyl structures rather than the common 16- and 18-carbon fatty acids found in membrane lipids of these plants. In vitro experiments demonstrate that triacylglycerols are synthesized via diacylglycerols in microsomal preparations and that this same sub-cellular fraction is the site for the synthesis of phosphatidylcholine, which in seeds is synthesized from diacylglycerol by CDP-choline: diacylglycerol cholinephosphotransferase. In microsomes from Cuphea lanceolata, a plant that accumulates fatty acids with 10 carbons and no double bonds (10:0) in its oil, the diacylglycerol acyltransferase exhibited 4-fold higher activity with 10:0/10:0 molecular species of diacylglycerol than with molecular species containing 18-carbon fatty acids. In castor bean (Ricinus communis), which accumulates oil containing ricinoleic acid, diricinoleoyldiacylglycerol was the favored substrate for triacylglycerol synthesis. In contrast to these modest specificities of the diacylglycerol acyltransferases, the cholinephosphotransferases from these plants and from safflower (Carthamus tinctorius) and rapeseed (Brassica napus) showed little or no specificity across a range of different diacylglycerol substrates. Consideration of these results and other data suggests that the targeting of unusual fatty acids to triacylglycerol synthesis and their exclusion from membrane lipids are not achieved on the basis of the diacylglycerol substrate specificities of the enzymes involved and may instead require the spatial separation of two different diacylglycerol pools. PMID:12226231

Monoacylglycerols are components of root waxes and can be produced in the aerial cuticle by ectopic expression of a suberin-associated acyltransferase.

PubMed

Li, Yonghua; Beisson, Fred; Ohlrogge, John; Pollard, Mike

2007-07-01

The interface between plants and the environment is provided for aerial organs by epicuticular waxes that have been extensively studied. By contrast, little is known about the nature, biosynthesis, and role of waxes at the root-rhizosphere interface. Waxes isolated by rapid immersion of Arabidopsis (Arabidopsis thaliana) roots in organic solvents were rich in saturated C18-C22 alkyl esters of p-hydroxycinnamic acids, but also contained significant amounts of both alpha- and beta-isomers of monoacylglycerols with C22 and C24 saturated acyl groups and the corresponding free fatty acids. Production of these compounds in root waxes was positively correlated to the expression of sn-glycerol-3-P acyltransferase5 (GPAT5), a gene encoding an acyltransferase previously shown to be involved in aliphatic suberin synthesis. This suggests a direct metabolic relationship between suberin and some root waxes. Furthermore, when ectopically expressed in Arabidopsis, GPAT5 produced very-long-chain saturated monoacylglycerols and free fatty acids as novel components of cuticular waxes. The crystal morphology of stem waxes was altered and the load of total stem wax compounds was doubled, although the major components typical of the waxes found on wild-type plants decreased. These results strongly suggest that GPAT5 functions in vivo as an acyltransferase to a glycerol-containing acceptor and has access to the same pool of acyl intermediates and/or may be targeted to the same membrane domain as that of wax synthesis in aerial organs.

A Specialized Diacylglycerol Acyltransferase Contributes to the Extreme Medium-Chain Fatty Acid Content of Cuphea Seed Oil1[OPEN

PubMed Central

Iskandarov, Umidjon; Silva, Jillian E.; Andersson, Mariette

2017-01-01

Seed oils of many Cuphea sp. contain >90% of medium-chain fatty acids, such as decanoic acid (10:0). These seed oils, which are among the most compositionally variant in the plant kingdom, arise from specialized fatty acid biosynthetic enzymes and specialized acyltransferases. These include lysophosphatidic acid acyltransferases (LPAT) and diacylglycerol acyltransferases (DGAT) that are required for successive acylation of medium-chain fatty acids in the sn-2 and sn-3 positions of seed triacylglycerols (TAGs). Here we report the identification of a cDNA for a DGAT1-type enzyme, designated CpuDGAT1, from the transcriptome of C. avigera var pulcherrima developing seeds. Microsomes of camelina (Camelina sativa) seeds engineered for CpuDGAT1 expression displayed DGAT activity with 10:0-CoA and the diacylglycerol didecanoyl, that was approximately 4-fold higher than that in camelina seed microsomes lacking CpuDGAT1. In addition, coexpression in camelina seeds of CpuDGAT1 with a C. viscosissima FatB thioesterase (CvFatB1) that generates 10:0 resulted in TAGs with nearly 15 mol % of 10:0. More strikingly, expression of CpuDGAT1 and CvFatB1 with the previously described CvLPAT2, a 10:0-CoA-specific Cuphea LPAT, increased 10:0 amounts to 25 mol % in camelina seed TAG. These TAGs contained up to 40 mol % 10:0 in the sn-2 position, nearly double the amounts obtained from coexpression of CvFatB1 and CvLPAT2 alone. Although enriched in diacylglycerol, 10:0 was not detected in phosphatidylcholine in these seeds. These findings are consistent with channeling of 10:0 into TAG through the combined activities of specialized LPAT and DGAT activities and demonstrate the biotechnological use of these enzymes to generate 10:0-rich seed oils. PMID:28325847

A Grapevine Anthocyanin Acyltransferase, Transcriptionally Regulated by VvMYBA, Can Produce Most Acylated Anthocyanins Present in Grape Skins1

PubMed Central

Rinaldo, Amy R.; Cavallini, Erika; Jia, Yong; Moss, Sarah M.A.; McDavid, Debra A.J.; Hooper, Lauren C.; Robinson, Simon P.; Tornielli, Giovanni B.; Zenoni, Sara; Ford, Christopher M.; Boss, Paul K.; Walker, Amanda R.

2015-01-01

Anthocyanins are flavonoid compounds responsible for red/purple colors in the leaves, fruit, and flowers of many plant species. They are produced through a multistep pathway that is controlled by MYB transcription factors. VvMYBA1 and VvMYBA2 activate anthocyanin biosynthesis in grapevine (Vitis vinifera) and are nonfunctional in white grapevine cultivars. In this study, transgenic grapevines with altered VvMYBA gene expression were developed, and transcript analysis was carried out on berries using a microarray technique. The results showed that VvMYBA is a positive regulator of the later stages of anthocyanin synthesis, modification, and transport in cv Shiraz. One up-regulated gene, ANTHOCYANIN 3-O-GLUCOSIDE-6″-O-ACYLTRANSFERASE (Vv3AT), encodes a BAHD acyltransferase protein (named after the first letter of the first four characterized proteins: BEAT [for acetyl CoA:benzylalcohol acetyltransferase], AHCT [for anthocyanin O-hydroxycinnamoyltransferase], HCBT [for anthranilate N-hydroxycinnamoyl/benzoyltransferase], and DAT [for deacetylvindoline 4-O-acetyltransferase]), belonging to a clade separate from most anthocyanin acyltransferases. Functional studies (in planta and in vitro) show that Vv3AT has a broad anthocyanin substrate specificity and can also utilize both aliphatic and aromatic acyl donors, a novel activity for this enzyme family found in nature. In cv Pinot Noir, a red-berried grapevine mutant lacking acylated anthocyanins, Vv3AT contains a nonsense mutation encoding a truncated protein that lacks two motifs required for BAHD protein activity. Promoter activation assays confirm that Vv3AT transcription is activated by VvMYBA1, which adds to the current understanding of the regulation of the BAHD gene family. The flexibility of Vv3AT to use both classes of acyl donors will be useful in the engineering of anthocyanins in planta or in vitro. PMID:26395841

Niemann-Pick C1-deficient mice lacking sterol O-acyltransferase 2 have less hepatic cholesterol entrapment and improved liver function.

PubMed

Lopez, Adam M; Jones, Ryan Dale; Repa, Joyce J; Turley, Stephen D

2018-06-07

Cholesteryl esters are generated at multiple sites in the body by sterol O-acyltransferase 1 (SOAT1) or sterol O-acyltransferase 2 (SOAT2) in various cell types, and lecithin cholesterol acyltransferase (LCAT) in plasma. Esterified cholesterol (EC) and triacylglycerol (TAG) contained in lipoproteins cleared from the circulation via receptor-mediated or bulk-phase endocytosis are hydrolyzed by lysosomal acid lipase (LAL) within the late endosomal/lysosomal (E/L) compartment. Then, through the successive actions of Niemann-Pick C2 (NPC2) and Niemann-Pick C1 (NPC1), unesterified cholesterol (UC) is exported from the E/L compartment to the cytosol. Mutations in either NPC1 or NPC2 lead to continuing entrapment of UC in all organs, resulting in multisystem disease which includes hepatic dysfunction and in some cases liver failure. These studies investigated primarily whether elimination of SOAT2 in NPC1-deficient mice impacted hepatic UC sequestration, inflammation, and transaminase activities. Measurements were made in 7 wk-old mice fed a low-cholesterol chow diet or one enriched with cholesterol starting 2 wk before study. In the chow-fed mice, NPC1:SOAT2 double knockouts, compared to their littermates lacking only NPC1, had 20% less liver mass, 28% lower hepatic UC concentrations, and plasma ALT and AST activities that were decreased by 48% and 36%, respectively. mRNA expression levels for several markers of inflammation were all significantly lower in the NPC1 mutants lacking SOAT2. The existence of a new class of potent and selective SOAT2 inhibitors provides an opportunity for exploring if suppression of this enzyme could potentially become an adjunctive therapy for liver disease in NPC1 deficiency.

Targeting palmitoyl acyltransferase ZDHHC21 improves gut epithelial barrier dysfunction resulting from burn-induced systemic inflammation.

PubMed

Haines, R J; Wang, C Y; Yang, C G Y; Eitnier, R A; Wang, F; Wu, M H

2017-12-01

Clinical studies in burn patients demonstrate a close association between leaky guts and increased incidence or severity of sepsis and other complications. Severe thermal injury triggers intestinal inflammation that contributes to intestinal epithelial hyperpermeability, which exacerbates systemic response leading to multiple organ failure and sepsis. In this study, we identified a significant function of a particular palmitoyl acyltransferase, zinc finger DHHC domain-containing protein-21 (ZDHHC21), in mediating signaling events required for gut hyperpermeability induced by inflammation. Using quantitative PCR, we show that ZDHHC21 mRNA production was enhanced twofold when intestinal epithelial cells were treated with TNF-α-IFN-γ in vitro. In addition, pharmacological targeting of palmitoyl acyltransferases with 2-bromopalmitate (2-BP) showed significant improvement in TNF-α-IFN-γ-mediated epithelial barrier dysfunction by using electric cell-substrate impedance-sensing assays, as well as FITC-labeled dextran permeability assays. Using acyl-biotin exchange assay and click chemistry, we show that TNF-α-IFN-γ treatment of intestinal epithelial cells results in enhanced detection of total palmitoylated proteins and this response is inhibited by 2-BP. Using ZDHHC21-deficient mice or wild-type mice treated with 2-BP, we showed that mice with impaired ZDHHC21 expression or pharmacological inhibition resulted in attenuated intestinal barrier dysfunction caused by thermal injury. Moreover, hematoxylin and eosin staining of the small intestine, as well as transmission electron microscopy, showed that mice with genetic interruption of ZDHHC21 had attenuated villus structure disorganization associated with thermal injury-induced intestinal barrier damage. Taken together, these results suggest an important role of ZDHHC21 in mediating gut hyperpermeability resulting from thermal injury. NEW & NOTEWORTHY Increased mucosal permeability in the gut is one of the major

Cloning and molecular characterization of a glycerol-3-phosphate O-acyltransferase (GPAT) gene from Echium (Boraginaceae) involved in the biosynthesis of cutin polyesters.

PubMed

Mañas-Fernández, Aurora; Li-Beisson, Yonghua; Alonso, Diego López; García-Maroto, Federico

2010-09-01

The glycerol-based lipid polyester called cutin is a main component of cuticle, the protective interface of aerial plant organs also controlling compound exchange with the environment. Though recent progress towards understanding of cutin biosynthesis has been made in Arabidopsis thaliana, little is known in other plants. One key step in this process is the acyl transfer reaction to the glycerol backbone. Here we report the cloning and molecular characterization of EpGPAT1, a gene encoding a glycerol-3-phosphate O-acyltransferase (GPAT) from Echium pitardii (Boraginaceae) with high similarity to the AtGPAT4/AtGPAT8 of Arabidopsis. Quantitative analysis by qRT-PCR showed highest expression of EpGPAT1 in seeds, roots, young leaves and flowers. Acyltransferase activity of EpGPAT1 was evidenced by heterologous expression in yeast. Ectopic expression in leaves of tobacco plants lead to an increase of C16 and C18 hydroxyacids and alpha,omega-diacids in the cell wall fraction, indicating a role in the biosynthesis of polyesters. Analysis of the genomic organization in Echium revealed the presence of EpGPAT2, a closely related gene which was found to be mostly expressed in developing leaves and flowers. The presence of a conserved HAD-like domain at the N-terminal moiety of GPATs from Echium, Arabidopsis and other plant species suggests a possible phosphohydrolase activity in addition to the reported acyltransferase activity. Evolutive implications of this finding are discussed.

High-Density Lipoprotein, Lecithin: Cholesterol Acyltransferase, and Atherosclerosis

PubMed Central

Ossoli, Alice; Pavanello, Chiara

2016-01-01

Epidemiological data clearly show the existence of a strong inverse correlation between plasma high-density lipoprotein cholesterol (HDL-C) concentrations and the incidence of coronary heart disease. This relation is explained by a number of atheroprotective properties of HDL, first of all the ability to promote macrophage cholesterol transport. HDL are highly heterogeneous and are continuously remodeled in plasma thanks to the action of a number of proteins and enzymes. Among them, lecithin:cholesterol acyltransferase (LCAT) plays a crucial role, being the only enzyme able to esterify cholesterol within lipoproteins. LCAT is synthetized by the liver and it has been thought to play a major role in reverse cholesterol transport and in atheroprotection. However, data from animal studies, as well as human studies, have shown contradictory results. Increased LCAT concentrations are associated with increased HDL-C levels but not necessarily with atheroprotection. On the other side, decreased LCAT concentration and activity are associated with decreased HDL-C levels but not with increased atherosclerosis. These contradictory results confirm that HDL-C levels per se do not represent the functionality of the HDL system. PMID:27302716

Lecithin:Cholesterol Acyltransferase Activation by Sulfhydryl-Reactive Small Molecules: Role of Cysteine-31

PubMed Central

Freeman, Lita A.; Demosky, Stephen J.; Konaklieva, Monika; Kuskovsky, Rostislav; Aponte, Angel; Ossoli, Alice F.; Gordon, Scott M.; Koby, Ross F.; Manthei, Kelly A.; Shen, Min; Vaisman, Boris L.; Shamburek, Robert D.; Jadhav, Ajit; Calabresi, Laura; Gucek, Marjan; Tesmer, John J.G.; Levine, Rodney L.

2017-01-01

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. Mass spectrometry and nuclear magnetic resonance were used to determine compound A adduct formation with LCAT. Molecular modeling was performed to gain insight into the effects of compound A on LCAT structure and activity. Compound A increased LCAT activity in a subset (three of nine) of LCAT mutations to levels comparable to FLD heterozygotes. The site-directed mutation LCAT-Cys31Gly prevented activation by compound A. Substitution of Cys31 with charged residues (Glu, Arg, and Lys) decreased LCAT activity, whereas bulky hydrophobic groups (Trp, Leu, Phe, and Met) increased activity up to 3-fold (P < 0.005). Mass spectrometry of a tryptic digestion of LCAT incubated with compound A revealed a +103.017 m/z adduct on Cys31, consistent with the addition of a single hydrophobic cyanopyrazine ring. Molecular modeling identified potential interactions of compound A near Cys31 and structural changes correlating with enhanced activity. Functional groups important for LCAT activation by compound A were identified by testing compound A derivatives. Finally, sulfhydryl-reactive β-lactams were developed as a new class of LCAT activators. In conclusion, compound A activates LCAT, including some FLD mutations, by forming a hydrophobic adduct with Cys31, thus providing a mechanistic rationale for the design of future LCAT activators. PMID:28576974

Trans unsaturated fatty acids inhibit lecithin: cholesterol acyltransferase and alter its positional specificity.

PubMed

Subbaiah, P V; Subramanian, V S; Liu, M

1998-07-01

Although dietary trans unsaturated fatty acids (TUFA) are known to decrease plasma HDL, the underlying mechanisms for this effect are unclear. We tested the hypothesis that the decreased HDL is due to an inhibition of lecithin:cholesterol acyltransferase (LCAT), the enzyme essential for the formation of HDL, by determining the activity of purified LCAT in the presence of synthetic phosphatidylcholine (PC) substrates containing TUFA. Both human and rat LCATs exhibited significantly lower activity (-37% to -50%) with PCs containing 18:1t or 18:2t, when compared with the PCs containing corresponding cis isomers. TUFA-containing PCs also inhibited the enzyme activity competitively, when added to egg PC substrate. The inhibition of LCAT activity was not due to changes in the fluidity of the substrate particle. However, the inhibition depended on the position occupied by TUFA in the PC, as well as on the paired fatty acid. Thus, for human LCAT, 18:1t was more inhibitory when present at sn-2 position of PC, than at sn-1, when paired with 16:0. In contrast, when paired with 20:4, 18:1t was more inhibitory at sn-1 position of PC. Both human and rat LCATs, which are normally specific for the sn-2 acyl group of PC, exhibited an alteration in their positional specificity when 16:0-18:1t PC or 16:1t-20:4 PC was used as substrate, deriving 26-86% of the total acyl groups for cholesterol esterification from the sn-1 position. These results show that the trans fatty acids decrease high density lipoprotein through their inhibition of lecithin: cholesterol acyltransferase (LCAT) activity, and also alter LCAT's positional specificity, inducing the formation of more saturated cholesteryl esters, which are more atherogenic.

iso-Migrastatin, migrastatin, and dorrigocin production in Streptomyces platensis NRRL 18993 is governed by a single biosynthetic machinery featuring an acyltransferase-less type I polyketide synthase.

PubMed

Lim, Si-Kyu; Ju, Jianhua; Zazopoulos, Emmanuel; Jiang, Hui; Seo, Jeong-Woo; Chen, Yihua; Feng, Zhiyang; Rajski, Scott R; Farnet, Chris M; Shen, Ben

2009-10-23

iso-Migrastatin and related glutarimide-containing polyketides are potent inhibitors of tumor cell migration and their implied potential as antimetastatic agents for human cancers has garnered significant attention. Genome scanning of Streptomyces platensis NRRL 18993 unveiled two candidate gene clusters (088D and mgs); each encodes acyltransferase-less type I polyketide synthases commensurate with iso-migrastatin biosynthesis. Both clusters were inactivated by lambda-RED-mediated PCR-targeting mutagenesis in S. platensis; iso-migrastatin production was completely abolished in the DeltamgsF mutant SB11012 strain, whereas inactivation of 088D-orf7 yielded the SB11006 strain that exhibited no discernible change in iso-migrastatin biosynthesis. These data indicate that iso-migrastatin production is governed by the mgs cluster. Systematic gene inactivation allowed determination of the precise boundaries of the mgs cluster and the essentiality of the genes within the mgs cluster in iso-migrastatin production. The mgs cluster consists of 11 open reading frames that encode three acyltransferase-less type I polyketide synthases (MgsEFG), one discrete acyltransferase (MgsH), a type II thioesterase (MgsB), three post-PKS tailoring enzymes (MgsIJK), two glutarimide biosynthesis enzymes (MgsCD), and one regulatory protein (MgsA). A model for iso-migrastatin biosynthesis is proposed based on functional assignments derived from bioinformatics and is further supported by the results of in vivo gene inactivation experiments.

iso-Migrastatin, Migrastatin, and Dorrigocin Production in Streptomyces platensis NRRL 18993 Is Governed by a Single Biosynthetic Machinery Featuring an Acyltransferase-less Type I Polyketide Synthase*

PubMed Central

Lim, Si-Kyu; Ju, Jianhua; Zazopoulos, Emmanuel; Jiang, Hui; Seo, Jeong-Woo; Chen, Yihua; Feng, Zhiyang; Rajski, Scott R.; Farnet, Chris M.; Shen, Ben

2009-01-01

iso-Migrastatin and related glutarimide-containing polyketides are potent inhibitors of tumor cell migration and their implied potential as antimetastatic agents for human cancers has garnered significant attention. Genome scanning of Streptomyces platensis NRRL 18993 unveiled two candidate gene clusters (088D and mgs); each encodes acyltransferase-less type I polyketide synthases commensurate with iso-migrastatin biosynthesis. Both clusters were inactivated by λ-RED-mediated PCR-targeting mutagenesis in S. platensis; iso-migrastatin production was completely abolished in the ΔmgsF mutant SB11012 strain, whereas inactivation of 088D-orf7 yielded the SB11006 strain that exhibited no discernible change in iso-migrastatin biosynthesis. These data indicate that iso-migrastatin production is governed by the mgs cluster. Systematic gene inactivation allowed determination of the precise boundaries of the mgs cluster and the essentiality of the genes within the mgs cluster in iso-migrastatin production. The mgs cluster consists of 11 open reading frames that encode three acyltransferase-less type I polyketide synthases (MgsEFG), one discrete acyltransferase (MgsH), a type II thioesterase (MgsB), three post-PKS tailoring enzymes (MgsIJK), two glutarimide biosynthesis enzymes (MgsCD), and one regulatory protein (MgsA). A model for iso-migrastatin biosynthesis is proposed based on functional assignments derived from bioinformatics and is further supported by the results of in vivo gene inactivation experiments. PMID:19726666

Yeast Gup1(2) Proteins Are Homologues of the Hedgehog Morphogens Acyltransferases HHAT(L): Facts and Implications

PubMed Central

Lucas, Cândida; Ferreira, Célia; Cazzanelli, Giulia; Franco-Duarte, Ricardo; Tulha, Joana

2016-01-01

In multiple tissues, the Hedgehog secreted morphogen activates in the receiving cells a pathway involved in cell fate, proliferation and differentiation in the receiving cells. This pathway is particularly important during embryogenesis. The protein HHAT (Hedgehog O-acyltransferase) modifies Hh morphogens prior to their secretion, while HHATL (Hh O-acyltransferase-like) negatively regulates the pathway. HHAT and HHATL are homologous to Saccharomyces cerevisiae Gup2 and Gup1, respectively. In yeast, Gup1 is associated with a high number and diversity of biological functions, namely polarity establishment, secretory/endocytic pathway functionality, vacuole morphology and wall and membrane composition, structure and maintenance. Phenotypes underlying death, morphogenesis and differentiation are also included. Paracrine signalling, like the one promoted by the Hh pathway, has not been shown to occur in microbial communities, despite the fact that large aggregates of cells like biofilms or colonies behave as proto-tissues. Instead, these have been suggested to sense the population density through the secretion of quorum-sensing chemicals. This review focuses on Gup1/HHATL and Gup2/HHAT proteins. We review the functions and physiology associated with these proteins in yeasts and higher eukaryotes. We suggest standardisation of the presently chaotic Gup-related nomenclature, which includes KIAA117, c3orf3, RASP, Skinny, Sightless and Central Missing, in order to avoid the disclosure of otherwise unnoticed information. PMID:29615596

Diacylglycerol acyltransferase-1 inhibition enhances intestinal fatty acid oxidation and reduces energy intake in rats[S

PubMed Central

Schober, Gudrun; Arnold, Myrtha; Birtles, Susan; Buckett, Linda K.; Pacheco-López, Gustavo; Turnbull, Andrew V.; Langhans, Wolfgang; Mansouri, Abdelhak

2013-01-01

Acyl CoA:diacylglycerol acyltransferase-1 (DGAT-1) catalyzes the final step in triacylglycerol (TAG) synthesis and is highly expressed in the small intestine. Because DGAT-1 knockout mice are resistant to diet-induced obesity, we investigated the acute effects of intragastric (IG) infusion of a small molecule diacylglycerol acyltransferase-1 inhibitor (DGAT-1i) on eating, circulating fat metabolites, indirect calorimetry, and hepatic and intestinal expression of key fat catabolism enzymes in male rats adapted to an 8 h feeding-16 h deprivation schedule. Also, the DGAT-1i effect on fatty acid oxidation (FAO) was investigated in enterocyte cell culture models. IG DGAT-1i infusions reduced energy intake compared with vehicle in high-fat diet (HFD)-fed rats, but scarcely in chow-fed rats. IG DGAT-1i also blunted the postprandial increase in serum TAG and increased β-hydroxybutyrate levels only in HFD-fed rats, in which it lowered the respiratory quotient and increased intestinal, but not hepatic, protein levels of Complex III of the mitochondrial respiratory chain and of mitochondrial hydroxymethylglutaryl-CoA synthase. Finally, the DGAT-1i enhanced FAO in CaCo2 (EC50 = 0.3494) and HuTu80 (EC50 = 0.00762) cells. Thus, pharmacological DGAT-1 inhibition leads to an increase in intestinal FAO and ketogenesis when dietary fat is available. This may contribute to the observed eating-inhibitory effect. PMID:23449193

Recombinant human dihydroxyacetonephosphate acyl-transferase characterization as an integral monotopic membrane protein.

PubMed

Piano, Valentina; Nenci, Simone; Magnani, Francesca; Aliverti, Alessandro; Mattevi, Andrea

2016-12-02

Although the precise functions of ether phospholipids are still poorly understood, significant alterations in their physiological levels are associated either to inherited disorders or to aggressive metastatic cancer. The essential precursor, alkyl-dihydroxyacetone phosphate (DHAP), for all ether phospholipids species is synthetized in two consecutive reactions performed by two enzymes sitting on the inner side of the peroxisomal membrane. Here, we report the characterization of the recombinant human DHAP acyl-transferase, which performs the first step in alkyl-DHAP synthesis. By exploring several expression systems and designing a number of constructs, we were able to purify the enzyme in its active form and we found that it is tightly bound to the membrane through the N-terminal residues. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

Use of Limited Proteolysis and Mutagenesis To Identify Folding Domains and Sequence Motifs Critical for Wax Ester Synthase/Acyl Coenzyme A:Diacylglycerol Acyltransferase Activity

PubMed Central

Villa, Juan A.; Cabezas, Matilde; de la Cruz, Fernando

2014-01-01

Triacylglycerols and wax esters are synthesized as energy storage molecules by some proteobacteria and actinobacteria under stress. The enzyme responsible for neutral lipid accumulation is the bifunctional wax ester synthase/acyl-coenzyme A (CoA):diacylglycerol acyltransferase (WS/DGAT). Structural modeling of WS/DGAT suggests that it can adopt an acyl-CoA-dependent acyltransferase fold with the N-terminal and C-terminal domains connected by a helical linker, an architecture demonstrated experimentally by limited proteolysis. Moreover, we found that both domains form an active complex when coexpressed as independent polypeptides. The structural prediction and sequence alignment of different WS/DGAT proteins indicated catalytically important motifs in the enzyme. Their role was probed by measuring the activities of a series of alanine scanning mutants. Our study underscores the structural understanding of this protein family and paves the way for their modification to improve the production of neutral lipids. PMID:24296496

Putative DHHC-Cysteine-Rich Domain S-Acyltransferase in Plants

PubMed Central

Sun, Meihong; Liu, Shiyang; Qi, Baoxiu; Li, Xinzheng

2013-01-01

Protein S-acyltransferases (PATs) containing Asp-His-His-Cys within a Cys-rich domain (DHHC-CRD) are polytopic transmembrane proteins that are found in eukaryotic cells and mediate the S-acylation of target proteins. S-acylation is an important secondary and reversible modification that regulates the membrane association, trafficking and function of target proteins. However, little is known about the characteristics of PATs in plants. Here, we identified 804 PATs from 31 species with complete genomes. The analysis of the phylogenetic relationships suggested that all of the PATs fell into 8 groups. In addition, we analysed the phylogeny, genomic organization, chromosome localisation and expression pattern of PATs in Arabidopsis, Oryza sative, Zea mays and Glycine max. The microarray data revealed that PATs genes were expressed in different tissues and during different life stages. The preferential expression of the ZmPATs in specific tissues and the response of Zea mays to treatments with phytohormones and abiotic stress demonstrated that the PATs play roles in plant growth and development as well as in stress responses. Our data provide a useful reference for the identification and functional analysis of the members of this protein family. PMID:24155879

Identification of conserved regions and residues within Hedgehog acyltransferase critical for palmitoylation of Sonic Hedgehog.

PubMed

Buglino, John A; Resh, Marilyn D

2010-06-23

Sonic hedgehog (Shh) is a palmitoylated protein that plays key roles in mammalian development and human cancers. Palmitoylation of Shh is required for effective long and short range Shh-mediated signaling. Attachment of palmitate to Shh is catalyzed by Hedgehog acyltransferase (Hhat), a member of the membrane bound O-acyl transferase (MBOAT) family of multipass membrane proteins. The extremely hydrophobic composition of MBOAT proteins has limited their biochemical characterization. Except for mutagenesis of two conserved residues, there has been no structure-function analysis of Hhat, and the regions of the protein required for Shh palmitoylation are unknown. Here we undertake a systematic approach to identify residues within Hhat that are required for protein stability and/or enzymatic activity. We also identify a second, novel MBOAT homology region (residues 196-234) that is required for Hhat activity. In total, ten deletion mutants and eleven point mutants were generated and analyzed. Truncations at the N- and C-termini of Hhat yielded inactive proteins with reduced stability. Four Hhat mutants with deletions within predicted loop regions and five point mutants retained stability but lost palmitoylation activity. We purified two point mutants, W378A and H379A, with defective Hhat activity. Kinetic analyses revealed alterations in apparent K(m) and V(max) for Shh and/or palmitoyl CoA, changes that likely explain the catalytic defects observed for these mutants. This study has pinpointed specific regions and multiple residues that regulate Hhat stability and catalysis. Our findings should be applicable to other MBOAT proteins that mediate lipid modification of Wnt proteins and ghrelin, and should serve as a model for understanding how secreted morphogens are modified by palmitoyl acyltransferases.

The role of acyl-CoA:diacylglycerol acyltransferase (DGAT) in energy metabolism.

PubMed

Yu, Yi-Hao; Ginsberg, Henry N

2004-01-01

Acyl-CoA:diacylglycerol acyltransferase (DGAT, EC2.3.1.20), a key enzyme in triglyceride (TG) biosynthesis, not only participates in lipid metabolism but also influences metabolic pathways of other fuel molecules. Changes in the expression and/or activity levels of DGAT may lead to changes in systemic insulin sensitivity and energy homeostasis. The synthetic role of DGAT in adipose tissue, the liver, and the intestine, sites where endogenous levels of DGAT activity and TG synthesis are high, is relatively clear. Less clear is whether DGAT plays a mediating or preventive role in the development of ectopic lipotoxicity in tissues such as muscle and the pancreas, when their supply of free fatty acids (FFAs) exceeds their needs. Future studies with tissue-specific overexpression and/or knockout in these animal models would be expected to shed additional light on these issues.

Therapeutic strategies for metabolic diseases: Small-molecule diacylglycerol acyltransferase (DGAT) inhibitors.

PubMed

Naik, Ravi; Obiang-Obounou, Brice W; Kim, Minkyoung; Choi, Yongseok; Lee, Hyun Sun; Lee, Kyeong

2014-11-01

Metabolic diseases such as atherogenic dyslipidemia, hepatic steatosis, obesity, and type II diabetes are emerging as major global health problems. Acyl-CoA:diacylglycerol acyltransferase (DGAT) is responsible for catalyzing the final reaction in the glycerol phosphate pathway of triglycerol synthesis. It has two isoforms, DGAT-1 and DGAT-2, which are widely expressed and present in white adipose tissue. DGAT-1 is most highly expressed in the small intestine, whereas DGAT-2 is primarily expressed in the liver. Therefore, the selective inhibition of DGAT-1 has become an attractive target with growing potential for the treatment of obesity and type II diabetes. Furthermore, DGAT-2 has been suggested as a new target for the treatment of DGAT-2-related liver diseases including hepatic steatosis, hepatic injury, and fibrosis. In view the discovery of drugs that target DGAT, herein we attempt to provide insight into the scope and further reasons for optimization of DGAT inhibitors. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Diacylglycerol Acyltransferase-1 (DGAT1) Inhibition Perturbs Postprandial Gut Hormone Release

PubMed Central

Lin, Hua V.; Chen, Dunlu; Shen, Zhu; Zhu, Lei; Ouyang, Xuesong; Vongs, Aurawan; Kan, Yanqing; Levorse, John M.; Kowalik, Edward J.; Szeto, Daphne M.; Yao, Xiaorui; Xiao, Jianying; Chen, Shirley; Liu, Jinqi; Garcia-Calvo, Marga; Shin, Myung K.; Pinto, Shirly

2013-01-01

Diacylglycerol acyltransferase-1 (DGAT1) is a potential therapeutic target for treatment of obesity and related metabolic diseases. However, the degree of DGAT1 inhibition required for metabolic benefits is unclear. Here we show that partial DGAT1 deficiency in mice suppressed postprandial triglyceridemia, led to elevations in glucagon-like peptide-1 (GLP-1) and peptide YY (PYY) only following meals with very high lipid content, and did not protect from diet-induced obesity. Maximal DGAT1 inhibition led to enhanced GLP-1 and PYY secretion following meals with physiologically relevant lipid content. Finally, combination of DGAT1 inhibition with dipeptidyl-peptidase-4 (DPP-4) inhibition led to further enhancements in active GLP-1 in mice and dogs. The current study suggests that targeting DGAT1 to enhance postprandial gut hormone secretion requires maximal inhibition, and suggests combination with DPP-4i as a potential strategy to develop DGAT1 inhibitors for treatment of metabolic diseases. PMID:23336002

Mice Deficient in lysophosphatidic acid acyltransferase delta (Lpaatδ)/acylglycerophosphate acyltransferase 4 (Agpat4) Have Impaired Learning and Memory.

PubMed

Bradley, Ryan M; Mardian, Emily B; Bloemberg, Darin; Aristizabal Henao, Juan J; Mitchell, Andrew S; Marvyn, Phillip M; Moes, Katherine A; Stark, Ken D; Quadrilatero, Joe; Duncan, Robin E

2017-11-15

We previously characterized LPAATδ/AGPAT4 as a mitochondrial lysophosphatidic acid acyltransferase that regulates brain levels of phosphatidylcholine (PC), phosphatidylethanolamine (PE), and phosphatidylinositol (PI). Here, we report that Lpaat δ -/- mice display impaired spatial learning and memory compared to wild-type littermates in the Morris water maze and our investigation of potential mechanisms associated with brain phospholipid changes. Marker protein immunoblotting suggested that the relative brain content of neurons, glia, and oligodendrocytes was unchanged. Relative abundance of the important brain fatty acid docosahexaenoic acid was also unchanged in phosphatidylserine, phosphatidylglycerol, and cardiolipin, in agreement with prior data on PC, PE and PI. In phosphatidic acid, it was increased. Specific decreases in ethanolamine-containing phospholipids were detected in mitochondrial lipids, but the function of brain mitochondria in Lpaat δ -/- mice was unchanged. Importantly, we found that Lpaat δ -/- mice have a significantly and drastically lower brain content of the N -methyl-d-asparate (NMDA) receptor subunits NR1, NR2A, and NR2B, as well as the α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor subunit GluR1, compared to wild-type mice. However, general dysregulation of PI-mediated signaling is not likely responsible, since phospho-AKT and phospho-mTOR pathway regulation was unaffected. Our findings indicate that Lpaat δ deficiency causes deficits in learning and memory associated with reduced NMDA and AMPA receptors. Copyright © 2017 American Society for Microbiology.

Discovery of a new mechanism for regulation of plant triacylglycerol metabolism: The peanut diacylglycerol acyltransferase-1 gene family transcriptome is highly enriched in alternative splicing variants

USDA-ARS?s Scientific Manuscript database

Triacylglycerols (TAGs) are the most important energy storage form in oilseed crops. Diacylglycerol acyltransferase (DGAT) catalyzes the rate-limiting step of the Kennedy pathway of TAG biosynthesis. To date, little is known about the regulation of DGAT activity in peanut (Arachis hypogaea), an agr...

Reversible Lysine Acetylation Regulates Activity of Human Glycine N-Acyltransferase-like 2 (hGLYATL2)

PubMed Central

Waluk, Dominik P.; Sucharski, Filip; Sipos, Laszlo; Silberring, Jerzy; Hunt, Mary C.

2012-01-01

Lysine acetylation is a major post-translational modification of proteins and regulates many physiological processes such as metabolism, cell migration, aging, and inflammation. Proteomic studies have identified numerous lysine-acetylated proteins in human and mouse models (Kim, S. C., Sprung, R., Chen, Y., Xu, Y., Ball, H., Pei, J., Cheng, T., Kho, Y., Xiao, H., Xiao, L., Grishin, N. V., White, M., Yang, X. J., and Zhao, Y. (2006) Mol. Cell 23, 607–618). One family of proteins identified in this study was the murine glycine N-acyltransferase (GLYAT) enzymes, which are acetylated on lysine 19. Lysine 19 is a conserved residue in human glycine N-acyltransferase-like 2 (hGLYATL2) and in several other species, showing that this residue may be important for enzyme function. Mutation of lysine 19 in recombinant hGLYATL2 to glutamine (K19Q) and arginine (K19R) resulted in a 50–80% lower production of N-oleoyl glycine and N-arachidonoylglycine, indicating that lysine 19 is important for enzyme function. LC/MS/MS confirmed that Lys-19 is not acetylated in wild-type hGLYATL2, indicating that Lys-19 requires to be deacetylated for full activity. The hGLYATL2 enzyme conjugates medium- and long-chain saturated and unsaturated acyl-CoA esters to glycine, resulting in the production of N-oleoyl glycine and also N-arachidonoyl glycine. N-Oleoyl glycine and N-arachidonoyl glycine are structurally and functionally related to endocannabinoids and have been identified as signaling molecules that regulate functions like the perception of pain and body temperature and also have anti-inflammatory properties. In conclusion, acetylation of lysine(s) in hGLYATL2 regulates the enzyme activity, thus linking post-translational modification of proteins with the production of biological signaling molecules, the N-acyl glycines. PMID:22408254

Diacylglycerol Acyltransferase 1 Is Regulated by Its N-Terminal Domain in Response to Allosteric Effectors.

PubMed

Caldo, Kristian Mark P; Acedo, Jeella Z; Panigrahi, Rashmi; Vederas, John C; Weselake, Randall J; Lemieux, M Joanne

2017-10-01

Diacylglycerol acyltransferase 1 (DGAT1) is an integral membrane enzyme catalyzing the final and committed step in the acyl-coenzyme A (CoA)-dependent biosynthesis of triacylglycerol (TAG). The biochemical regulation of TAG assembly remains one of the least understood areas of primary metabolism to date. Here, we report that the hydrophilic N-terminal domain of Brassica napus DGAT1 (BnaDGAT1 1-113 ) regulates activity based on acyl-CoA/CoA levels. The N-terminal domain is not necessary for acyltransferase activity and is composed of an intrinsically disordered region and a folded segment. We show that the disordered region has an autoinhibitory function and a dimerization interface, which appears to mediate positive cooperativity, whereas the folded segment of the cytosolic region was found to have an allosteric site for acyl-CoA/CoA. Under increasing acyl-CoA levels, the binding of acyl-CoA with this noncatalytic site facilitates homotropic allosteric activation. Enzyme activation, on the other hand, is prevented under limiting acyl-CoA conditions (low acyl-CoA-to-CoA ratio), whereby CoA acts as a noncompetitive feedback inhibitor through interaction with the same folded segment. The three-dimensional NMR solution structure of the allosteric site revealed an α-helix with a loop connecting a coil fragment. The conserved amino acid residues in the loop interacting with CoA were identified, revealing details of this important regulatory element for allosteric regulation. Based on these results, a model is proposed illustrating the role of the N-terminal domain of BnaDGAT1 as a positive and negative modulator of TAG biosynthesis. © 2017 American Society of Plant Biologists. All Rights Reserved.

Cloning of a coconut endosperm cDNA encoding a 1-acyl-sn-glycerol-3-phosphate acyltransferase that accepts medium-chain-length substrates.

PubMed Central

Knutzon, D S; Lardizabal, K D; Nelsen, J S; Bleibaum, J L; Davies, H M; Metz, J G

1995-01-01

Immature coconut (Cocos nucifera) endosperm contains a 1-acyl-sn-glycerol-3-phosphate acyltransferase (LPAAT) activity that shows a preference for medium-chain-length fatty acyl-coenzyme A substrates (H.M. Davies, D.J. Hawkins, J.S. Nelsen [1995] Phytochemistry 39:989-996). Beginning with solubilized membrane preparations, we have used chromatographic separations to identify a polypeptide with an apparent molecular mass of 29 kD, whose presence in various column fractions correlates with the acyltransferase activity detected in those same fractions. Amino acid sequence data obtained from several peptides generated from this protein were used to isolate a full-length clone from a coconut endosperm cDNA library. Clone pCGN5503 contains a 1325-bp cDNA insert with an open reading frame encoding a 308-amino acid protein with a calculated molecular mass of 34.8 kD. Comparison of the deduced amino acid sequence of pCGN5503 to sequences in the data banks revealed significant homology to other putative LPAAT sequences. Expression of the coconut cDNA in Escherichia coli conferred upon those cells a novel LPAAT activity whose substrate activity profile matched that of the coconut enzyme. PMID:8552723

Genetic variation of the ghrelin activator gene ghrelin O-acyltransferase (GOAT) is associated with anorexia nervosa.

PubMed

Müller, Timo D; Tschöp, Matthias H; Jarick, Ivonne; Ehrlich, Stefan; Scherag, Susann; Herpertz-Dahlmann, Beate; Zipfel, Stefan; Herzog, Wolfgang; de Zwaan, Martina; Burghardt, Roland; Fleischhaker, Christian; Klampfl, Karin; Wewetzer, Christoph; Herpertz, Stephan; Zeeck, Almut; Tagay, Sefik; Burgmer, Markus; Pfluger, Paul T; Scherag, André; Hebebrand, Johannes; Hinney, Anke

2011-05-01

The gastrointestinal peptide hormone ghrelin promotes food intake and increases body weight and adiposity through activation of the growth hormone secretagogue receptor (GHSR1a). To promote its biological action ghrelin is acylated at its serine 3 residue by the recently discovered ghrelin O-acyltransferase (GOAT, a.k.a. membrane-bound O-acyltransferase 4, MBOAT4). Plasma levels of total and acyl-ghrelin are negatively correlated with body-mass-index (BMI); as lower the BMI as higher plasma levels of total and acylated ghrelin and vice versa. Accordingly, plasma levels of total and acyl-ghrelin are elevated in patients with anorexia nervosa (AN) and decline upon weight regain. The importance of the endogenous Goat/ghrelin system in the neuroendocrine adaptation to fasting was recently highlighted by the observation that acyl-ghrelin mediated elevation of growth hormone (GH) release prevents starvation induced hypoglycemia in Goat(-/-) mice. The aim of this study was to test if genetic variation of GOAT is implicated in the etiology of AN. We therefore assessed association of 6 tagging single nucleotide polymorphisms (tagSNPs), which were predicted to cover 96% the common genetic variability of GOAT plus 50 kb of the 5' and 3' flanking region, in 543 German patients with AN and 612 German normal and underweight healthy controls. Based on a recessive mode of inheritance we observed some evidence for association of the G/G genotype at SNP rs10096097 with AN (nominal two-sided p = 0.031). Based on our results we conclude that genetic variation in GOAT might be implicated in the etiology of AN. Copyright © 2010 Elsevier Ltd. All rights reserved.

Mammalian Wax Biosynthesis

PubMed Central

Cheng, Jeffrey B.; Russell, David W.

2009-01-01

Wax monoesters are synthesized by the esterification of fatty alcohols and fatty acids. A mammalian enzyme that catalyzes this reaction has not been isolated. We used expression cloning to identify cDNAs encoding a wax synthase in the mouse preputial gland. The wax synthase gene is located on the X chromosome and encodes a member of the acyltransferase family of enzymes that synthesize neutral lipids. Expression of wax synthase in cultured cells led to the formation of wax monoesters from straight chain saturated, unsaturated, and polyunsaturated fatty alcohols and acids. Polyisoprenols also were incorporated into wax monoesters by the enzyme. The wax synthase had little or no ability to synthesize cholesteryl esters, diacylglycerols, or triacylglycerols, whereas other acyltransferases, including the acyl-CoA:monoacylglycerol acyltransferase 1 and 2 enzymes and the acyl-CoA:diacylglycerol acyltransferase 1 and 2 enzymes, exhibited modest wax monoester synthesis activities. Confocal light microscopy indicated that the wax synthase was localized in membranes of the endoplasmic reticulum. Wax synthase mRNA was abundant in tissues rich in sebaceous glands such as the preputial gland and eyelid and was present at lower levels in other tissues. Coexpression of cDNAs specifying fatty acyl-CoA reductase 1 and wax synthase led to the synthesis of wax monoesters. The data suggest that wax monoester synthesis in mammals involves a two step biosynthetic pathway catalyzed by fatty acyl-CoA reductase and wax synthase enzymes. PMID:15220349

Stereochemical and positional specificity of the lipase/acyltransferase produced by Aeromonas hydrophila.

PubMed

Robertson, D L; Hilton, S; Buckley, J T

1992-06-02

Aeromonas species secrete a glycerophospholipid-cholesterol acyltransferase (GCAT) which shares many properties with mammalian plasma lecithin-cholesterol acetyltransferase (LCAT). We have studied the stereochemical and positional specificity of GCAT against a variety of lipid substrates using NMR spectroscopy as well as other assay methods. The results show that both the primary and secondary acyl ester bonds of L-phosphatidylcholine can be hydrolyzed but only the sn-2 fatty acid can be transferred to cholesterol. The enzyme has an absolute requirement for the L configuration at the sn-2 position of phosphatidylcholine. The secondary ester bond of D-phosphatidylcholine cannot be hydrolyzed, and this lipid is not a substrate for acyl transfer. In contrast to the phospholipases, but similar to LCAT, the enzyme does not interact stereochemically with the phosphorus of phosphatidylcholine. In fact, the phosphorus is not required for enzyme activity, as GCAT will also hydrolyze monolayers of diglyceride, although at much lower rates.

Structure and function of lysosomal phospholipase A2 and lecithin:cholesterol acyltransferase

NASA Astrophysics Data System (ADS)

Glukhova, Alisa; Hinkovska-Galcheva, Vania; Kelly, Robert; Abe, Akira; Shayman, James A.; Tesmer, John J. G.

2015-03-01

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. Insertions in the α/β hydrolase core of LPLA2 form domains that are responsible for membrane interaction and binding the acyl chains and head groups of phospholipid substrates. The LCAT structure suggests the molecular basis underlying human disease for most of the known LCAT missense mutations, and paves the way for rational development of new therapeutics to treat LCAT deficiency, atherosclerosis and acute coronary syndrome.

Mycobacterial polyketide-associated proteins are acyltransferases: Proof of principle with Mycobacterium tuberculosis PapA5

PubMed Central

Onwueme, Kenolisa C.; Ferreras, Julian A.; Buglino, John; Lima, Christopher D.; Quadri, Luis E. N.

2004-01-01

Mycobacterium tuberculosis (Mt) produces complex virulence-enhancing lipids with scaffolds consisting of phthiocerol and phthiodiolone dimycocerosate esters (PDIMs). Sequence analysis suggested that PapA5, a so-called polyketide-associated protein (Pap) encoded in the PDIM synthesis gene cluster, as well as PapA5 homologs found in Mt and other species, are a subfamily of acyltransferases. Studies with recombinant protein confirmed that PapA5 is an acetyltransferase. Deletion analysis in Mt demonstrated that papA5 is required for PDIM synthesis. We propose that PapA5 catalyzes diesterification of phthiocerol and phthiodiolone with mycocerosate. These studies present the functional characterization of a Pap and permit inferences regarding roles of other Paps in the synthesis of complex lipids, including the antibiotic rifamycin. PMID:15070765

Sex and depot differences in ex vivo adipose tissue fatty acid storage and glycerol-3-phosphate acyltransferase activity

PubMed Central

Morgan-Bathke, Maria; Chen, Liang; Oberschneider, Elisabeth; Harteneck, Debra

2015-01-01

Adipose tissue fatty acid storage varies according to sex, adipose tissue depot, and degree of fat gain. However, the mechanism(s) for these variations is not completely understood. We examined whether differences in adipose tissue glycerol-3-phosphate acyltransferase (GPAT) might play a role in these variations. We optimized an enzyme activity assay for total GPAT and GPAT1 activity in human adipose tissue and measured GPAT activity. Omental and subcutaneous adipose tissue was collected from obese and nonobese adults for measures of GPAT and GPAT1 activities, ex vivo palmitate storage, acyl-CoA synthetase (ACS) and diacylglycerol-acyltransferase (DGAT) activities, and CD36 protein. Total GPAT and GPAT1 activities decreased as a function of adipocyte size in both omental (r = −0.71, P = 0.003) and subcutaneous (r = −0.58, P = 0.04) fat. The relative contribution of GPAT1 to total GPAT activity increased as a function of adipocyte size, accounting for up to 60% of GPAT activity in those with the largest adipocytes. We found strong, positive correlations between ACS, GPAT, and DGAT activities for both sexes and depots (r values 0.58–0.91) and between these storage factors and palmitate storage rates into TAG (r values 0.55–0.90). We conclude that: 1) total GPAT activity decreases as a function of adipocyte size; 2) GPAT1 can account for over half of adipose GPAT activity in hypertrophic obesity; and 3) ACS, GPAT, and DGAT are coordinately regulated. PMID:25738782

Screening of adjunct cultures and their application in ester formation in Camembert-type cheese.

PubMed

Hong, Q; Liu, X M; Hang, F; Zhao, J X; Zhang, H; Chen, W

2018-04-01

The ethanol content and esterase and alcohol acyltransferase activities are the limiting factors in the synthesis of ethyl esters in Camembert-type cheeses. This study aimed to investigate the effects of alcohol, esterase and alcohol acyltransferase activities on ethyl ester formation in Camembert-type cheeses. Five experimental cheeses were prepared with three adjunct cultures with different enzyme activities and two levels of ethanol content (400 or 800 μg/g). The cheeses were aged for 4 weeks and analysed weekly for basic physicochemical, textural, volatile and sensory properties. The results showed that both the enzyme activity and ethanol content were limiting factors in the synthesis of ethyl esters in the Camembert-type cheeses. Variation in the esterase synthesis activity was observed among lactic acid bacteria, and the starter culture Lactococcus lactis MA 14 LYO distinguished itself through its high acidifying and esterase hydrolysis abilities. The addition of CCFM 12, a lactic acid bacteria strain with high esterase and alcohol acyltransferase activity, along with 400 or 800 μg/g of ethanol, notably enhanced the generation of ethyl esters and the corresponding fruity flavour, without causing dramatic changes in the basic physicochemical indices and microbial profile. In addition, cohesiveness was influenced by the addition of 400 and 800 μg/g of ethanol, and more resilience with 800 μg/g of ethanol had been found. The results showed that the addition of CCFM12 with 400 and 800 μg/g of ethanol may be applied in the production of Camembert cheese to enhance its fruity flavour. Copyright © 2017 Elsevier Ltd. All rights reserved.

Isolation and identification of lutein esters, including their regioisomers, in tritordeum (×Tritordeum Ascherson et Graebner) grains: Evidence for a preferential xanthophyll acyltransferase activity.

PubMed

Mellado-Ortega, Elena; Hornero-Méndez, Dámaso

2012-12-01

Liquid chromatography in conjunction with UV-visible spectroscopy and atmospheric pressure chemical ionisation (APCI) mass spectrometry has been used for the structural assignment of the lutein esters, including the regioisomeric forms, naturally occurring in the endosperm of tritordeum (×Tritordeum Ascherson et Graebner), a novel cereal. The distinctive mass spectrometry fragmentation pattern of lutein, characterized by a favored loss of the moieties at the position 3' of the ε-end ring, allowed an unambiguous structural identification of four monoesters (lutein 3'-O-linoleate, lutein 3-O-linoleate, lutein 3'-O-palmitate, lutein 3-O-palmitate) and four diesters (lutein dilinoleate, lutein 3'-O-linoleate-3-O-palmitate, lutein 3'-O-palmitate-3-O-linoleate, lutein dipalmitate). This is the first time that the regioisomers of carotenoid esters have been identified in a cereal. Evidences for a preferential xanthophyll acyltransferase activity regarding the position (3 or 3') and the acyl moiety are discussed. Further studies should be carried out in order to identify the acyltransferase enzymes and the acyl donor molecules involved in the xanthophyll esterification process. Copyright © 2012 Elsevier Ltd. All rights reserved.

Analysis of substrate specificity of human DHHC protein acyltransferases using a yeast expression system

PubMed Central

Ohno, Yusuke; Kashio, Atsushi; Ogata, Ren; Ishitomi, Akihiro; Yamazaki, Yuki; Kihara, Akio

2012-01-01

Palmitoylation plays important roles in the regulation of protein localization, stability, and activity. The protein acyltransferases (PATs) have a common DHHC Cys-rich domain. Twenty-three DHHC proteins have been identified in humans. However, it is unclear whether all of these DHHC proteins function as PATs. In addition, their substrate specificities remain largely unknown. Here we develop a useful method to examine substrate specificities of PATs using a yeast expression system with six distinct model substrates. We identify 17 human DHHC proteins as PATs. Moreover, we classify 11 human and 5 yeast DHHC proteins into three classes (I, II, and III), based on the cellular localization of their respective substrates (class I, soluble proteins; class II, integral membrane proteins; class III, lipidated proteins). Our results may provide an important clue for understanding the function of individual DHHC proteins. PMID:23034182

The Last Step in Cocaine Biosynthesis Is Catalyzed by a BAHD Acyltransferase[OPEN

PubMed Central

Schmidt, Gregor Wolfgang; Porta, Tiffany; Reichelt, Michael; Luck, Katrin; Torre, José Carlos Pardo; Dolke, Franziska; Varesio, Emmanuel; Hopfgartner, Gérard; Gershenzon, Jonathan

2015-01-01

The esterification of methylecgonine (2-carbomethoxy-3β-tropine) with benzoic acid is the final step in the biosynthetic pathway leading to the production of cocaine in Erythoxylum coca. Here we report the identification of a member of the BAHD family of plant acyltransferases as cocaine synthase. The enzyme is capable of producing both cocaine and cinnamoylcocaine via the activated benzoyl- or cinnamoyl-Coenzyme A thioesters, respectively. Cocaine synthase activity is highest in young developing leaves, especially in the palisade parenchyma and spongy mesophyll. These data correlate well with the tissue distribution pattern of cocaine as visualized with antibodies. Matrix-assisted laser-desorption ionization mass spectral imaging revealed that cocaine and cinnamoylcocaine are differently distributed on the upper versus lower leaf surfaces. Our findings provide further evidence that tropane alkaloid biosynthesis in the Erythroxylaceae occurs in the above-ground portions of the plant in contrast with the Solanaceae, in which tropane alkaloid biosynthesis occurs in the roots. PMID:25406120

Identification and Characterization of Diacylglycerol Acyltransferase from Oleaginous Fungus Mucor circinelloides.

PubMed

Zhang, Luning; Zhang, Huaiyuan; Song, Yuanda

2018-01-24

Acyl-CoA:diacylglycerol acyltransferase (DGAT) is a pivotal regulator of triacylglycerol (TAG) synthesis. The oleaginous fungus Mucor circinelloides has four putative DGATs: McDGAT1A, McDGAT1B, McDGAT2A, and McDGAT2B, classified into the DGAT1 and DGAT2 subfamilies, respectively. To identify and characterize DGATs in M. circinelloides, these four genes were expressed in Saccharomyces cerevisiae H1246 (TAG-deficient quadruple mutant), individually. TAG biosynthesis was restored only by the expression of McDGAT2B, and TAG content was significantly higher in the mutants with McDGAT2B expression than in a S. cerevisiae mutant with endogenous DGA1 expression. McDGAT2B prefers saturated fatty acids to monounsaturated fatty acids and has an obvious preference for C18:3 (ω-6) according to the results of substrate preference experiments. Furthermore, only the mRNA expression pattern of McDGAT2B correlated with TAG biosynthesis during a fermentation process. Our experiments strongly indicate that McDGAT2B is crucial for TAG accumulation, suggesting that it may be an essential target for metabolic engineering aimed at increasing lipid content of M. circinelloides.

The Arabidopsis DCR encoding a soluble BAHD acyltransferase is required for cutin polyester formation and seed hydration properties.

PubMed

Panikashvili, David; Shi, Jian Xin; Schreiber, Lukas; Aharoni, Asaph

2009-12-01

The cuticle covering every plant aerial organ is largely made of cutin that consists of fatty acids, glycerol, and aromatic monomers. Despite the huge importance of the cuticle to plant development and fitness, our knowledge regarding the assembly of the cutin polymer and its integration in the complete cuticle structure is limited. Cutin composition implies the action of acyltransferase-type enzymes that mediate polymer construction through ester bond formation. Here, we show that a member of the BAHD family of acyltransferases (DEFECTIVE IN CUTICULAR RIDGES [DCR]) is required for incorporation of the most abundant monomer into the polymeric structure of the Arabidopsis (Arabidopsis thaliana) flower cutin. DCR-deficient plants display phenotypes that are typically associated with a defective cuticle, including altered epidermal cell differentiation and postgenital organ fusion. Moreover, levels of the major cutin monomer in flowers, 9(10),16-dihydroxy-hexadecanoic acid, decreased to an almost undetectable amount in the mutants. Interestingly, dcr mutants exhibit changes in the decoration of petal conical cells and mucilage extrusion in the seed coat, both phenotypes formerly not associated with cutin polymer assembly. Excessive root branching displayed by dcr mutants and the DCR expression pattern in roots pointed to the function of DCR belowground, in shaping root architecture by influencing lateral root emergence and growth. In addition, the dcr mutants were more susceptible to salinity, osmotic, and water deprivation stress conditions. Finally, the analysis of DCR protein localization suggested that cutin polymerization, possibly the oligomerization step, is partially carried out in the cytoplasmic space. Therefore, this study extends our knowledge regarding the functionality of the cuticular layer and the formation of its major constituent the polymer cutin.

Phospholipid:diacylglycerol acyltransferase-mediated triacylglycerol biosynthesis is crucial for protection against fatty acid-induced cell death in growing tissues of Arabidopsis.

PubMed

Fan, Jilian; Yan, Chengshi; Xu, Changcheng

2013-12-01

Phospholipid:diacylglycerol acyltransferase (PDAT) and diacylglycerol:acyl CoA acyltransferase play overlapping roles in triacylglycerol (TAG) assembly in Arabidopsis, and are essential for seed and pollen development, but the functional importance of PDAT in vegetative tissues remains largely unknown. Taking advantage of the Arabidopsis tgd1-1 mutant that accumulates oil in vegetative tissues, we demonstrate here that PDAT1 is crucial for TAG biosynthesis in growing tissues. We show that disruption of PDAT1 in the tgd1-1 mutant background causes serious growth retardation, gametophytic defects and premature cell death in developing leaves. Lipid analysis data indicated that knockout of PDAT1 results in increases in the levels of free fatty acids (FFAs) and diacylglycerol. In vivo ¹⁴C-acetate labeling experiments showed that, compared with wild-type, tgd1-1 exhibits a 3.8-fold higher rate of fatty acid synthesis (FAS), which is unaffected by disruption or over-expression of PDAT1, indicating a lack of feedback regulation of FAS in tgd1-1. We also show that detached leaves of both pdat1-2 and tgd1-1 pdat1-2 display increased sensitivity to FFA but not to diacylglycerol. Taken together, our results reveal a critical role for PDAT1 in mediating TAG synthesis and thereby protecting against FFA-induced cell death in fast-growing tissues of plants. © 2013 The Authors The Plant Journal © 2013 John Wiley & Sons Ltd.

Role of glycerol 3-phosphate and glycerophosphate acyltransferase in the nutritional control of hepatic triacylglycerol synthesis

PubMed Central

Declercq, Peter E.; Debeer, Luc J.; Mannaerts, Guy P.

1982-01-01

1. Glycerol 3-phosphate content of isolated hepatocytes from starved rats and of glycogen-depleted hepatocytes from fed rats was low and severely limited triacylglycerol synthesis. 2. Raising the glycerol 3-phosphate content by addition of precursors to the cells resulted in a hyperbolic-like relationship between triacylglycerol synthesis and cellular glycerol 3-phosphate content. Statistical analysis of the curves showed no significant differences between the nutritional states either at saturating or at subsaturating glycerol 3-phosphate content. 3. Vmax. of glycerophosphate acyltransferase measured in homogenized hepatocytes was decreased by 30–40% in starvation. There was no change in apparent Km for glycerol 3-phosphate. Since at saturating glycerol 3-phosphate content esterification rates in hepatocytes of both nutritional states were identical, the enzyme is not limiting esterification under this condition. 4. At subsaturating glycerol 3-phosphate content the flux through glycerophosphate acyltransferase necessarily limits esterification. Therefore one would expect a decrease in esterification in starvation under this condition. This was the case when triacylglycerol synthesis was plotted against intracellular glycerol 3-phosphate concentration, calculated from the cellular glycerol 3-phosphate content and the intracellular water space, which was smaller in hepatocytes from starved rats. 5. The data obtained in hepatocytes were extrapolated to the intact liver by using the number of parenchymal cells per g of liver as determined from marker-enzyme analysis and the liver weight per 100g body weight. The extrapolation suggested that glycerol 3-phosphate is limiting esterification in vivo for contents below 0.3–0.4 and 0.5–0.65μmol/g for livers from fed and starved animals respectively. Also for a given fatty acid load and a glycerol 3-phosphate content below 0.3μmol/g the liver may esterify less in the starved state. However, at the glycerol 3

Disparate effects of oxidation on plasma acyltransferase activities: inhibition of cholesterol esterification but stimulation of transesterification of oxidized phospholipids.

PubMed

Subbaiah, P V; Liu, M

1996-05-31

Oxidation of lipoproteins results in the formation of several polar phospholipids with pro-inflammatory and pro-atherogenic properties. To examine the possible role of lecithin/cholesterol acyltransferase (LCAT) in the metabolism of these oxidized phospholipids, we oxidized whole plasma with either Cu(2+) or a free-radical generator, and determined the various activities of LCAT. Oxidation caused a reduction in plasma phosphatidylcholine (PC), an increase in a short-chain polar PC (SCP-PC), and an inhibition of the transfer of long-chain acyl groups to cholesterol (LCAT activity) or to lyso PC (lysolecithin acyltransferase (LAT) I activity). However, the transfer of short-chain acyl groups from SCP-PC to lyso PCLAT II activity) was stimulated several fold, in direct correlation with the degree of oxidation. LAT II activity was not stimulated by oxidation in LCAT-deficient plasma, showing that it is carried out by LCAT. Oxidized normal plasma exhibited low LCAT activity even in the presence of exogenous proteoliposome substrate, indicating that the depletion of substrate PC was not responsible for the loss of activity. Oxidation of isolated LDL or HDL abolished their ability to support LCAT and LAT I activities of exogenous enzyme, but promoted the LAT II activity. Purified LCAT lost its LCAT and LAT I functions, but not its LAT II function, when oxidized in vitro. These results show that while oxidation of plasma causes a loss of LCAT's ability to transfer long-chain acyl groups, its ability to transfer short-chain acyl groups, from SCP-PC is retained, and even stimulated, suggesting that LCAT may have a physiological role in the metabolism of oxidized PC in plasma.

Fas palmitoylation by the palmitoyl acyltransferase DHHC7 regulates Fas stability

PubMed Central

Rossin, A; Durivault, J; Chakhtoura-Feghali, T; Lounnas, N; Gagnoux-Palacios, L; Hueber, A-O

2015-01-01

The death receptor Fas undergoes a variety of post-translational modifications including S-palmitoylation. This protein acylation has been reported essential for an optimal cell death signaling by allowing both a proper Fas localization in cholesterol and sphingolipid-enriched membrane nanodomains, as well as Fas high-molecular weight complexes. In human, S-palmitoylation is controlled by 23 members of the DHHC family through their palmitoyl acyltransferase activity. In order to better understand the role of this post-translational modification in the regulation of the Fas-mediated apoptosis pathway, we performed a screen that allowed the identification of DHHC7 as a Fas-palmitoylating enzyme. Indeed, modifying DHHC7 expression by specific silencing or overexpression, respectively, reduces or enhances Fas palmitoylation and DHHC7 co-immunoprecipitates with Fas. At a functional level, DHHC7-mediated palmitoylation of Fas allows a proper Fas expression level by preventing its degradation through the lysosomes. Indeed, the decrease of Fas expression obtained upon loss of Fas palmitoylation can be restored by inhibiting the lysosomal degradation pathway. We describe the modification of Fas by palmitoylation as a novel mechanism for the regulation of Fas expression through its ability to circumvent its degradation by lysosomal proteolysis. PMID:25301068

Cloning and expression of a novel lysophospholipase which structurally resembles lecithin cholesterol acyltransferase.

PubMed

Taniyama, Y; Shibata, S; Kita, S; Horikoshi, K; Fuse, H; Shirafuji, H; Sumino, Y; Fujino, M

1999-04-02

Lecithin cholesterol acyltransferase (LCAT) is the key enzyme in the esterification of plasma cholesterol and in the reverse cholesterol transport on high-density lipoprotein (HDL). We have found a novel LCAT-related gene among differentially expressed cDNA fragments between two types of foam cells derived from THP-1 cells, which are different in cholesterol efflux ability, using a subtractive PCR technique. The deduced 412-amino-acid sequence has 49% amino acid sequence similarity with human LCAT. In contrast to the liver-specific expression of LCAT, mRNA expression of the gene was observed mainly in peripheral tissues including kidney, placenta, pancreas, testis, spleen, heart, and skeletal muscle. The protein exists in human plasma and is probably associated with HDL. Moreover, we discovered that the recombinant protein hydrolyzed lysophosphatidylcholine (lysoPC), a proatherogenic lipid, to glycerophosphorylcholine and a free fatty acid. We have therefore named this novel enzyme LCAT-like lysophospholipase (LLPL), through which a new catabolic pathway for lysoPC on lipoproteins could be elucidated. Copyright 1999 Academic Press.

Discovery and characterization of inhibitors of human palmitoyl acyltransferases.

PubMed

Ducker, Charles E; Griffel, Lindsay K; Smith, Ryan A; Keller, Staci N; Zhuang, Yan; Xia, Zuping; Diller, John D; Smith, Charles D

2006-07-01

The covalent attachment of palmitate to specific proteins by the action of palmitoyl acyltransferases (PAT) plays critical roles in the biological activities of several oncoproteins. Two PAT activities are expressed by human cells: type 1 PATs that modify the farnesyl-dependent palmitoylation motif found in H- and N-Ras, and type 2 PATs that modify the myristoyl-dependent palmitoylation motif found in the Src family of tyrosine kinases. We have previously shown that the type 1 PAT HIP14 causes cellular transformation. In the current study, we show that mRNA encoding HIP14 is up-regulated in a number of types of human tumors. To assess the potential of HIP14 and other PATs as targets for new anticancer drugs, we developed three cell-based assays suitable for high-throughput screening to identify inhibitors of these enzymes. Using these screens, five chemotypes, with activity toward either type 1 or type 2 PAT activity, were identified. The activity of the hits were confirmed using assays that quantify the in vitro inhibition of PAT activity, as well as a cell-based assay that determines the abilities of the compounds to prevent the localization of palmitoylated green fluorescent proteins to the plasma membrane. Representative compounds from each chemotype showed broad antiproliferative activity toward a panel of human tumor cell lines and inhibited the growth of tumors in vivo. Together, these data show that PATs, and HIP14 in particular, are interesting new targets for anticancer compounds, and that small molecules with such activity can be identified by high-throughput screening.

Discovery and characterization of inhibitors of human palmitoyl acyltransferases

PubMed Central

Ducker, Charles E.; Griffel, Lindsay K.; Smith, Ryan A.; Keller, Staci N.; Zhuang, Yan; Xia, Zuping; Diller, John D.; Smith, Charles D.

2010-01-01

The covalent attachment of palmitate to specific proteins by the action of palmitoyl acyltransferases (PAT) plays critical roles in the biological activities of several oncoproteins. Two PAT activities are expressed by human cells: type 1 PATs that modify the farnesyl-dependent palmitoylation motif found in H- and N-Ras, and type 2 PATs that modify the myristoyl-dependent palmitoylation motif found in the Src family of tyrosine kinases. We have previously shown that the type 1 PAT HIP14 causes cellular transformation. In the current study, we show that mRNA encoding HIP14 is up-regulated in a number of types of human tumors. To assess the potential of HIP14 and other PATs as targets for new anticancer drugs, we developed three cell-based assays suitable for high-throughput screening to identify inhibitors of these enzymes. Using these screens, five chemotypes, with activity toward either type 1 or type 2 PAT activity, were identified. The activity of the hits were confirmed using assays that quantify the in vitro inhibition of PAT activity, as well as a cell-based assay that determines the abilities of the compounds to prevent the localization of palmitoylated green fluorescent proteins to the plasma membrane. Representative compounds from each chemotype showed broad antiproliferative activity toward a panel of human tumor cell lines and inhibited the growth of tumors in vivo. Together, these data show that PATs, and HIP14 in particular, are interesting new targets for anticancer compounds, and that small molecules with such activity can be identified by high-throughput screening. PMID:16891450

Alcoholism and Alcohol Abuse

MedlinePlus

... their drinking causes distress and harm. It includes alcoholism and alcohol abuse. Alcoholism, or alcohol dependence, is a disease that causes ... the liver, brain, and other organs. Drinking during pregnancy can harm your baby. Alcohol also increases the ...

Molecular Characterization of the Elaeis guineensis Medium-Chain Fatty Acid Diacylglycerol Acyltransferase DGAT1-1 by Heterologous Expression in Yarrowia lipolytica.

PubMed

Aymé, Laure; Jolivet, Pascale; Nicaud, Jean-Marc; Chardot, Thierry

2015-01-01

Diacylglycerol acyltransferases (DGAT) are involved in the acylation of sn-1,2-diacylglycerol. Palm kernel oil, extracted from Elaeis guineensis (oil palm) seeds, has a high content of medium-chain fatty acids mainly lauric acid (C12:0). A putative E. guineensis diacylglycerol acyltransferase gene (EgDGAT1-1) is expressed at the onset of lauric acid accumulation in the seed endosperm suggesting that it is a determinant of medium-chain triacylglycerol storage. To test this hypothesis, we thoroughly characterized EgDGAT1-1 activity through functional complementation of a Yarrowia lipolytica mutant strain devoid of neutral lipids. EgDGAT1-1 expression is sufficient to restore triacylglycerol accumulation in neosynthesized lipid droplets. A comparative functional study with Arabidopsis thaliana DGAT1 highlighted contrasting substrate specificities when the recombinant yeast was cultured in lauric acid supplemented medium. The EgDGAT1-1 expressing strain preferentially accumulated medium-chain triacylglycerols whereas AtDGAT1 expression induced long-chain triacylglycerol storage in Y. lipolytica. EgDGAT1-1 localized to the endoplasmic reticulum where TAG biosynthesis takes place. Reestablishing neutral lipid accumulation in the Y. lipolytica mutant strain did not induce major reorganization of the yeast microsomal proteome. Overall, our findings demonstrate that EgDGAT1-1 is an endoplasmic reticulum DGAT with preference for medium-chain fatty acid substrates, in line with its physiological role in palm kernel. The characterized EgDGAT1-1 could be used to promote medium-chain triacylglycerol accumulation in microbial-produced oil for industrial chemicals and cosmetics.

Molecular Characterization of the Elaeis guineensis Medium-Chain Fatty Acid Diacylglycerol Acyltransferase DGAT1-1 by Heterologous Expression in Yarrowia lipolytica

PubMed Central

Aymé, Laure; Jolivet, Pascale; Nicaud, Jean-Marc; Chardot, Thierry

2015-01-01

Diacylglycerol acyltransferases (DGAT) are involved in the acylation of sn-1,2-diacylglycerol. Palm kernel oil, extracted from Elaeis guineensis (oil palm) seeds, has a high content of medium-chain fatty acids mainly lauric acid (C12:0). A putative E. guineensis diacylglycerol acyltransferase gene (EgDGAT1-1) is expressed at the onset of lauric acid accumulation in the seed endosperm suggesting that it is a determinant of medium-chain triacylglycerol storage. To test this hypothesis, we thoroughly characterized EgDGAT1-1 activity through functional complementation of a Yarrowia lipolytica mutant strain devoid of neutral lipids. EgDGAT1-1 expression is sufficient to restore triacylglycerol accumulation in neosynthesized lipid droplets. A comparative functional study with Arabidopsis thaliana DGAT1 highlighted contrasting substrate specificities when the recombinant yeast was cultured in lauric acid supplemented medium. The EgDGAT1-1 expressing strain preferentially accumulated medium-chain triacylglycerols whereas AtDGAT1 expression induced long-chain triacylglycerol storage in Y. lipolytica. EgDGAT1-1 localized to the endoplasmic reticulum where TAG biosynthesis takes place. Reestablishing neutral lipid accumulation in the Y. lipolytica mutant strain did not induce major reorganization of the yeast microsomal proteome. Overall, our findings demonstrate that EgDGAT1-1 is an endoplasmic reticulum DGAT with preference for medium-chain fatty acid substrates, in line with its physiological role in palm kernel. The characterized EgDGAT1-1 could be used to promote medium-chain triacylglycerol accumulation in microbial-produced oil for industrial chemicals and cosmetics. PMID:26581109

Identification of a pair of phospholipid:diacylglycerol acyltransferases from developing flax (Linum usitatissimum L.) seed catalyzing the selective production of trilinolenin.

PubMed

Pan, Xue; Siloto, Rodrigo M P; Wickramarathna, Aruna D; Mietkiewska, Elzbieta; Weselake, Randall J

2013-08-16

The oil from flax (Linum usitatissimum L.) has high amounts of α-linolenic acid (ALA; 18:3(cis)(Δ9,12,15)) and is one of the richest sources of omega-3 polyunsaturated fatty acids (ω-3-PUFAs). To produce ∼57% ALA in triacylglycerol (TAG), it is likely that flax contains enzymes that can efficiently transfer ALA to TAG. To test this hypothesis, we conducted a systematic characterization of TAG-synthesizing enzymes from flax. We identified several genes encoding acyl-CoA:diacylglycerol acyltransferases (DGATs) and phospholipid:diacylglycerol acyltransferases (PDATs) from the flax genome database. Due to recent genome duplication, duplicated gene pairs have been identified for all genes except DGAT2-2. Analysis of gene expression indicated that two DGAT1, two DGAT2, and four PDAT genes were preferentially expressed in flax embryos. Yeast functional analysis showed that DGAT1, DGAT2, and two PDAT enzymes restored TAG synthesis when produced recombinantly in yeast H1246 strain. The activity of particular PDAT enzymes (LuPDAT1 and LuPDAT2) was stimulated by the presence of ALA. Further seed-specific expression of flax genes in Arabidopsis thaliana indicated that DGAT1, PDAT1, and PDAT2 had significant effects on seed oil phenotype. Overall, this study indicated the existence of unique PDAT enzymes from flax that are able to preferentially catalyze the synthesis of TAG containing ALA acyl moieties. The identified LuPDATs may have practical applications for increasing the accumulation of ALA and other polyunsaturated fatty acids in oilseeds for food and industrial applications.

Identification of a Pair of Phospholipid:Diacylglycerol Acyltransferases from Developing Flax (Linum usitatissimum L.) Seed Catalyzing the Selective Production of Trilinolenin*

PubMed Central

Pan, Xue; Siloto, Rodrigo M. P.; Wickramarathna, Aruna D.; Mietkiewska, Elzbieta; Weselake, Randall J.

2013-01-01

The oil from flax (Linum usitatissimum L.) has high amounts of α-linolenic acid (ALA; 18:3cisΔ9,12,15) and is one of the richest sources of omega-3 polyunsaturated fatty acids (ω-3-PUFAs). To produce ∼57% ALA in triacylglycerol (TAG), it is likely that flax contains enzymes that can efficiently transfer ALA to TAG. To test this hypothesis, we conducted a systematic characterization of TAG-synthesizing enzymes from flax. We identified several genes encoding acyl-CoA:diacylglycerol acyltransferases (DGATs) and phospholipid:diacylglycerol acyltransferases (PDATs) from the flax genome database. Due to recent genome duplication, duplicated gene pairs have been identified for all genes except DGAT2-2. Analysis of gene expression indicated that two DGAT1, two DGAT2, and four PDAT genes were preferentially expressed in flax embryos. Yeast functional analysis showed that DGAT1, DGAT2, and two PDAT enzymes restored TAG synthesis when produced recombinantly in yeast H1246 strain. The activity of particular PDAT enzymes (LuPDAT1 and LuPDAT2) was stimulated by the presence of ALA. Further seed-specific expression of flax genes in Arabidopsis thaliana indicated that DGAT1, PDAT1, and PDAT2 had significant effects on seed oil phenotype. Overall, this study indicated the existence of unique PDAT enzymes from flax that are able to preferentially catalyze the synthesis of TAG containing ALA acyl moieties. The identified LuPDATs may have practical applications for increasing the accumulation of ALA and other polyunsaturated fatty acids in oilseeds for food and industrial applications. PMID:23824186

Dual Role for Phospholipid:Diacylglycerol Acyltransferase: Enhancing Fatty Acid Synthesis and Diverting Fatty Acids from Membrane Lipids to Triacylglycerol in Arabidopsis Leaves[C][W

PubMed Central

Fan, Jilian; Yan, Chengshi; Zhang, Xuebin; Xu, Changcheng

2013-01-01

There is growing interest in engineering green biomass to expand the production of plant oils as feed and biofuels. Here, we show that PHOSPHOLIPID:DIACYLGLYCEROL ACYLTRANSFERASE1 (PDAT1) is a critical enzyme involved in triacylglycerol (TAG) synthesis in leaves. Overexpression of PDAT1 increases leaf TAG accumulation, leading to oil droplet overexpansion through fusion. Ectopic expression of oleosin promotes the clustering of small oil droplets. Coexpression of PDAT1 with oleosin boosts leaf TAG content by up to 6.4% of the dry weight without affecting membrane lipid composition and plant growth. PDAT1 overexpression stimulates fatty acid synthesis (FAS) and increases fatty acid flux toward the prokaryotic glycerolipid pathway. In the trigalactosyldiacylglycerol1-1 mutant, which is defective in eukaryotic thylakoid lipid synthesis, the combined overexpression of PDAT1 with oleosin increases leaf TAG content to 8.6% of the dry weight and total leaf lipid by fourfold. In the plastidic glycerol-3-phosphate acyltransferase1 mutant, which is defective in the prokaryotic glycerolipid pathway, PDAT1 overexpression enhances TAG content at the expense of thylakoid membrane lipids, leading to defects in chloroplast division and thylakoid biogenesis. Collectively, these results reveal a dual role for PDAT1 in enhancing fatty acid and TAG synthesis in leaves and suggest that increasing FAS is the key to engineering high levels of TAG accumulation in green biomass. PMID:24076979

Liver-specific inhibition of acyl-coenzyme a:cholesterol acyltransferase 2 with antisense oligonucleotides limits atherosclerosis development in apolipoprotein B100-only low-density lipoprotein receptor-/- mice.

PubMed

Bell, Thomas A; Brown, J Mark; Graham, Mark J; Lemonidis, Kristina M; Crooke, Rosanne M; Rudel, Lawrence L

2006-08-01

The purpose of this study was to determine the effects of liver-specific inhibition of acyl-coenzyme A:cholesterol acyltransferase 2 (ACAT2) on the development of hypercholesterolemia and atherosclerosis in mice. Apolipoprotein B100-only low-density lipoprotein (LDL) receptor-/- mice were given saline, a nontargeting control antisense oligonucleotide (ASO), or ASOs targeting ACAT2 biweekly for a period spanning 16 weeks. Mice treated with ACAT2 targeting ASOs had liver-specific reduction in ACAT2 mRNA, yet intestinal ACAT2 and cholesterol absorption was left undisturbed. ASO-mediated knockdown of ACAT2 resulted in reduction of total plasma cholesterol, increased levels of plasma triglyceride, and a shift in LDL cholesteryl ester (CE) fatty acid composition from mainly saturated and monounsaturated to polyunsaturated fatty acid enrichment. Furthermore, the liver-specific depletion of ACAT2 resulted in protection against diet-induced hypercholesterolemia and aortic CE deposition. This is the first demonstration that specific pharmacological inhibition of ACAT2, without affecting ACAT1, is atheroprotective. Hepatic ACAT2 plays a critical role in driving the production of atherogenic lipoproteins, and therapeutic interventions, such as the ACAT2-specific ASOs used here, which reduce acyltransferase 2 (ACAT2) function in the liver without affecting ACAT1, may provide clinical benefit for cardiovascular disease prevention.

Discovery of Tetralones as Potent and Selective Inhibitors of Acyl-CoA:Diacylglycerol Acyltransferase 1.

PubMed

Cheung, Mui; Tangirala, Raghuram S; Bethi, Sridhar R; Joshi, Hemant V; Ariazi, Jennifer L; Tirunagaru, Vijaya G; Kumar, Sanjay

2018-02-08

Acyl-CoA:diacylglycerol acyltransferase 1 (DGAT1) plays an important role in triglyceride synthesis and is a target of interest for the treatment of metabolic disorders. Herein we describe the structure-activity relationship of a novel tetralone series of DGAT1 inhibitors and our strategies for overcoming genotoxic liability of the anilines embedded in the chemical structures, leading to the discovery of a candidate compound, ( S )-2-(6-(5-(3-(3,4-difluorophenyl)ureido)pyrazin-2-yl)-1-oxo-2-(2,2,2-trifluoroethyl)-1,2,3,4-tetrahydronaphthalen-2-yl)acetic acid (GSK2973980A, 26d ). Compound 26d is a potent and selective DGAT1 inhibitor with excellent DMPK profiles and in vivo efficacy in a postprandial lipid excursion model in mice. Based on the overall biological and developability profiles and acceptable safety profiles in the 7-day toxicity studies in rats and dogs, compound 26d was selected as a candidate compound for further development in the treatment of metabolic disorders.

The Role of Diacylglycerol Acyltransferase (DGAT) 1 and 2 in Cardiac Metabolism and Function.

PubMed

Roe, Nathan D; Handzlik, Michal K; Li, Tao; Tian, Rong

2018-03-21

It is increasingly recognized that synthesis and turnover of cardiac triglyceride (TG) play a pivotal role in the regulation of lipid metabolism and function of the heart. The last step in TG synthesis is catalyzed by diacylglycerol:acyltransferase (DGAT) which esterifies the diacylglycerol with a fatty acid. Mammalian heart has two DGAT isoforms, DGAT1 and DGAT2, yet their roles in cardiac metabolism and function remain poorly defined. Here, we show that inactivation of DGAT1 or DGAT2 in adult mouse heart results in a moderate suppression of TG synthesis and turnover. Partial inhibition of DGAT activity increases cardiac fatty acid oxidation without affecting PPARα signaling, myocardial energetics or contractile function. Moreover, coinhibition of DGAT1/2 in the heart abrogates TG turnover and protects the heart against high fat diet-induced lipid accumulation with no adverse effects on basal or dobutamine-stimulated cardiac function. Thus, the two DGAT isoforms in the heart have partially redundant function, and pharmacological inhibition of one DGAT isoform is well tolerated in adult hearts.

Identification of the catalytic triad of the lipase/acyltransferase from Aeromonas hydrophila.

PubMed Central

Brumlik, M J; Buckley, J T

1996-01-01

Aeromonas hydrophila secretes a lipolytic enzyme that has several properties in common with the mammalian enzyme lecithin-cholesterol acyltransferase. We have recently shown that it is a member of a newly described group of proteins that contain five similar blocks of sequence arranged in the same order in their primary structures (C. Upton and J. T. Buckley, Trends Biochem. Sci. 233:178-179, 1995). Assuming that, like other lipases, these enzymes have a Ser-Asp-His catalytic triad, we used these blocks to predict which aspartic acid and histidine would be at the active site of the Aeromonas enzyme. Targeted residues were replaced with other amino acids by site-directed mutagenesis, and the effects on secretion and activity were assessed. Changing His-291 to asparagine completely abolished enzyme activity, although secretion by the bacteria was not affected. Only very small amounts of the D116N mutant appeared in the culture supernatant, likely because it is sensitive to periplasmic proteases it encounters en route. Assays of crude preparations containing this variant showed no detectable enzyme activity. We conclude that, together with Ser-16, which we have identified previously, Asp-116 and His-291 compose the catalytic triad of the enzyme. PMID:8606184

Alcohol use by alcoholics with and without a history of parental alcoholism.

PubMed

Worobec, T G; Turner, W M; O'Farrell, T J; Cutter, H S; Bayog, R D; Tsuang, M T

1990-12-01

The association between parental history of alcoholism and the nature of alcoholism was assessed using a more reliable measure of family history (Family Tree Questionnaire) and a more comprehensive inventory of alcoholism (Alcohol Use Inventory) than used in earlier studies. Parental alcoholism was associated with more severe alcoholism on most parameters of alcohol use (age of onset, quantity, frequency, preoccupation, and sustained use) and alcohol-related problems (social, vocational, physical, cognitive, and loss of control). The association between parental history of alcoholism and more severe alcoholism in the probands was independent of age of onset of alcoholism, current age, socioeconomic background, and marital status. Parental history positive (PH+) alcoholics were more reliant on alcohol to manage their moods but did not differ significantly from parental history negative (PH-) alcoholics in the use of alcohol to improve sociability or mental functioning or to cope with marital problems. Surprisingly, the degree of concern, guilt, and worry over the negative consequences of drinking was not significantly different for PH+ alcoholics although the negative consequences were clearly much more severe for this group. While the data are inconclusive about the reasons for more severe alcoholism in PH+ alcoholics, greater reliance on ethanol to manage moods and a relative insensitivity to negative consequences could theoretically account for the vulnerability to more severe alcoholism found in PH+ alcoholics.

Characterization of the Plasmodium falciparum and P. berghei glycerol 3-phosphate acyltransferase involved in FASII fatty acid utilization in the malaria parasite apicoplast.

PubMed

Shears, Melanie J; MacRae, James I; Mollard, Vanessa; Goodman, Christopher D; Sturm, Angelika; Orchard, Lindsey M; Llinás, Manuel; McConville, Malcolm J; Botté, Cyrille Y; McFadden, Geoffrey I

2017-01-01

Malaria parasites can synthesize fatty acids via a type II fatty acid synthesis (FASII) pathway located in their apicoplast. The FASII pathway has been pursued as an anti-malarial drug target, but surprisingly little is known about its role in lipid metabolism. Here we characterize the apicoplast glycerol 3-phosphate acyltransferase that acts immediately downstream of FASII in human (Plasmodium falciparum) and rodent (Plasmodium berghei) malaria parasites and investigate how this enzyme contributes to incorporating FASII fatty acids into precursors for membrane lipid synthesis. Apicoplast targeting of the P. falciparum and P. berghei enzymes are confirmed by fusion of the N-terminal targeting sequence to GFP and 3' tagging of the full length protein. Activity of the P. falciparum enzyme is demonstrated by complementation in mutant bacteria, and critical residues in the putative active site identified by site-directed mutagenesis. Genetic disruption of the P. falciparum enzyme demonstrates it is dispensable in blood stage parasites, even in conditions known to induce FASII activity. Disruption of the P. berghei enzyme demonstrates it is dispensable in blood and mosquito stage parasites, and only essential for development in the late liver stage, consistent with the requirement for FASII in rodent malaria models. However, the P. berghei mutant liver stage phenotype is found to only partially phenocopy loss of FASII, suggesting newly made fatty acids can take multiple pathways out of the apicoplast and so giving new insight into the role of FASII and apicoplast glycerol 3-phosphate acyltransferase in malaria parasites. © 2016 The Authors Cellular Microbiology Published by John Wiley & Sons Ltd.

Detection of erythrocyte membrane structural abnormalities in lecithin: cholesterol acyltransferase deficiency using a spin label approach.

PubMed

Maraviglia, B; Herring, F G; Weeks, G; Godin, D V

1979-01-01

The membrane fluidity of erythrocytes from patients with Lecithin: cholesterol acyltransferase (LCAT) deficiency was studied by means of electron spin resonance. The temperature dependence of the separation of the outer extrema of the spectra of 2-(3-carboxy-propyl)-4,4-dimethyl, 2-tridecyl-3-oxazolidinyloxyl spin probe was monitored for normal, presumed carrier and clinically affected subjects. The temperature profile of controls was significantly different from that of the presumed carriers and the clinically affected individuals. The results show that the compositional abnormalities previously noted in erythrocyte membranes from patients with LCAT deficiency are associated with alterations in the physiocochemical state of the membrane. An investigation of the spectral lineshapes below 10 degrees C allowed a distinction to be made at the membrane level between clinically affected subjects and clinically normal heterozygous carriers. Alterations in the temperature dependence of elec-ron spin resonance parameters may provide a sensitive index of red cell membrane alterations in pathological states of generalized membrane involvement.

Genome-Wide Identification of BAHD Acyltransferases and In vivo Characterization of HQT-like Enzymes Involved in Caffeoylquinic Acid Synthesis in Globe Artichoke

PubMed Central

Moglia, Andrea; Acquadro, Alberto; Eljounaidi, Kaouthar; Milani, Anna M.; Cagliero, Cecilia; Rubiolo, Patrizia; Genre, Andrea; Cankar, Katarina; Beekwilder, Jules; Comino, Cinzia

2016-01-01

Globe artichoke (Cynara cardunculus L. var. scolymus) is a rich source of compounds promoting human health (phytonutrients), among them caffeoylquinic acids (CQAs), mainly represented by chlorogenic acid (CGA), and dicaffeoylquinic acids (diCQAs). The enzymes involved in their biosynthesis belong to the large family of BAHD acyltransferases. Following a survey of the globe artichoke genome, we identified 69 BAHD proteins carrying the catalytic site (HXXXD). Their phylogenetic analysis together with another 43 proteins, from 21 species, representative of the BAHD family, highlighted their grouping in seven major clades. Nine globe artichoke acyltransferases clustered in a sub-group of Clade V, with 3 belonging to hydroxycinnamoyl-CoA:quinate hydroxycinnamoyl transferase (HQT) and 2 to hydroxycinnamoyl-CoA:shikimate/quinate hydroxycinnamoyl transferase (HCT) like proteins. We focused our attention on the former, HQT1, HQT2, and HQT3, as they are known to play a key role in CGA biosynthesis. The expression of genes coding for the three HQTs and correlation of expression with the CQA content is reported for different globe artichoke tissues. For the first time in the globe artichoke, we developed and applied the virus-induced gene silencing approach with the goal of assessing in vivo the effect of HQT1 silencing, which resulted in a marked reduction of both CGA and diCQAs. On the other hand, when the role of the three HQTs was assessed in leaves of Nicotiana benthamiana through their transient overexpression, significant increases in mono- and diCQAs content were observed. Using transient GFP fusion proteins expressed in N. benthamiana leaves we also established the sub-cellular localization of these three enzymes. PMID:27721818

The Arabidopsis DCR Encoding a Soluble BAHD Acyltransferase Is Required for Cutin Polyester Formation and Seed Hydration Properties1[C][W][OA

PubMed Central

Panikashvili, David; Shi, Jian Xin; Schreiber, Lukas; Aharoni, Asaph

2009-01-01

The cuticle covering every plant aerial organ is largely made of cutin that consists of fatty acids, glycerol, and aromatic monomers. Despite the huge importance of the cuticle to plant development and fitness, our knowledge regarding the assembly of the cutin polymer and its integration in the complete cuticle structure is limited. Cutin composition implies the action of acyltransferase-type enzymes that mediate polymer construction through ester bond formation. Here, we show that a member of the BAHD family of acyltransferases (DEFECTIVE IN CUTICULAR RIDGES [DCR]) is required for incorporation of the most abundant monomer into the polymeric structure of the Arabidopsis (Arabidopsis thaliana) flower cutin. DCR-deficient plants display phenotypes that are typically associated with a defective cuticle, including altered epidermal cell differentiation and postgenital organ fusion. Moreover, levels of the major cutin monomer in flowers, 9(10),16-dihydroxy-hexadecanoic acid, decreased to an almost undetectable amount in the mutants. Interestingly, dcr mutants exhibit changes in the decoration of petal conical cells and mucilage extrusion in the seed coat, both phenotypes formerly not associated with cutin polymer assembly. Excessive root branching displayed by dcr mutants and the DCR expression pattern in roots pointed to the function of DCR belowground, in shaping root architecture by influencing lateral root emergence and growth. In addition, the dcr mutants were more susceptible to salinity, osmotic, and water deprivation stress conditions. Finally, the analysis of DCR protein localization suggested that cutin polymerization, possibly the oligomerization step, is partially carried out in the cytoplasmic space. Therefore, this study extends our knowledge regarding the functionality of the cuticular layer and the formation of its major constituent the polymer cutin. PMID:19828672

[Out of addictions: Alcohol, or alcohol to alcohol].

PubMed

Simmat-Durand, L; Vellut, N; Lejeune, C; Jauffret-Roustide, M; Mougel, S; Michel, L; Planche, M

2017-08-01

Pathways from alcoholism to recovery are documented; less often are those from drug addiction to alcoholism. Biographical approaches allow analyzing how people change their uses and talk about their trajectories of recovery. Three hundred and forty-one people (34% women) in the Paris area were questioned on their trajectories with a biographical questionnaire. Some open questions were aimed to understand the connection they made between events in their lives, how recovered they felt and what they considered strengths or obstacles. All the participants had stopped at least one product. Their mean age was 43, and 26% were over 50. How can the differences between one substance addicts and dual abusers be explained? Can we hypothesize a better result for the patients with a single dependence to alcohol in their lives for the following two reasons? (1) They could really be taken in charge for their alcoholism whereas the dual abusers mostly receive cared for their illicit drug problems with an under estimation of their problem with alcohol. In this case, they turn to alcohol after weaning themselves from their drug dependence so as to return to a social consumption, especially when they are given an opiate treatment. (2) Conversely could we suggest that the dual substance abusers had different trajectories from their childhood (more adverse events, more social difficulties, mental health problems), and that this accumulation explains their skipping from one substance or behaviour to another without any real recovery for decades? All respondents were polydrug users. Eighty-two had been dependent mainly on alcohol. One hundred and twenty-one people had been drug addicts (mostly heroin), which they had stopped on average ten years before the survey. The last group included 138 persons who had been heroin or cocaine addicts and alcoholics in their lives, a third of whom had been dependent on alcohol before their drug addiction (35%), a tenth on both at the same time (10

Map-based cloning and characterization of Zea mays male sterility33 (ZmMs33) gene, encoding a glycerol-3-phosphate acyltransferase.

PubMed

Xie, Ke; Wu, Suowei; Li, Ziwen; Zhou, Yan; Zhang, Danfeng; Dong, Zhenying; An, Xueli; Zhu, Taotao; Zhang, Simiao; Liu, Shuangshuang; Li, Jinping; Wan, Xiangyuan

2018-06-01

Map-based cloning of maize ms33 gene showed that ZmMs33 encodes a sn-2 glycerol-3-phosphate acyltransferase, the ortholog of rice OsGPAT3, and it is essential for male fertility in maize. Genetic male sterility has been widely studied for its biological significance and commercial value in hybrid seed production. Although many male-sterile mutants have been identified in maize (Zea mays L.), it is likely that most genes that cause male sterility are unknown. Here, we report a recessive genetic male-sterile mutant, male sterility33 (ms33), which displays small, pale yellow anthers, and complete male sterility. Using a map-based cloning approach, maize GRMZM2G070304 was identified as the ms33 gene (ZmMs33). ZmMs33 encodes a novel sn-2 glycerol-3-phosphate acyltransferase (GPAT) in maize. A functional complementation experiment showed that GRMZM2G070304 can rescue the male-sterile phenotype of the ms33-6029 mutant. GRMZM2G070304 was further confirmed to be the ms33 gene via targeted knockouts induced by the clustered regularly interspersed short palindromic repeats (CRISPR)/Cas9 system. ZmMs33 is preferentially expressed in the immature anther from the quartet to early-vacuolate microspore stages and in root tissues at the fifth leaf growth stage. Phylogenetic analysis indicated that ZmMs33 and OsGPAT3 are evolutionarily conserved for anther and pollen development in monocot species. This study reveals that the monocot-specific GPAT3 protein plays an important role in male fertility in maize, and ZmMs33 and mutants in this gene may have value in maize male-sterile line breeding and hybrid seed production.

Essential oil of Pinus koraiensis leaves exerts antihyperlipidemic effects via up-regulation of low-density lipoprotein receptor and inhibition of acyl-coenzyme A: cholesterol acyltransferase.

PubMed

Kim, Ji-Hyun; Lee, Hyo-Jung; Jeong, Soo-Jin; Lee, Min-Ho; Kim, Sung-Hoon

2012-09-01

Hyperlipidemia is an important factor to induce metabolic syndrome such as obesity, diabetes and cardiovascular diseases. Recently, some antihyperlipidemic agents from herbal medicines have been in the spotlight in the medical science field. Thus, the present study evaluated the antihyperlipidemic activities of the essential oil from the leaves of Pinus koraiensis SIEB (EOPK) that has been used as a folk remedy for heart disease. The reverse transcription polymerase chain reaction (RT-PCR) revealed that EOPK up-regulated low density lipoprotein receptor (LDLR) at the mRNA level as well as negatively suppressed the expression of sterol regulatory element-binding protein (SREBP)-1c, SREBP-2, 3-hydroxy-3-methyl-glutaryl-CoA reductase (HMGCR), fatty acid synthase (FAS) and glycerol-3-phosphate acyltransferase (GPAT) involved in lipid metabolism in HepG2 cells. Also, western blotting showed that EOPK activated LDLR and attenuated the expression of FAS at the protein level in the cells. Consistently, EOPK significantly inhibited the level of human acylcoenzyme A: cholesterol acyltransferase (hACAT)1 and 2 and reduced the low-density lipoprotein (LDL) oxidation activity. Furthermore, chromatography-mass spectrometry (GC-MS) analysis showed that EOPK, an essential oil mixture, contained camphene (21.11%), d-limonene (21.01%), α-pinene (16.74%) and borneol (11.52%). Overall, the findings suggest that EOPK can be a potent pharmaceutical agent for the prevention and treatment of hyperlipidemia. Copyright © 2012 John Wiley & Sons, Ltd.

Genetic variants in PNPLA3 and TM6SF2 predispose to the development of hepatocellular carcinoma in individuals with alcohol-related cirrhosis.

PubMed

Stickel, Felix; Buch, Stephan; Nischalke, Hans Dieter; Weiss, Karl Heinz; Gotthardt, Daniel; Fischer, Janett; Rosendahl, Jonas; Deltenre, Pierre; Marot, Astrid; Elamly, Mona; Casper, Markus; Lammert, Frank; McQuillin, Andrew; Zopf, Steffen; Spengler, Ulrich; Marhenke, Silke; Kirstein, Martha M; Vogel, Arndt; Eyer, Florian; von Felden, Johann; Wege, Henning; Buch, Thorsten; Schafmayer, Clemens; Braun, Felix; Berg, Thomas; Morgan, Marsha Y; Hampe, Jochen

2018-03-13

Variants in patatin-like phospholipase domain-containing 3 (PNPLA3; rs738409), transmembrane 6 superfamily member 2 (TM6SF2; rs58542926), and membrane bound O-acyltransferase domain containing 7 (MBOAT7; rs641738) are risk factors for the development of alcohol-related cirrhosis. Within this population, PNPLA3 rs738409 is also an established risk factor for the development of hepatocellular carcinoma (HCC). The aim of this study was to explore possible risk associations of TM6SF2 rs58542926 and MBOAT7 rs641738 with HCC. Risk variants in PNPLA3, TM6SF2, and MBOAT7 were genotyped in 751 cases with alcohol-related cirrhosis and HCC and in 1165 controls with alcohol-related cirrhosis without HCC. Association with the risk of developing HCC was analyzed using multivariate logistic regression. The development of HCC was independently associated with PNPLA3 rs738409 (OR adjusted 1.84 [95% CI 1.55-2.18], p = 1.85 × 10 -12 ) and TM6SF2 rs58542926 (OR adjusted 1.66 [1.30-2.13], p = 5.13 × 10 -05 ), using an additive model, and controlling the sex, age, body mass index, and type 2 diabetes mellitus; the risk associated with carriage of MBOAT7 rs641738 (OR adjusted 1.04 [0.88-1.24], p = 0.61) was not significant. The population-attributable fractions were 43.5% for PNPLA3 rs738409, 11.5% for TM6SF2 rs58542926, and 49.9% for the carriage of both the variants combined. Carriage of TM6SF2 rs58542926 is an additional risk factor for the development of HCC in people with alcohol-related cirrhosis. Carriage of both PNPLA3 rs738409 and TM6SF2 rs58542926 accounts for half of the attributable risk for HCC in this population. Genotyping will allow for more precise HCC risk-stratification of patients with alcohol-related cirrhosis, and genotype-guided screening algorithms would optimize patient care.

Hyperspectral Imaging and Spectroscopy of Fluorescently Coupled Acyl-CoA: Cholesterol Acyltransferase in Insect Cells

NASA Technical Reports Server (NTRS)

Malak, H.; Mahtani, H.; Herman, P.; Vecer, J.; Lu, X.; Chang, T. Y.; Richmond, Robert C.; Whitaker, Ann F. (Technical Monitor)

2001-01-01

A high-performance hyperspectral imaging module with high throughput of light suitable for low-intensity fluorescence microscopic imaging and subsequent analysis, including single-pixel-defined emission spectroscopy, was tested on Sf21 insect cells expressing green fluorescence associated with recombinant green fluorescent protein linked or not with the membrane protein acyl-CoA:cholesterol acyltransferase. The imager utilized the phenomenon of optical activity as a new technique providing information over a spectral range of 220-1400 nm, and was inserted between the microscope and an 8-bit CCD video-rate camera. The resulting fluorescence image did not introduce observable image aberrations. The images provided parallel acquisition of well resolved concurrent spatial and spectral information such that fluorescence associated with green fluorescent protein alone was demonstrated to be diffuse within the Sf21 insect cell, and that green fluorescence associated with the membrane protein was shown to be specifically concentrated within regions of the cell cytoplasm. Emission spectra analyzed from different regions of the fluorescence image showed blue shift specific for the regions of concentration associated with the membrane protein.

Aromatic amine metabolism: immunochemical relationships of N-acetyltransferase and N,O-acyltransferase

DOE Office of Scientific and Technical Information (OSTI.GOV)

Land, S.; Allaben, W.T.; King, C.M.

1986-05-01

Mutagenic and carcinogenic aromatic amines are acetylated in most organisms. Acetyl CoA and arylhydroxamic acids can serve as acetyl donors for N-Acetylation of amines to yield stable amides, or by O-acetylation of hydroxylamine derivatives to produce reactive metabolites that can react covalently with nucleic acid. Polyclonal antibodies against rat arylhydroxamic acid, N,O-acyltransferase (AHAT) have been compared for their abilities to react with this enzyme and the acetyl CoA-dependent N-acetyltransferase (NAT) of the rat, rabbit, hamster, mouse and human. Liver cytosols were treated with increasing quantities of antibodies from immune or control rabbits. Immune complexes were removed by treatment with proteinmore » A-Sepharose before assay of nucleic acid adduct formation by AHAT activation of N-hydroxy-2-acetylaminofluorene and the acetylation of 2-aminofluorene by NAT. Both rat activities, the AHAT of the hamster and the NAT of the mouse and human were removed by this treatment. No decrease in NAT activity of hamster, or of either rabbit cytosol activity was observed. Neither mouse nor human liver has appreciable AHAT activity. These data support the idea that AHAT and NAT of rat, AHAT of hamster and NAT of mouse and human liver are immunochemically related, but that NAT of the hamster is an immunochemically distinct peptide.« less

Apigenin protects against alcohol-induced liver injury in mice by regulating hepatic CYP2E1-mediated oxidative stress and PPARα-mediated lipogenic gene expression.

PubMed

Wang, Feng; Liu, Jin-Cheng; Zhou, Rui-Jun; Zhao, Xi; Liu, Mei; Ye, Hua; Xie, Mei-Lin

2017-09-25

Alcohol is a major cause of liver injury, and there are currently no ideal pharmacological reagents that can prevent or reverse this disease. Apigenin is one of the most common flavonoids present in numerous plants and has many beneficial effects. But whether or not apigenin may protect against alcohol-induced liver injury remains unknown. Our aim was to examine the effect and potential mechanisms. The experimental mice were given 56% erguotou wine or simultaneously given apigenin 150-300 mg/kg by gavage for 30 days. The results showed that in the apigenin-treated mice, the expression of hepatic cytochrome P450 2E1 (CYP2E1) and nuclear factor kappa B proteins as well as contents of hepatic malondialdehyde and tumor necrosis factor-alpha were reduced, while the levels of hepatic reduced glutathione, glutathione reductase, glutathione peroxidase, and glutathione S-transferase were increased, especially in the 300 mg/kg group. A significant change in hepatic steatosis was also observed in the apigenin 300 mg/kg group. Apigenin pretreatment could increase the expression of hepatic peroxisome proliferator-activated receptor alpha (PPARα) and carnitine palmitoyltransferase-1 proteins, and decrease the expression of hepatic sterol regulatory element binding protein-1c, fatty acid synthase, and diacylglycerol acyltransferase proteins. These findings demonstrated that apigenin might exert a protective effect on alcohol-induced liver injury, and its mechanisms might be related to the regulations of hepatic CYP2E1-mediated oxidative stress and PPARα-mediated lipogenic gene expression. Copyright © 2017 Elsevier B.V. All rights reserved.

The modules of trans-acyltransferase assembly lines redefined with a central acyl carrier protein.

PubMed

Vander Wood, Drew A; Keatinge-Clay, Adrian T

2018-06-01

Here, the term "module" is redefined for trans-acyltransferase (trans-AT) assembly lines to agree with how its domains cooperate and evolutionarily co-migrate. The key domain in both the polyketide synthase (PKS) and nonribosomal peptide synthetase (NRPS) modules of assembly lines is the acyl carrier protein (ACP). ACPs not only relay growing acyl chains through the assembly line but also collaborate with enzymes in modules, both in cis and in trans, to add a specific chemical moiety. A ketosynthase (KS) downstream of ACP often plays the role of gatekeeper, ensuring that only a single intermediate generated by the enzymes of a module is passed downstream. Bioinformatic analysis of 526 ACPs from 33 characterized trans-AT assembly lines reveals ACPs from the same module type generally clade together, reflective of the co-evolution of these domains with their cognate enzymes. While KSs downstream of ACPs from the same module type generally also clade together, KSs upstream of ACPs do not-in disagreement with the traditional definition of a module. Beyond nomenclature, the presented analysis impacts our understanding of module function, the evolution of assembly lines, pathway prediction, and assembly line engineering. © 2018 Wiley Periodicals, Inc.

Enzymatic production of L-alanyl-L-glutamine by recombinant E. coli expressing α-amino acid ester acyltransferase from Sphingobacterium siyangensis.

PubMed

Hirao, Yoshinori; Mihara, Yasuhiro; Kira, Ikuo; Abe, Isao; Yokozeki, Kenzo

2013-01-01

An enzymatic production method for synthesizing L-alanyl-L-glutamine (Ala-Gln) from L-alanine methyl ester hydrochloride (AlaOMe) and L-glutamine (Gln) was developed in this study. The cultivation conditions for an Escherichia coli strain overexpressing α-amino acid ester acyltransferase from Sphingobacterium siyangensis AJ 2458 (SAET) and reaction conditions for Ala-Gln production were optimized. A high cell density culture broth prepared by fed-batch cultivation showed 440 units/mL of Ala-Gln-producing activity. In addition, an Ala-Gln-producing reaction using intact E. coli cells overexpressing SAET under optimum conditions was conducted. A total Ala-Gln yield of 69.7 g/L was produced in 40 min. The molar yield was 67% against both AlaOMe and Gln.

Alcoholism and alcohol drinking habits predicted from alcohol dehydrogenase genes.

PubMed

Tolstrup, Janne Schurmann; Nordestgaard, Børge Grønne; Rasmussen, Søren; Tybjaerg-Hansen, Anne; Grønbaek, Morten

2008-06-01

Alcohol drinking habits and alcoholism are partly genetically determined. Alcohol is degraded primarily by alcohol dehydrogenase (ADH) wherein genetic variation that affects the rate of alcohol degradation is found in ADH1B and ADH1C. It is biologically plausible that these variations may be associated with alcohol drinking habits and alcoholism. By genotyping 9080 white men and women from the general population, we found that men and women with ADH1B slow vs fast alcohol degradation drank more alcohol and had a higher risk of everyday drinking, heavy drinking, excessive drinking and of alcoholism. For example, the weekly alcohol intake was 9.8 drinks (95% confidence interval (CI): 9.1-11) among men with the ADH1B.1/1 genotype compared to 7.5 drinks (95% CI: 6.4-8.7) among men with the ADH1B.1/2 genotype, and the odds ratio (OR) for heavy drinking was 3.1 (95% CI: 1.7-5.7) among men with the ADH1B.1/1 genotype compared to men with the ADH1B.1/2 genotype. Furthermore, individuals with ADH1C slow vs fast alcohol degradation had a higher risk of heavy and excessive drinking. For example, the OR for heavy drinking was 1.4 (95% CI: 1.1-1.8) among men with the ADH1C.1/2 genotype and 1.4 (95% CI: 1.0-1.9) among men with the ADH1B.2/2 genotype, compared with men with the ADH1C.1/1 genotype. Results for ADH1B and ADH1C genotypes among men and women were similar. Finally, because slow ADH1B alcohol degradation is found in more than 90% of the white population compared to less than 10% of East Asians, the population attributable risk of heavy drinking and alcoholism by ADH1B.1/1 genotype was 67 and 62% among the white population compared with 9 and 24% among the East Asian population.

The influence of alcohol-specific communication on adolescent alcohol use and alcohol-related consequences.

PubMed

Reimuller, Alison; Hussong, Andrea; Ennett, Susan T

2011-12-01

Alcohol-specific communication, a direct conversation between an adult and an adolescent regarding alcohol use, contains messages about alcohol relayed from the adult to the child. The current study examined the construct of alcohol-specific communication and the effect of messages on adolescent alcohol use and alcohol-related consequences. Parent-adolescent dyads were assessed biannually for 3 years (grades 9-11 at wave 6) to examine these relations in a large longitudinal study of adolescents initially in grades 6 through 8. An exploratory factor analysis identified two factors among alcohol-specific communication items, permissive messages and negative alcohol messages. Results showed previous level of adolescent alcohol use moderated the relation between permissive messages and alcohol use outcomes. Plotting of these interactions showed greater alcohol use and consequences with increasing permissive messages in adolescents with higher versus lower levels of previous alcohol use. Results suggest that parental messages regarding alcohol use may impact adolescent alcohol use beyond the effect of general parenting style and parental alcohol use.

The Influence of Alcohol-specific Communication on Adolescent Alcohol Use and Alcohol-related Consequences

PubMed Central

Reimuller, Alison; Hussong, Andrea; Ennett, Susan T.

2013-01-01

Alcohol-specific communication, a direct conversation between an adult and an adolescent regarding alcohol use, contains messages about alcohol relayed from the adult to the child. The current study examined the construct of alcohol-specific communication and the effect of messages on adolescent alcohol use and alcohol-related consequences. Parent-adolescent dyads were assessed biannually for 3 years (grades 9-11 at wave 6) to examine these relations in a large longitudinal study of adolescents initially in grades 6 through 8. An exploratory factor analysis identified two factors among alcohol-specific communication items, permissive messages and negative alcohol messages. Results showed previous level of adolescent alcohol use moderated the relation between permissive messages and alcohol use outcomes. Plotting of these interactions showed greater alcohol use and consequences with increasing permissive messages in adolescents with higher versus lower levels of previous alcohol use. Results suggest that parental messages regarding alcohol use may impact adolescent alcohol use beyond the effect of general parenting style and parental alcohol use. PMID:21667141

Alcoholics' selective attention to alcohol stimuli: automated processing?

PubMed

Stormark, K M; Laberg, J C; Nordby, H; Hugdahl, K

2000-01-01

This study investigated alcoholics' selective attention to alcohol words in a version of the Stroop color-naming task. Alcoholic subjects (n = 23) and nonalcoholic control subjects (n = 23) identified the color of Stroop versions of alcohol, emotional, neutral and color words. Manual reaction times (RTs), skin conductance responses (SCRs) and heart rate (HR) were recorded. Alcoholics showed overall longer RTs than controls while both groups were slower in responding to the incongruent color words than to the other words. Alcoholics showed longer RTs to both alcohol (1522.7 milliseconds [ms]) and emotional words (1523.7 ms) than to neutral words (1450.8 ms) which suggests that the content of these words interfered with the ability to attend to the color of the words. There was also a negative correlation (r = -.41) between RT and response accuracy to alcohol words for the alcoholics, reflecting that the longer time the alcoholics used to respond to the color of the alcohol words, the more incorrect their responses were. The alcoholics also showed significantly greater SCRs to alcohol words (0.16 microSiemens) than to any of the other words (ranging from 0.04-0.08 microSiemens), probably reflecting the emotional significance of the alcohol words. Finally, the alcoholics evidenced smaller HR acceleration to alcohol (1.9 delta bpm) compared to neutral (2.8 delta bpm), which could be related to difficulties alcoholics experience in terminating their attention to the alcohol words. These findings indicate that it is difficult for alcoholics to regulate their attention to alcohol stimuli, suggesting that alcoholics' processing of alcohol information is automated.

Marital Interaction in Alcoholic and Nonalcoholic Couples: Alcoholic Subtype Variations and Wives’ Alcoholism Status

PubMed Central

Floyd, Frank J.; Daugherty, Michelle Klotz; Fitzgerald, Hiram H.; Cranford, James A.; Zucker, Robert A.

2008-01-01

The authors examined problem-solving marital interactions of alcoholic and nonalcoholic couples (N = 132). Four alcoholic groups (husband alcoholic with antisocial personality disorder or not, paired with alcoholic or nonalcoholic wives) were compared with each other and with a both-spouses-nonalcoholic group. Consistent with the alcoholic subtypes hypothesis, couples with an antisocial alcoholic husband had higher levels of hostile behavior regardless of wives’ alcoholism status. In contrast, rates of positive behaviors and the ratio of positive to negative behaviors were greatest among couples in which either both or neither of the spouses had alcoholic diagnoses and were lowest among alcoholic husbands with nonalcoholic wives. Discussion focuses on possible mechanisms linking antisocial alcoholism and discrepant alcoholic diagnoses to poorer marital outcomes. PMID:16492103

Identification and characterization of an efficient acyl-CoA: diacylglycerol acyltransferase 1 (DGAT1) gene from the microalga Chlorella ellipsoidea.

PubMed

Guo, Xuejie; Fan, Chengming; Chen, Yuhong; Wang, Jingqiao; Yin, Weibo; Wang, Richard R C; Hu, Zanmin

2017-02-21

Oil in the form of triacylglycerols (TAGs) is quantitatively the most important storage form of energy for eukaryotic cells. Diacylglycerol acyltransferase (DGAT) is considered the rate-limiting enzyme for TAG accumulation. Chlorella, a unicellular eukaryotic green alga, has attracted much attention as a potential feedstock for renewable energy production. However, the function of DGAT1 in Chlorella has not been reported. A full-length cDNA encoding a putative diacylglycerol acyltransferase 1 (DGAT1, EC 2.3.1.20) was obtained from Chlorella ellipsoidea. The 2,142 bp open reading frame of this cDNA, designated CeDGAT1, encodes a protein of 713 amino acids showing no more than 40% identity with DGAT1s of higher plants. Transcript analysis showed that the expression level of CeDGAT1 markedly increased under nitrogen starvation, which led to significant triacylglycerol (TAG) accumulation. CeDGAT1 activity was confirmed in the yeast quadruple mutant strain H1246 by restoring its ability to produce TAG. Upon expression of CeDGAT1, the total fatty acid content in wild-type yeast (INVSc1) increased by 142%, significantly higher than that transformed with DGAT1s from higher plants, including even the oil crop soybean. The over-expression of CeDGAT1 under the NOS promoter in wild-type Arabidopsis thaliana and Brassica napus var. Westar significantly increased the oil content by 8-37% and 12-18% and the average 1,000-seed weight by 9-15% and 6-29%, respectively, but did not alter the fatty acid composition of the seed oil. The net increase in the 1,000-seed total lipid content was up to 25-50% in both transgenic Arabidopsis and B. napus. We identified a gene encoding DGAT1 in C. ellipsoidea and confirmed that it plays an important role in TAG accumulation. This is the first functional analysis of DGAT1 in Chlorella. This information is important for understanding lipid synthesis and accumulation in Chlorella and for genetic engineering to enhance oil production in microalgae

Lipid Oxidation in Carriers of Lecithin:Cholesterol Acyltransferase Gene Mutations

PubMed Central

Holleboom, Adriaan G.; Daniil, Georgios; Fu, Xiaoming; Zhang, Renliang; Hovingh, G. Kees; Schimmel, Alinda W.; Kastelein, John J.P.; Stroes, Erik S.G.; Witztum, Joseph L.; Hutten, Barbara A.; Tsimikas, Sotirios; Hazen, Stanley L.; Chroni, Angeliki; Kuivenhoven, Jan Albert

2013-01-01

Objective Lecithin:cholesterol acyltransferase (LCAT) has been shown to play a role in the depletion of lipid oxidation products, but this has so far not been studied in humans. In this study, we investigated processes and parameters relevant to lipid oxidation in carriers of functional LCAT mutations. Methods and Results In 4 carriers of 2 mutant LCAT alleles, 63 heterozygotes, and 63 family controls, we measured activities of LCAT, paraoxonase 1, and platelet-activating factor-acetylhydrolase; levels of lysophosphatidylcholine molecular species, arachidonic and linoleic acids, and their oxidized derivatives; immunodetectable oxidized phospholipids on apolipoprotein (apo) B–containing and apo(a)-containing lipoproteins; IgM and IgG autoantibodies to malondialdehyde-low-density lipoprotein and IgG and IgM apoB-immune complexes; and the antioxidant capacity of high-density lipoprotein (HDL). In individuals with LCAT mutations, plasma LCAT activity, HDL cholesterol, apoA-I, arachidonic acid, and its oxidized derivatives, oxidized phospholipids on apo(a)-containing lipoproteins, HDL-associated platelet-activating factor-acetylhydrolase activity, and the antioxidative capacity of HDL were gene-dose–dependently decreased. Oxidized phospholipids on apoB-containing lipoproteins was increased in heterozygotes (17%; P<0.001) but not in carriers of 2 defective LCAT alleles. Conclusion Carriers of LCAT mutations present with significant reductions in LCAT activity, HDL cholesterol, apoA-I, platelet-activating factor-acetylhydrolase activity, and antioxidative potential of HDL, but this is not associated with parameters of increased lipid peroxidation; we did not observe significant changes in the oxidation products of arachidonic acid and linoleic acid, immunoreactive oxidized phospholipids on apo(a)-containing lipoproteins, and IgM and IgG autoantibodies against malondialdehyde-low-density lipoprotein. These data indicate that plasma LCAT activity, HDL

Interaction of Phospholipase A/Acyltransferase-3 with Pex19p

PubMed Central

Uyama, Toru; Kawai, Katsuhisa; Kono, Nozomu; Watanabe, Masahiro; Tsuboi, Kazuhito; Inoue, Tomohito; Araki, Nobukazu; Arai, Hiroyuki; Ueda, Natsuo

2015-01-01

Phospholipase A/acyltransferase (PLA/AT)-3 (also known as H-rev107 or AdPLA) was originally isolated as a tumor suppressor and was later shown to have phospholipase A1/A2 activity. We have also found that the overexpression of PLA/AT-3 in mammalian cells results in specific disappearance of peroxisomes. However, its molecular mechanism remained unclear. In the present study, we first established a HEK293 cell line, which stably expresses a fluorescent peroxisome marker protein (DsRed2-Peroxi) and expresses PLA/AT-3 in a tetracycline-dependent manner. The treatment with tetracycline, as expected, caused disappearance of peroxisomes within 24 h, as revealed by diffuse signals of DsRed2-Peroxi and a remarkable decrease in a peroxisomal membrane protein, PMP70. A time-dependent decrease in ether-type lipid levels was also seen. Because the activation of LC3, a marker of autophagy, was not observed, the involvement of autophagy was unlikely. Among various peroxins responsible for peroxisome biogenesis, Pex19p functions as a chaperone protein for the transportation of peroxisomal membrane proteins. Immunoprecipitation analysis showed that PLA/AT-3 binds to Pex19p through its N-terminal proline-rich and C-terminal hydrophobic domains. The protein level and enzyme activity of PLA/AT-3 were increased by its coexpression with Pex19p. Moreover, PLA/AT-3 inhibited the binding of Pex19 to peroxisomal membrane proteins, such as Pex3p and Pex11βp. A catalytically inactive point mutant of PLA/AT-3 could bind to Pex19p but did not inhibit the chaperone activity of Pex19p. Altogether, these results suggest a novel regulatory mechanism for peroxisome biogenesis through the interaction between Pex19p and PLA/AT-3. PMID:26018079

Concerted elevation of acyl-coenzyme A:diacylglycerol acyltransferase (DGAT) activity through independent stimulation of mRNA expression of DGAT1 and DGAT2 by carbohydrate and insulin.

PubMed

Meegalla, Rupalie L; Billheimer, Jeffrey T; Cheng, Dong

2002-11-01

Glucose and insulin are anabolic signals which upregulate the transcriptions of a series of lipogenic enzymes to convert excess carbohydrate into triglycerides for efficient energy storage. These enzymes include ATP-citrate lyase (ACL), acetyl-coenzyme A carboxylase (ACC), fatty acid synthase (FAS), and glycerol-3-phosphate acyltransferase (G3PA). Acyl-coenzyme A:diacylglycerol acyltransferase (DGAT) is important to synthesize fatty acids into triglycerides. Two DGATs from different gene families have recently been identified. In the current study, we report that glucose preferentially enhances DGAT1 mRNA expression, whereas insulin specifically increases the level of DGAT2 mRNA. Treatment of adipocytes with glucose and insulin together results in higher DGAT activity in the membrane than cells treated with either of the agents alone, indicating that glucose and insulin have additive effect on DGAT activation. In mice treated with fast/refeeding protocol, DGAT2 mRNA decreased upon fasting and was replenished upon refeeding in adipose tissue and liver. This pattern of change was not observed for DGAT1. Inasmuch as DGAT1 mRNA is less abundant in liver, we suggest that DGAT1 is more involved in fat absorption in the intestine and in basal level triglyceride synthesis in adipose tissue where it is more highly expressed. In contrast, DGAT2 is more likely to play important roles in assembly of de novo synthesized fatty acids into VLDL particles in the liver.

Regulation of diacylglycerol acyltransferase 2 protein stability by gp78-associated endoplasmic-reticulum-associated degradation.

PubMed

Choi, Kwangman; Kim, Hyeongki; Kang, Hyunju; Lee, So-Young; Lee, Sang Jun; Back, Sung Hoon; Lee, Seo Hyun; Kim, M Sun; Lee, Jeong Eun; Park, Ju Young; Kim, Jiye; Kim, Sunhong; Song, Jae-Hyung; Choi, Yura; Lee, Suui; Lee, Hyun-Jun; Kim, Jong Heon; Cho, Sungchan

2014-07-01

Triacylglycerol (TG) is the major form of stored energy in eukaryotic organisms and is synthesized by diacylglycerol acyltransferase (DGAT) in the endoplasmic reticulum (ER). DGAT2, one of the two DGAT enzymes, is barely detectable in cells, even though its mRNA transcripts are maintained at considerable levels. However, little is known about how DGAT2 expression is altered by protein stability. DGAT2 was highly unstable in cells and was rapidly degraded by proteasomes in an ubiquitin-dependent manner. Deletion mutation analysis identified transmembrane domain 1 (TMD1) as a protein degradation signal. TMD1 is also important for ER localization of DGAT2. Moreover, DGAT2 interacted with p97/VCP, a crucial component of the ER-associated degradation (ERAD) pathway, and polyubiquitinated DGAT2 accumulated following treatment with an ERAD inhibitor. Furthermore, gp78, an E3 ligase involved in ERAD, regulates the degradation of DGAT2 through direct interactions and ubiquitination. Consequently, the stabilization of DGAT2 increased the number of lipid droplets in hepatic cells. Therefore, DGAT2 is regulated by gp78-associated ERAD at the post-translational level. © 2014 FEBS.

Expression of Fungal diacylglycerol acyltransferase2 Genes to Increase Kernel Oil in Maize[OA

PubMed Central

Oakes, Janette; Brackenridge, Doug; Colletti, Ron; Daley, Maureen; Hawkins, Deborah J.; Xiong, Hui; Mai, Jennifer; Screen, Steve E.; Val, Dale; Lardizabal, Kathryn; Gruys, Ken; Deikman, Jill

2011-01-01

Maize (Zea mays) oil has high value but is only about 4% of the grain by weight. To increase kernel oil content, fungal diacylglycerol acyltransferase2 (DGAT2) genes from Umbelopsis (formerly Mortierella) ramanniana and Neurospora crassa were introduced into maize using an embryo-enhanced promoter. The protein encoded by the N. crassa gene was longer than that of U. ramanniana. It included 353 amino acids that aligned to the U. ramanniana DGAT2A protein and a 243-amino acid sequence at the amino terminus that was unique to the N. crassa DGAT2 protein. Two forms of N. crassa DGAT2 were tested: the predicted full-length protein (L-NcDGAT2) and a shorter form (S-NcDGAT2) that encoded just the sequences that share homology with the U. ramanniana protein. Expression of all three transgenes in maize resulted in small but statistically significant increases in kernel oil. S-NcDGAT2 had the biggest impact on kernel oil, with a 26% (relative) increase in oil in kernels of the best events (inbred). Increases in kernel oil were also obtained in both conventional and high-oil hybrids, and grain yield was not affected by expression of these fungal DGAT2 transgenes. PMID:21245192

Global alcohol policy and the alcohol industry.

PubMed

Anderson, Peter

2009-05-01

The WHO is preparing its global strategy on alcohol, and, in so doing, has been asked to consult with the alcohol industry on ways it could contribute in reducing the harm done by alcohol. This review asks which is more effective in reducing harm: the regulatory approaches that the industry does not favour; or the educational approaches that it does favour. The current literature overwhelmingly finds that regulatory approaches (including those that manage the price, availability, and marketing of alcohol) reduce the risk of and the experience of alcohol-related harm, whereas educational approaches (including school-based education and public education campaigns) do not, with industry-funded education actually increasing the risk of harm. The alcohol industry should not be involved in making alcohol policy. Its involvement in implementing policy should be restricted to its role as a producer, distributor, and marketer of alcohol. In particular, the alcohol industry should not be involved in educational programmes, as such involvement could actually lead to an increase in harm.

Internet Alcohol Marketing and Underage Alcohol Use.

PubMed

McClure, Auden C; Tanski, Susanne E; Li, Zhigang; Jackson, Kristina; Morgenstern, Matthis; Li, Zhongze; Sargent, James D

2016-02-01

Internet alcohol marketing is not well studied despite its prevalence and potential accessibility and attractiveness to youth. The objective was to examine longitudinal associations between self-reported engagement with Internet alcohol marketing and alcohol use transitions in youth. A US sample of 2012 youths aged 15 to 20 was surveyed in 2011. An Internet alcohol marketing receptivity score was developed, based on number of positive responses to seeing alcohol advertising on the Internet, visiting alcohol brand Web sites, being an online alcohol brand fan, and cued recall of alcohol brand home page images. We assessed the association between baseline marketing receptivity and both ever drinking and binge drinking (≥6 drinks per occasion) at 1-year follow-up with multiple logistic regression, controlling for baseline drinking status, Internet use, sociodemographics, personality characteristics, and peer or parent drinking. At baseline, ever-drinking and binge-drinking prevalence was 55% and 27%, respectively. Many (59%) reported seeing Internet alcohol advertising, but few reported going to an alcohol Web site (6%) or being an online fan (3%). Higher Internet use, sensation seeking, having family or peers who drank, and past alcohol use were associated with Internet alcohol marketing receptivity, and a score of 1 or 2 was independently associated with greater adjusted odds of initiating binge drinking (odds ratio 1.77; 95% confidence interval, 1.13-2.78 and odds ratio 2.15; 95% confidence interval, 1.06-4.37 respectively) but not with initiation of ever drinking. Although high levels of engagement with Internet alcohol marketing were uncommon, most underage youths reported seeing it, and we found a prospective association between receptivity to this type of alcohol marketing and future problem drinking, making additional research and ongoing surveillance important. Copyright © 2016 by the American Academy of Pediatrics.

Internet Alcohol Marketing and Underage Alcohol Use

PubMed Central

McClure, Auden C.; Tanski, Susanne E.; Li, Zhigang; Jackson, Kristina; Morgenstern, Matthis; Li, Zhongze; Sargent, James D.

2016-01-01

BACKGROUND AND OBJECTIVE Internet alcohol marketing is not well studied despite its prevalence and potential accessibility and attractiveness to youth. The objective was to examine longitudinal associations between self-reported engagement with Internet alcohol marketing and alcohol use transitions in youth. METHODS A US sample of 2012 youths aged 15 to 20 was surveyed in 2011. An Internet alcohol marketing receptivity score was developed, based on number of positive responses to seeing alcohol advertising on the Internet, visiting alcohol brand Web sites, being an online alcohol brand fan, and cued recall of alcohol brand home page images. We assessed the association between baseline marketing receptivity and both ever drinking and binge drinking (≥6 drinks per occasion) at 1-year follow-up with multiple logistic regression, controlling for baseline drinking status, Internet use, sociodemographics, personality characteristics, and peer or parent drinking. RESULTS At baseline, ever-drinking and binge-drinking prevalence was 55% and 27%, respectively. Many (59%) reported seeing Internet alcohol advertising, but few reported going to an alcohol Web site (6%) or being an online fan (3%). Higher Internet use, sensation seeking, having family or peers who drank, and past alcohol use were associated with Internet alcohol marketing receptivity, and a score of 1 or 2 was independently associated with greater adjusted odds of initiating binge drinking (odds ratio 1.77; 95% confidence interval, 1.13–2.78 and odds ratio 2.15; 95% confidence interval, 1.06–4.37 respectively) but not with initiation of ever drinking. CONCLUSIONS Although high levels of engagement with Internet alcohol marketing were uncommon, most underage youths reported seeing it, and we found a prospective association between receptivity to this type of alcohol marketing and future problem drinking, making additional research and ongoing surveillance important. PMID:26738886

Alcoholic and non-alcoholic steatohepatitis

PubMed Central

Neuman, Manuela G.; French, Samuel W.; French, Barbara A.; Seitz, Helmut K.; Cohen, Lawrence B.; Mueller, Sebastian; Osna, Natalia A.; Kharbanda, Kusum K.; Seth, Devanshi; Bautista, Abraham; Thompson, Kyle J.; McKillop, Iain H.; Kirpich, Irina A.; McClain, Craig J.; Bataller, Ramon; Nanau, Radu M.; Voiculescu, Mihai; Opris, Mihai; Shen, Hong; Tillman, Brittany; Li, Jun; Liu, Hui; Thomas, Paul G.; Ganesan, Murali; Malnick, Steve

2015-01-01

This paper is based upon the “Charles Lieber Satellite Symposia” organized by Manuela G. Neuman at the Research Society on Alcoholism (RSA) Annual Meetings, 2013 and 2014. The present review includes pre-clinical, translational and clinical research that characterize alcoholic liver disease (ALD) and non-alcoholic steatohepatitis (NASH). In addition, a literature search in the discussed area was performed. Strong clinical and experimental evidence lead to recognition of the key toxic role of alcohol in the pathogenesis of ALD. The liver biopsy can confirm the etiology of NASH or alcoholic steatohepatitis (ASH) and assess structural alterations of cells, their organelles, as well as inflammatory activity. Three histological stages of ALD are simple steatosis, ASH, and chronic hepatitis with hepatic fibrosis or cirrhosis. These latter stages may also be associated with a number of cellular and histological changes, including the presence of Mallory's hyaline, megamitochondria, or perivenular and perisinusoidal fibrosis. Genetic polymorphisms of ethanol metabolizing enzymes such as cytochrome p450 (CYP) 2E1 activation may change the severity of ASH and NASH. Alcohol mediated hepatocarcinogenesis, immune response to alcohol in ASH, as well as the role of other risk factors such as its comorbidities with chronic viral hepatitis in the presence or absence of human deficiency virus are discussed. Dysregulation of hepatic methylation, as result of ethanol exposure, in hepatocytes transfected with hepatitis C virus (HCV), illustrates an impaired interferon signaling. The hepatotoxic effects of ethanol undermine the contribution of malnutrition to the liver injury. Dietary interventions such as micro and macronutrients, as well as changes to the microbiota are suggested. The clinical aspects of NASH, as part of metabolic syndrome in the aging population, are offered. The integrative symposia investigate different aspects of alcohol-induced liver damage and possible

The enzyme lecithin-cholesterol acyltransferase esterifies cerebrosterol and limits the toxic effect of this oxysterol on SH-SY5Y cells.

PubMed

La Marca, Valeria; Spagnuolo, Maria Stefania; Cigliano, Luisa; Marasco, Daniela; Abrescia, Paolo

2014-07-01

Cholesterol is mostly removed from the CNS by its conversion to cerebrosterol (24(S)-hydroxycholesterol, 24(S)OH-C), which is transported to the circulation for bile formation in liver. A neurotoxic role of this oxysterol was previously demonstrated in cell culture. Here, we provide evidence that the enzyme lecithin-cholesterol acyltransferase, long known to esterify cholesterol, also produces monoesters of 24(S)OH-C. Proteoliposomes containing apolipoprotein A-I or apolipoprotein E were used to stimulate the enzyme activity and entrap the formed esters. Proteoliposomes with apolipoprotein A-I were found to be more active than those with apolipoprotein E in stimulating the production of oxysteryl esters. Cholesterol and 24(S)OH-C were found to compete for enzyme activity. High levels of haptoglobin, as those circulating during the acute inflammatory phase, inhibited 24(S)OH-C esterification. When highly neurotoxic 24(S)OH-C was treated with enzyme and proteoliposomes before incubation with differentiated SH-SY5Y cells, the neuron survival improved. The esters of 24(S)OH-C, embedded into proteoliposomes by the enzyme and isolated from unesterified 24(S)OH-C by gel filtration chromatography, did not enter the neurons in culture. These results suggest that the enzyme, in the presence of the apolipoproteins, converts 24(S)OH-C into esters restricted to the extracellular environment, thus preventing or limiting oxysterol-induced neurotoxic injuries to neurons in culture. 24-hydroxycholesterol (24(S)OH-C) is neurotoxic. The enzyme lecithin-cholesterol acyltransferase (LCAT) synthesizes monoesters of 24(S)OH-C in reaction mixtures with proteoliposomes containing phospholipids and apolipoprotein A-I or apolipoprotein E. The esters, also produced by incubation of cerebrospinal fluid only with tritiated 24(S)OH-C, are embedded into lipoproteins that do not enter neurons in culture. The enzyme activity limits the toxicity of 24-hydroxycholesterol in neuron culture. © 2014

Varenicline Reduces Alcohol Intake During Repeated Cycles of Alcohol Reaccess Following Deprivation in Alcohol-Preferring (P) Rats.

PubMed

Froehlich, Janice C; Nicholson, Emily R; Dilley, Julian E; Filosa, Nick J; Rademacher, Logan C; Smith, Teal N

2017-08-01

Most alcoholics experience periods of voluntary alcohol abstinence or imposed alcohol deprivation followed by a return to alcohol drinking. This study examined whether varenicline (VAR) reduces alcohol intake during a return to drinking after periods of alcohol deprivation in rats selectively bred for high alcohol drinking (the alcohol preferring or "P" rats). Alcohol-experienced P rats were given 24-hour access to food and water and scheduled access to alcohol (15% and 30% v/v) for 2 h/d. After 4 weeks, rats were deprived of alcohol for 2 weeks, followed by reaccess to alcohol for 2 weeks, and this pattern was repeated for a total of 3 cycles. Rats were fed either vehicle (VEH) or VAR, in doses of 0.5, 1.0, or 2.0 mg/kg BW, at 1 hour prior to onset of the daily alcohol reaccess period for the first 5 days of each of the 3 alcohol reaccess cycles. Low-dose VAR (0.5 mg/kg BW) reduced alcohol intake during the 5 days of drug treatment in alcohol reaccess cycles 1 and 2. Higher doses of VAR (1.0 mg/kg BW and 2.0 mg/kg BW) reduced alcohol intake during the 5 days of treatment in all 3 alcohol reaccess cycles. The decrease in alcohol intake disappeared with termination of VAR treatment in all alcohol reaccess cycles. The results demonstrate that VAR decreases alcohol intake during multiple cycles of alcohol reaccess following alcohol deprivation in rats and suggests that it may prevent a return to heavy alcohol drinking during a lapse from alcohol abstinence in humans with alcohol use disorder. Copyright © 2017 by the Research Society on Alcoholism.

Mangiferin treatment inhibits hepatic expression of acyl-coenzyme A:diacylglycerol acyltransferase-2 in fructose-fed spontaneously hypertensive rats: a link to amelioration of fatty liver.

PubMed

Xing, Xiaomang; Li, Danyang; Chen, Dilong; Zhou, Liang; Chonan, Ritsu; Yamahara, Johji; Wang, Jianwei; Li, Yuhao

2014-10-15

Mangiferin, a xanthone glucoside, and its associated traditional herbs have been demonstrated to improve abnormalities of lipid metabolism. However, its underlying mechanisms remain largely unclear. This study investigated the anti-steatotic effect of mangiferin in fructose-fed spontaneously hypertensive rat (SHR)s that have a mutation in sterol regulatory element binding protein (SREBP)-1. The results showed that co-administration of mangiferin (15 mg/kg, once daily, by oral gavage) over 7 weeks dramatically diminished fructose-induced increases in hepatic triglyceride content and Oil Red O-stained area in SHRs. However, blood pressure, fructose and chow intakes, white adipose tissue weight and metabolic parameters (plasma concentrations of glucose, insulin, triglyceride, total cholesterol and non-esterified fatty acids) were unaffected by mangiferin treatment. Mechanistically, mangiferin treatment suppressed acyl-coenzyme A:diacylglycerol acyltransferase (DGAT)-2 expression at the mRNA and protein levels in the liver. In contrast, mangiferin treatment was without effect on hepatic mRNA and/or protein expression of SREBP-1/1c, carbohydrate response element binding protein, liver pyruvate kinase, fatty acid synthase, acetyl-CoA carboxylase-1, stearoyl-CoA desaturase-1, DGAT-1, monoacyglycerol acyltransferase-2, microsomal triglyceride transfer protein, peroxisome proliferator-activated receptor-alpha, carnitine palmitoyltransferase-1 and acyl-CoA oxidase. Collectively, our results suggest that mangiferin treatment ameliorates fatty liver in fructose-fed SHRs by inhibiting hepatic DGAT-2 that catalyzes the final step in triglyceride biosynthesis. The anti-steatotic effect of mangiferin may occur independently of the hepatic signals associated with de novo fatty acid synthesis and oxidation. Copyright © 2014 Elsevier Inc. All rights reserved.

Perspectives on the neuroscience of alcohol from the National Institute on Alcohol Abuse and Alcoholism.

PubMed

Reilly, Matthew T; Noronha, Antonio; Warren, Kenneth

2014-01-01

Mounting evidence over the last 40 years clearly indicates that alcoholism (alcohol dependence) is a disorder of the brain. The National Institute on Alcohol Abuse and Alcoholism (NIAAA) has taken significant steps to advance research into the neuroscience of alcohol. The Division of Neuroscience and Behavior (DNB) was formed within NIAAA in 2002 to oversee, fund, and direct all research areas that examine the effects of alcohol on the brain, the genetic underpinnings of alcohol dependence, the neuroadaptations resulting from excessive alcohol consumption, advanced behavioral models of the various stages of the addiction cycle, and preclinical medications development. This research portfolio has produced important discoveries in the etiology, treatment, and prevention of alcohol abuse and dependence. Several of these salient discoveries are highlighted and future areas of neuroscience research on alcohol are presented. © 2014 Elsevier B.V. All rights reserved.

Parental Alcohol Involvement and Adolescent Alcohol Expectancies Predict Alcohol Involvement in Male Adolescents

PubMed Central

Cranford, James A.; Zucker, Robert A.; Jester, Jennifer M.; Puttler, Leon I.; Fitzgerald, Hiram E.

2010-01-01

Current models of adolescent drinking behavior hypothesize that alcohol expectancies mediate the effects of other proximal and distal risk factors. This longitudinal study tested the hypothesis that the effects of parental alcohol involvement on their children’s drinking behavior in mid-adolescence are mediated by the children’s alcohol expectancies in early adolescence. A sample of 148 initially 9–11 year old boys and their parents from a high-risk population and a contrast group of community families completed measures of drinking behavior and alcohol expectancies over a 6-year interval. We analyzed data from middle childhood (M age = 10.4 years), early adolescence (M age = 13.5 years), and mid-adolescence (M age = 16.5 years). The sample was restricted only to adolescents who had begun to drink by mid-adolescence. Results from zero-inflated Poisson regression analyses showed that 1) maternal drinking during their children’s middle childhood predicted number of drinking days in middle adolescence; 2) negative and positive alcohol expectancies in early adolescence predicted odds of any intoxication in middle adolescence; and 3) paternal alcoholism during their children’s middle childhood and adolescents’ alcohol expectancies in early adolescence predicted frequency of intoxication in middle adolescence. Contrary to predictions, child alcohol expectancies did not mediate the effects of parental alcohol involvement in this high-risk sample. Different aspects of parental alcohol involvement, along with early adolescent alcohol expectancies, independently predicted adolescent drinking behavior in middle adolescence. Alternative pathways for the influence of maternal and paternal alcohol involvement and implications for expectancy models of adolescent drinking behavior were discussed. PMID:20853923

Microscale High-Throughput Experimentation as an Enabling Technology in Drug Discovery: Application in the Discovery of (Piperidinyl)pyridinyl-1H-benzimidazole Diacylglycerol Acyltransferase 1 Inhibitors.

PubMed

Cernak, Tim; Gesmundo, Nathan J; Dykstra, Kevin; Yu, Yang; Wu, Zhicai; Shi, Zhi-Cai; Vachal, Petr; Sperbeck, Donald; He, Shuwen; Murphy, Beth Ann; Sonatore, Lisa; Williams, Steven; Madeira, Maria; Verras, Andreas; Reiter, Maud; Lee, Claire Heechoon; Cuff, James; Sherer, Edward C; Kuethe, Jeffrey; Goble, Stephen; Perrotto, Nicholas; Pinto, Shirly; Shen, Dong-Ming; Nargund, Ravi; Balkovec, James; DeVita, Robert J; Dreher, Spencer D

2017-05-11

Miniaturization and parallel processing play an important role in the evolution of many technologies. We demonstrate the application of miniaturized high-throughput experimentation methods to resolve synthetic chemistry challenges on the frontlines of a lead optimization effort to develop diacylglycerol acyltransferase (DGAT1) inhibitors. Reactions were performed on ∼1 mg scale using glass microvials providing a miniaturized high-throughput experimentation capability that was used to study a challenging S N Ar reaction. The availability of robust synthetic chemistry conditions discovered in these miniaturized investigations enabled the development of structure-activity relationships that ultimately led to the discovery of soluble, selective, and potent inhibitors of DGAT1.

[Alcohol].

PubMed

Zima, T

1996-07-14

Alcohol is one of the most widely used addictive substances. It can be assumed that everybody encounters alcohol--ethanol in various forms and concentrations in the course of their lives. A global and social problem of our civilization is alcohol consumption which has a rising trend. Since 1989 the consumption of alcoholic beverages is rising and the mean annual consumption of concentrated ethanol per head is cea 10 litres. In ethanol abuse the organism is damaged not only by ethanol alone but in particular by substances formed during its metabolism. Its detailed knowledge is essential for the knowledge and investigations of the metabolic and toxic effect of ethanol on the organism. Ingested alcohol is in 90-98% eliminated from the organism by three known metabolic pathways: 1-alcohol dehydrogenase, 2-the microsomal ethanol oxidizing system and 3-catalase. Alcohol is a frequent important risk factor of serious "diseases of civilization" such as IHD, hypertension, osteoporosis, neoplastic diseases. Cirrhosis of the liver and chronic pancreatitis are the well known diseases associated with alcohol ingestion and also their most frequent cause. It is impossible to list all organs and diseases which develop as a result of alcohol consumption. It is important to realize that regular and "relatively" small amounts in the long run damage the organism and may be even fatal.

Sesquiterpenoids isolated from the flower buds of Tussilago farfara L. inhibit diacylglycerol acyltransferase.

PubMed

Park, Hye Ran; Yoo, Mi Young; Seo, Jee Hee; Kim, Il Soon; Kim, Nam Ye; Kang, Ji Yun; Cui, Long; Lee, Chang-Soo; Lee, Chul-Ho; Lee, Hyun Sun

2008-11-26

Inhibition of acyl CoA:diacylglycerol acyltransferase (DGAT), which is a key enzyme in triglyceride synthesis in eukaryotic organisms, has been proposed as one of the drug targets for treating obesity, type II diabetes mellitus, and metabolic syndrome. Bioassay-guided fractionation of EtOH extract of the flower buds of Tussilago farfara , using an in vitro DGAT enzyme assay, resulted in the isolation of four known sesquiterpenoids, tussilagonone (1), tussilagone (2), 7beta-(3-ethyl-cis-crotonoyloxy)-1alpha-(2-methylbutyryloxy)-3,14-dehydro-Z-notonipetranone (3), and 8-angeloylxy-3,4-epoxy-bisabola-7(14),10-dien-2-one (4). DGAT1 inhibitory activity was studied by in vitro DGAT assay using rat liver microsomes and HepG2 cell microsomes. They showed DGAT1 inhibition with IC(50) values of 99.2 (1), 18.8 (2), 47.0 (3), and 211.1 (4) microM (for rat liver microsomes) and >1 mM (1), 49.1 (2), 160.7 (3), and 294.4 (4) microM (for HepG2 cell microsomes), respectively. Compound 2 showed the most potent inhibition against microsomal DGAT1 derived from rat liver and human hepatocellular carcinoma HepG2 cells and also significantly inhibited triglyceride synthesis by suppressing incorporation of [(14)C]acetate or [(14)C]glycerol into triglycerides in HepG2 cells. These findings suggest that tussilagone is a potential lead compound in the treatment of obesity and type 2 diabetes.

Lecithin-cholesterol acyltransferase in brain: Does oxidative stress influence the 24-hydroxycholesterol esterification?

PubMed

La Marca, Valeria; Maresca, Bernardetta; Spagnuolo, Maria Stefania; Cigliano, Luisa; Dal Piaz, Fabrizio; Di Iorio, Giuseppe; Abrescia, Paolo

2016-04-01

24-Hydroxycholesterol (24OH-C) is esterified by the enzyme lecithin-cholesterol acyltransferase (LCAT) in the cerebrospinal fluid (CSF). We report here that the level of 24OH-C esters was lower in CSF of patients with amyotrophic lateral sclerosis than in healthy subjects (54% vs 68% of total 24OH-C, p=0.0005; n=8). Similarly, the level of 24OH-C esters in plasma was lower in patients than in controls (62% vs 77% of total 24OH-C; p=0.0076). The enzyme amount in CSF, as measured by densitometry of the protein band revealed by immunoblotting, was about 4-fold higher in patients than in controls (p=0.0085). As differences in the concentration of the LCAT stimulator Apolipoprotein E were not found, we hypothesized that the reduced 24OH-C esterification in CSF of patients might depend on oxidative stress. We actually found that oxidative stress reduced LCAT activity in vitro, and 24OH-C effectively stimulated the enzyme secretion from astrocytoma cells in culture. Enhanced LCAT secretion from astrocytes might represent an adaptive response to the increase of non-esterified 24OH-C percentage, aimed to avoid the accumulation of this neurotoxic compound. The low degree of 24OH-C esterification in CSF or plasma might reflect reduced activity of LCAT during neurodegeneration. Copyright © 2015 Elsevier Ireland Ltd and the Japan Neuroscience Society. All rights reserved.

Alcohol

MedlinePlus

... because that's how many accidents occur. What Is Alcoholism? What can be confusing about alcohol is that ... develop a problem with it. Sometimes, that's called alcoholism (say: al-kuh-HOL - ism) or being an ...

Alcohol, microbiome, life style influence alcohol and non-alcoholic organ damage.

PubMed

Neuman, Manuela G; French, Samuel W; Zakhari, Samir; Malnick, Stephen; Seitz, Helmut K; Cohen, Lawrence B; Salaspuro, Mikko; Voinea-Griffin, Andreea; Barasch, Andrei; Kirpich, Irina A; Thomes, Paul G; Schrum, Laura W; Donohue, Terrence M; Kharbanda, Kusum K; Cruz, Marcus; Opris, Mihai

2017-02-01

This paper is based upon the "8th Charles Lieber's Satellite Symposium" organized by Manuela G. Neuman at the Research Society on Alcoholism Annual Meeting, on June 25, 2016 at New Orleans, Louisiana, USA. The integrative symposium investigated different aspects of alcohol-induced liver disease (ALD) as well as non-alcohol-induced liver disease (NAFLD) and possible repair. We revealed the basic aspects of alcohol metabolism that may be responsible for the development of liver disease as well as the factors that determine the amount, frequency and which type of alcohol misuse leads to liver and gastrointestinal diseases. We aimed to (1) describe the immuno-pathology of ALD, (2) examine the role of genetics in the development of alcoholic hepatitis (ASH) and NAFLD, (3) propose diagnostic markers of ASH and non-alcoholic steatohepatitis (NASH), (4) examine age and ethnic differences as well as analyze the validity of some models, (5) develop common research tools and biomarkers to study alcohol-induced effects, 6) examine the role of alcohol in oral health and colon and gastrointestinal cancer and (7) focus on factors that aggravate the severity of organ-damage. The present review includes pre-clinical, translational and clinical research that characterizes ALD and NAFLD. Strong clinical and experimental evidence lead to recognition of the key toxic role of alcohol in the pathogenesis of ALD with simple fatty infiltrations and chronic alcoholic hepatitis with hepatic fibrosis or cirrhosis. These latter stages may also be associated with a number of cellular and histological changes, including the presence of Mallory's hyaline, megamitochondria, or perivenular and perisinusoidal fibrosis. Genetic polymorphisms of ethanol metabolizing enzymes and cytochrome p450 (CYP) 2E1 activation may change the severity of ASH and NASH. Other risk factors such as its co-morbidities with chronic viral hepatitis in the presence or absence of human deficiency virus were discussed

A type 2 diacylglycerol acyltransferase accelerates the triacylglycerol biosynthesis in heterokont oleaginous microalga Nannochloropsis oceanica.

PubMed

Li, Da-Wei; Cen, Shi-Ying; Liu, Yu-Hong; Balamurugan, Srinivasan; Zheng, Xin-Yan; Alimujiang, Adili; Yang, Wei-Dong; Liu, Jie-Sheng; Li, Hong-Ye

2016-07-10

Oleaginous microalgae have received a considerable attention as potential biofuel feedstock. However, lack of industry-suitable strain with lipid rich biomass limits its commercial applications. Targeted engineering of lipogenic pathways represents a promising strategy to enhance the efficacy of microalgal oil production. In this study, a type 2 diacylglycerol acyltransferase (DGAT), a rate-limiting enzyme in triacylglycerol (TAG) biosynthesis, was identified and overexpressed in heterokont oleaginous microalga Nannochloropsis oceanica for the first time. Overexpression of DGAT2 in Nannochloropsis increased the relative transcript abundance by 3.48-fold in engineered microalgae cells. TAG biosynthesis was subsequently accelerated by DGAT2 overexpression and neutral lipid content was significantly elevated by 69% in engineered microalgae. The fatty acid profile determined by GC-MS revealed that fatty acid composition was altered in engineered microalgae. Saturated fatty acids and polyunsaturated fatty acids were found to be increased whereas monounsaturated fatty acids content decreased. Furthermore, DGAT2 overexpression did not show negative impact on algal growth parameters. The present investigation showed that the identified DGAT2 would be a potential candidate for enhancing TAG biosynthesis and might facilitate the development of promising oleaginous strains with industrial potential. Copyright © 2016 Elsevier B.V. All rights reserved.

Acute sterol o-acyltransferase 2 (SOAT2) knockdown rapidly mobilizes hepatic cholesterol for fecal excretion.

PubMed

Marshall, Stephanie M; Gromovsky, Anthony D; Kelley, Kathryn L; Davis, Matthew A; Wilson, Martha D; Lee, Richard G; Crooke, Rosanne M; Graham, Mark J; Rudel, Lawrence L; Brown, J Mark; Temel, Ryan E

2014-01-01

The primary risk factor for atherosclerotic cardiovascular disease is LDL cholesterol, which can be reduced by increasing cholesterol excretion from the body. Fecal cholesterol excretion can be driven by a hepatobiliary as well as a non-biliary pathway known as transintestinal cholesterol efflux (TICE). We previously showed that chronic knockdown of the hepatic cholesterol esterifying enzyme sterol O-acyltransferase 2 (SOAT2) increased fecal cholesterol loss via TICE. To elucidate the initial events that stimulate TICE, C57Bl/6 mice were fed a high cholesterol diet to induce hepatic cholesterol accumulation and were then treated for 1 or 2 weeks with an antisense oligonucleotide targeting SOAT2. Within 2 weeks of hepatic SOAT2 knockdown (SOAT2HKD), the concentration of cholesteryl ester in the liver was reduced by 70% without a reciprocal increase in hepatic free cholesterol. The rapid mobilization of hepatic cholesterol stores resulted in a ∼ 2-fold increase in fecal neutral sterol loss but no change in biliary cholesterol concentration. Acute SOAT2HKD increased plasma cholesterol carried primarily in lipoproteins enriched in apoB and apoE. Collectively, our data suggest that acutely reducing SOAT2 causes hepatic cholesterol to be swiftly mobilized and packaged onto nascent lipoproteins that feed cholesterol into the TICE pathway for fecal excretion.

Beta2-adrenergic activity modulates vascular tone regulation in lecithin:cholesterol acyltransferase knockout mice.

PubMed

Manzini, S; Pinna, C; Busnelli, M; Cinquanta, P; Rigamonti, E; Ganzetti, G S; Dellera, F; Sala, A; Calabresi, L; Franceschini, G; Parolini, C; Chiesa, G

2015-11-01

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. Aortas from wild-type (Lcat(wt)) and LCAT knockout (Lcat(KO)) mice exposed to noradrenaline showed reduced contractility in Lcat(KO) mice (P<0.005), whereas acetylcholine exposure showed a lower NO-dependent relaxation in Lcat(KO) mice (P<0.05). Quantitative PCR and Western blotting analyses suggested an adequate eNOS expression in Lcat(KO) mouse aortas. Real-time PCR analysis indicated increased expression of β2-adrenergic receptors vs wild-type mice. Aorta stimulation with noradrenaline in the presence of propranolol, to abolish the β-mediated relaxation, showed the same contractile response in the two mouse lines. Furthermore, propranolol pretreatment of mouse aortas exposed to L-NAME prevented the difference in responses between Lcat(wt) and Lcat(KO) mice. The results indicate that LCAT deficiency leads to increased β2-adrenergic relaxation and to a consequently decreased NO-mediated vasodilation that can be reversed to guarantee a correct vascular tone. The present study suggests that LCAT deficiency is not associated with an impaired vascular reactivity. Copyright © 2015. Published by Elsevier Inc.

Beta2-adrenergic activity modulates vascular tone regulation in lecithin:cholesterol acyltransferase knockout mice

PubMed Central

Manzini, S.; Pinna, C.; Busnelli, M.; Cinquanta, P.; Rigamonti, E.; Ganzetti, G.S.; Dellera, F.; Sala, A.; Calabresi, L.; Franceschini, G.; Parolini, C.; Chiesa, G.

2015-01-01

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. Aortas from wild-type (Lcatwt) and LCAT knockout (LcatKO) mice exposed to noradrenaline showed reduced contractility in LcatKO mice (P < 0.005), whereas acetylcholine exposure showed a lower NO-dependent relaxation in LcatKO mice (P < 0.05). Quantitative PCR and Western blotting analyses suggested an adequate eNOS expression in LcatKO mouse aortas. Real-time PCR analysis indicated increased expression of β2-adrenergic receptors vs wild-type mice. Aorta stimulation with noradrenaline in the presence of propranolol, to abolish the β-mediated relaxation, showed the same contractile response in the two mouse lines. Furthermore, propranolol pretreatment of mouse aortas exposed to L-NAME prevented the difference in responses between Lcatwt and LcatKO mice. The results indicate that LCAT deficiency leads to increased β2-adrenergic relaxation and to a consequently decreased NO-mediated vasodilation that can be reversed to guarantee a correct vascular tone. The present study suggests that LCAT deficiency is not associated with an impaired vascular reactivity. PMID:26254103

Receptivity to alcohol marketing predicts initiation of alcohol use.

PubMed

Henriksen, Lisa; Feighery, Ellen C; Schleicher, Nina C; Fortmann, Stephen P

2008-01-01

This longitudinal study examined the influence of alcohol advertising and promotions on the initiation of alcohol use. A measure of receptivity to alcohol marketing was developed from research about tobacco marketing. Recall and recognition of alcohol brand names were also examined. Data were obtained from in-class surveys of sixth, seventh, and eighth graders at baseline and 12-month follow-up. Participants who were classified as never drinkers at baseline (n = 1,080) comprised the analysis sample. Logistic regression models examined the association of advertising receptivity at baseline with any alcohol use and current drinking at follow-up, adjusting for multiple risk factors, including peer alcohol use, school performance, risk taking, and demographics. At baseline, 29% of never drinkers either owned or wanted to use an alcohol branded promotional item (high receptivity), 12% students named the brand of their favorite alcohol ad (moderate receptivity), and 59% were not receptive to alcohol marketing. Approximately 29% of adolescents reported any alcohol use at follow-up; 13% reported drinking at least 1 or 2 days in the past month. Never drinkers who reported high receptivity to alcohol marketing at baseline were 77% more likely to initiate drinking by follow-up than those were not receptive. Smaller increases in the odds of alcohol use at follow-up were associated with better recall and recognition of alcohol brand names at baseline. Alcohol advertising and promotions are associated with the uptake of drinking. Prevention programs may reduce adolescents' receptivity to alcohol marketing by limiting their exposure to alcohol ads and promotions and by increasing their skepticism about the sponsors' marketing tactics.

Receptivity to alcohol marketing predicts initiation of alcohol use

PubMed Central

Henriksen, Lisa; Feighery, Ellen C.; Schleicher, Nina C.; Fortmann, Stephen P.

2008-01-01

Purpose This longitudinal study examined the influence of alcohol advertising and promotions on the initiation of alcohol use. A measure of receptivity to alcohol marketing was developed from research about tobacco marketing. Recall and recognition of alcohol brand names were also examined. Methods Data were obtained from in-class surveys of 6th, 7th, and 8th graders at baseline and 12-month follow-up. Participants who were classified as never drinkers at baseline (n=1,080) comprised the analysis sample. Logistic regression models examined the association of advertising receptivity at baseline with any alcohol use and current drinking at follow-up, adjusting for multiple risk factors, including peer alcohol use, school performance, risk taking, and demographics. Results At baseline, 29% of never drinkers either owned or wanted to use an alcohol branded promotional item (high receptivity), 12% students named the brand of their favorite alcohol ad (moderate receptivity) and 59% were not receptive to alcohol marketing. Approximately 29% of adolescents reported any alcohol use at follow-up; 13% reported drinking at least 1 or 2 days in the past month. Never drinkers who reported high receptivity to alcohol marketing at baseline were 77% more likely to initiate drinking by follow-up than those were not receptive. Smaller increases in the odds of alcohol use at follow-up were associated with better recall and recognition of alcohol brand names at baseline. Conclusions Alcohol advertising and promotions are associated with the uptake of drinking. Prevention programs may reduce adolescents’ receptivity to alcohol marketing by limiting their exposure to alcohol ads and promotions and by increasing their skepticism about the sponsors’ marketing tactics. PMID:18155027

The economic impact of alcohol abuse and alcoholism.

PubMed

Burke, T R

1988-01-01

The economic effects of alcohol abuse are as damaging to the nation as the health effects, affecting the family, the community, and persons of all ages. Underaged drinking is interfering with children's development, affecting the nation's ability to respond to economic challenge in the future. The college aged may be the most difficult to educate about alcohol abuse because of drinking patterns established at an early age and susceptibility to advertising inducements. Health care costs for families with an alcoholic member are twice those for families without one, and up to half of all emergency room admissions are alcohol related. Fetal alcohol syndrome is one of the top three known causes of birth defects, and is totally preventable. Alcohol abuse and alcoholism are estimated to have cost the nation $117 billion in 1983, while nonalcoholic drug abuse that year cost $60 billion. Costs of alcohol abuse are expected to be $136 billion a year by 1990, mostly from lost productivity and employment. Between 6 and 7 million workers are alcoholic, with an undetermined loss of productivity, profits, and competitiveness of American business. Alcohol abuse contributes to the high health care costs of the elderly beneficiaries of Federal health financing programs. Heavily affected minorities include blacks, Hispanics, and Native Americans. Society tends to treat the medical and social consequences of alcohol abuse, rather than its causes. Although our experience with the consequences of alcohol abuse is greater than that for any other drug, public concern for its prevention and treatment is less than for other major illnesses or abuse of other drugs. Alcohol abuse is a problem being given high priority within the Department in an effort to create a national agenda on the issue and to try to impart a greater sense of urgency about the problems. Ways are being explored to integrate alcoholism activities into more Departmental programs. Employee assistance programs for alcohol

Endogenous ghrelin-O-acyltransferase (GOAT) acylates local ghrelin in the hippocampus.

PubMed

Murtuza, Mohammad I; Isokawa, Masako

2018-01-01

Ghrelin is an appetite-stimulating peptide. Serine 3 on ghrelin must be acylated by octanoate via the enzyme ghrelin-O-acyltransferase (GOAT) for the peptide to bind and activate the cognate receptor, growth hormone secretagogue receptor type 1a (GHSR1a). Interest in GHSR1a increased dramatically when GHSR1a mRNA was demonstrated to be widespread in the brain, including the cortex and hippocampus, indicating that it has multifaceted functions beyond the regulation of metabolism. However, the source of octanoylated ghrelin for GHSR1a in the brain, outside of the hypothalamus, is not well understood. Here, we report the presence of GOAT and its ability to acylate non-octanoylated ghrelin in the hippocampus. GOAT immunoreactivity is aggregated at the base of the dentate granule cell layer in the rat and wild-type mouse. This immunoreactivity was not affected by the pharmacological inhibition of GHSR1a or the metabolic state-dependent fluctuation of systemic ghrelin levels. However, it was absent in the GHSR1a knockout mouse hippocampus, pointing the possibility that the expression of GHSR1a may be a prerequisite for the production of GOAT. Application of fluorescein isothiocyanate (FITC)-conjugated non-octanoylated ghrelin in live hippocampal slice culture (but not in fixed culture or in the presence of GOAT inhibitors) mimicked the binding profile of FITC-conjugated octanoylated ghrelin, suggesting that extracellularly applied non-octanoylated ghrelin was acylated by endogenous GOAT in the live hippocampus while GOAT being mobilized out of neurons. Our results will advance the understanding for the role of endogenous GOAT in the hippocampus and facilitate the search for the source of ghrelin that is intrinsic to the brain. © 2017 International Society for Neurochemistry.

Enzymatic synthesis of dithiolopyrrolone antibiotics using cell-free extract of Saccharothrix algeriensis NRRL B-24137 and biochemical characterization of two pyrrothine N-acyltransferases in this extract.

PubMed

Saker, Safwan; Almousa Almaksour, Ziade; Chorin, Anne-Claire; Lebrihi, Ahmed; Mathieu, Florence

2014-01-01

Saccharothrix algeriensis NRRL B-24137 produces naturally different dithiolopyrrolone derivatives. The enzymatic activity of pyrrothine N-acyltransferase was determined to be responsible for the transfer of an acyl group from acyl-CoA to pyrrothine core. This activity was also reported to be responsible for the diversity of the dithiolopyrrolone derivatives. Based on this fact, nine dithiolopyrrolone derivatives were produced in vitro via the crude extract of Sa. algeriensis. Three of them have never been obtained before by natural fermentation: acetoacetyl-pyrrothine, hydroxybutyryl-pyrrothine, and dimethyl thiolutin (holomycin). Two acyltransferase activities, acetyltransferase and benzoyltransferase catalyzing the incorporation of linear and cyclic acyl groups to the pyrrothine core, respectively, were biochemically characterized in this crude extract. The first one is responsible for formation of acetyl-pyrrothine and the second for benzoyl-pyrrothine. Both enzymes were sensitive to temperature changes: For example, the loss of acetyltransferase and benzoyltransferase activity was 53% and 80% respectively after pre-incubation of crude extract for 60 min at 20°C. The two enzymes were more active in neutral and basal media (pH 7-10) than in the acidic one (pH 3-6). The optimum temperature and pH of acetyltransferase were 40°C and 7, with a Km value of 7.9 μM and a Vmax of 0.63 μM/min when acetyl-CoA was used as limited substrate. Benzoyltransferase had a temperature and a pH optimum at 55°C and 9, a Km value of 14.7 μM, and a Vmax of 0.67 μM/min when benzoyl- CoA was used as limited substrate.

Alcoholism - resources

MedlinePlus

Resources - alcoholism ... The following organizations are good resources for information on alcoholism : Alcoholics Anonymous -- www.aa.org Al-Anon Family Groups www.al-anon.org National Institute on Alcohol ...

Fetal alcohol effects in alcoholic veteran patients.

PubMed

Tishler, P V; Henschel, C E; Ngo, T A; Walters, E E; Worobec, T G

1998-11-01

Fetal alcohol syndrome is often associated with severe physical and neuropsychiatric maldevelopment. On the other hand, some offspring of women who drank during pregnancy appear to be affected in minimal ways and function relatively well within society. We questioned whether this effect of prenatal alcohol in the adult is generally minimal. To bear on this, we determined whether we could distinguish alcohol-exposed from nonexposed individuals in a population of male veterans, selected because of both their accepted level of function within society (e.g., honorable discharge from the military) and their admission to an alcohol treatment unit (thus, a greater likelihood of parental alcoholism, because of its familial aggregation). Consecutively admitted alcoholics (cases; n = 77) with likely maternal alcohol ingestion during their pregnancy or the first 10 years of life were matched with alcoholics with no maternal alcohol exposure during these periods (controls; n = 161). Each subject completed questionnaires regarding personal birthweight, alcohol, drug, educational and work histories, and family (including parental) alcohol and drug histories. We measured height, weight, and head circumference; checked for facial and hand anomalies; and took a frontal facial photograph, from which measurements of features were made. Data were analyzed by univariate statistics and stepwise logistic regression. No case had bona fide fetal alcohol syndrome. With univariate statistical analyses, the cases differed from the controls in 10 variables, including duration of drinking, width of alae nasae, being hyperactive or having a short attention span, and being small at birth. By stepwise logistic regression, the variables marital status, small size at birth, duration of drinking, and the presence of a smooth philtrum were marginally (the first two) or definitely (the last two) significant predictors of case status. Analysis of only the 37 cases in whom maternal prenatal drinking was

Alcoholic neuropathy

MedlinePlus

Neuropathy - alcoholic; Alcoholic polyneuropathy ... The exact cause of alcoholic neuropathy is unknown. It likely includes both a direct poisoning of the nerve by the alcohol and the effect of poor nutrition ...

The economics of alcohol abuse and alcohol-control policies.

PubMed

Cook, Philip J; Moore, Michael J

2002-01-01

Economic research has contributed to the evaluation of alcohol policy through empirical analysis of the effects of alcohol-control measures on alcohol consumption and its consequences. It has also provided an accounting framework for defining and comparing costs and benefits of alcohol consumption and related policy interventions, including excise taxes. The most important finding from the economics literature is that consumers tend to drink less ethanol, and have fewer alcohol-related problems, when alcoholic beverage prices are increased or alcohol availability is restricted. That set of findings is relevant for policy purposes because alcohol abuse imposes large "external" costs on others. Important challenges remain, including developing a better understanding of the effects of drinking on labor-market productivity.

The economic impact of alcohol abuse and alcoholism.

PubMed Central

Burke, T R

1988-01-01

The economic effects of alcohol abuse are as damaging to the nation as the health effects, affecting the family, the community, and persons of all ages. Underaged drinking is interfering with children's development, affecting the nation's ability to respond to economic challenge in the future. The college aged may be the most difficult to educate about alcohol abuse because of drinking patterns established at an early age and susceptibility to advertising inducements. Health care costs for families with an alcoholic member are twice those for families without one, and up to half of all emergency room admissions are alcohol related. Fetal alcohol syndrome is one of the top three known causes of birth defects, and is totally preventable. Alcohol abuse and alcoholism are estimated to have cost the nation $117 billion in 1983, while nonalcoholic drug abuse that year cost $60 billion. Costs of alcohol abuse are expected to be $136 billion a year by 1990, mostly from lost productivity and employment. Between 6 and 7 million workers are alcoholic, with an undetermined loss of productivity, profits, and competitiveness of American business. Alcohol abuse contributes to the high health care costs of the elderly beneficiaries of Federal health financing programs. Heavily affected minorities include blacks, Hispanics, and Native Americans. Society tends to treat the medical and social consequences of alcohol abuse, rather than its causes. Although our experience with the consequences of alcohol abuse is greater than that for any other drug, public concern for its prevention and treatment is less than for other major illnesses or abuse of other drugs.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:3141948

Parental History of Anxiety and Alcohol-Use Disorders and Alcohol Expectancies as Predictors of Alcohol-Related Problems*

PubMed Central

Morean, Meghan E.; Corbin, William R.; Sinha, Rajita; O'Malley, Stephanie S.

2009-01-01

Objective: Research has consistently identified a family history of alcoholism as a risk factor for alcohol-related problems, and global positive expectancies have been found to moderate this association. High rates of comorbidity between alcohol use and anxiety disorders suggest that a family history of anxiety disorders may also increase risk. Further, expectations of negative reinforcement (e.g., tension reduction) have been found to moderate the influence of anxiety-related traits. The current study sought to extend previous research by examining the influence of parental history of alcoholism, anxiety disorders, and the combination, as predictors of alcohol-related problems. Expectancies of global positive changes and tension reduction were hypothesized to moderate the influence of parental history of alcoholism and anxiety, respectively. Method: Direct interviews with parents assessed their history of alcoholism and anxiety for 144 offspring (ages 18-32; 53.5% male) creating four groups: those with a parental history of alcoholism (27.80%), anxiety (22.20%), both alcoholism and anxiety (33.30%), and no history of psychopathology (16.70%). Established measures assessed the offsprings'alcohol expectancies, alcohol use, and alcohol-related problems. Results: Although expected interactions between parental alcoholism and global positive expectancies and between parental anxiety and tension-reduction expectancies were not found, global positive expectancies were associated with alcohol-related problems among the group with parental history of both alcoholism and anxiety. Conclusions: The results suggest that the relation between parental history of alcoholism and global positive expectancies observed in previous studies may be strongest among individuals with a comorbid parental history of alcohol and anxiety disorders. Incorporating expectancies into interventions targeting individuals with a comorbid parental history of alcohol and anxiety disorders may have

Acute Alcohol Consumption, Alcohol Outlets, and Gun Suicide

PubMed Central

Branas, Charles C.; Richmond, Therese S.; Ten Have, Thomas R.; Wiebe, Douglas J.

2014-01-01

A case–control study of 149 intentionally self-inflicted gun injury cases (including completed gun suicides) and 302 population-based controls was conducted from 2003 to 2006 in a major US city. Two focal independent variables, acute alcohol consumption and alcohol outlet availability, were measured. Conditional logistic regression was adjusted for confounding variables. Gun suicide risk to individuals in areas of high alcohol outlet availability was less than the gun suicide risk they incurred from acute alcohol consumption, especially to excess. This corroborates prior work but also uncovers new information about the relationships between acute alcohol consumption, alcohol outlets, and gun suicide. Study limitations and implications are discussed. PMID:21929327

Acute alcohol consumption, alcohol outlets, and gun suicide.

PubMed

Branas, Charles C; Richmond, Therese S; Ten Have, Thomas R; Wiebe, Douglas J

2011-01-01

A case-control study of 149 intentionally self-inflicted gun injury cases (including completed gun suicides) and 302 population-based controls was conducted from 2003 to 2006 in a major US city. Two focal independent variables, acute alcohol consumption and alcohol outlet availability, were measured. Conditional logistic regression was adjusted for confounding variables. Gun suicide risk to individuals in areas of high alcohol outlet availability was less than the gun suicide risk they incurred from acute alcohol consumption, especially to excess. This corroborates prior work but also uncovers new information about the relationships between acute alcohol consumption, alcohol outlets, and gun suicide. Study limitations and implications are discussed.

Exposure to alcohol advertisements and teenage alcohol-related problems.

PubMed

Grenard, Jerry L; Dent, Clyde W; Stacy, Alan W

2013-02-01

This study used prospective data to test the hypothesis that exposure to alcohol advertising contributes to an increase in underage drinking and that an increase in underage drinking then leads to problems associated with drinking alcohol. A total of 3890 students were surveyed once per year across 4 years from the 7th through the 10th grades. Assessments included several measures of exposure to alcohol advertising, alcohol use, problems related to alcohol use, and a range of covariates, such as age, drinking by peers, drinking by close adults, playing sports, general TV watching, acculturation, parents' jobs, and parents' education. Structural equation modeling of alcohol consumption showed that exposure to alcohol ads and/or liking of those ads in seventh grade were predictive of the latent growth factors for alcohol use (past 30 days and past 6 months) after controlling for covariates. In addition, there was a significant total effect for boys and a significant mediated effect for girls of exposure to alcohol ads and liking of those ads in 7th grade through latent growth factors for alcohol use on alcohol-related problems in 10th grade. Younger adolescents appear to be susceptible to the persuasive messages contained in alcohol commercials broadcast on TV, which sometimes results in a positive affective reaction to the ads. Alcohol ad exposure and the affective reaction to those ads influence some youth to drink more and experience drinking-related problems later in adolescence.

Exposure to Alcohol Advertisements and Teenage Alcohol-Related Problems

PubMed Central

Dent, Clyde W.; Stacy, Alan W.

2013-01-01

OBJECTIVE: This study used prospective data to test the hypothesis that exposure to alcohol advertising contributes to an increase in underage drinking and that an increase in underage drinking then leads to problems associated with drinking alcohol. METHODS: A total of 3890 students were surveyed once per year across 4 years from the 7th through the 10th grades. Assessments included several measures of exposure to alcohol advertising, alcohol use, problems related to alcohol use, and a range of covariates, such as age, drinking by peers, drinking by close adults, playing sports, general TV watching, acculturation, parents’ jobs, and parents’ education. RESULTS: Structural equation modeling of alcohol consumption showed that exposure to alcohol ads and/or liking of those ads in seventh grade were predictive of the latent growth factors for alcohol use (past 30 days and past 6 months) after controlling for covariates. In addition, there was a significant total effect for boys and a significant mediated effect for girls of exposure to alcohol ads and liking of those ads in 7th grade through latent growth factors for alcohol use on alcohol-related problems in 10th grade. CONCLUSIONS: Younger adolescents appear to be susceptible to the persuasive messages contained in alcohol commercials broadcast on TV, which sometimes results in a positive affective reaction to the ads. Alcohol ad exposure and the affective reaction to those ads influence some youth to drink more and experience drinking-related problems later in adolescence. PMID:23359585

75 FR 78228 - Takes of Marine Mammals Incidental to Specified Activities; Columbia River Crossing Project...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-12-15

... (Zalophus californianus), and harbor seals (Phoca vitulina). Specified Activities CRC is proposing a...-water bents, consisting of one to three drilled shafts. The permanent in-water piers of both the Columbia River and North Portland Harbor crossings will be constructed using drilled shafts, rather than...

Alcohol use in films and adolescent alcohol use.

PubMed

Waylen, Andrea; Leary, Sam; Ness, Andrew; Sargent, James

2015-05-01

To investigate whether exposure to alcohol use in films (AUFs) is associated with early alcohol use, binge drinking, and alcohol-related problems in British adolescents. Cross-sectional study with 5163 15-year-olds from the Avon Longitudinal Study of Parents and Children in the United Kingdom. We measured adolescent exposure to AUFs, age at onset of alcohol use, and binge-drinking behavior. We adjusted for early childhood social, family and behavioral factors, adolescent tobacco use, and peer drinking. After adjustment, adolescents with the highest exposure to AUFs were 1.2 (95% confidence interval [CI]: 1.1-1.3) times more likely to have tried alcohol compared with those least exposed and 1.7 (95% CI: 1.5-2.0) times more likely to binge drink. They were 2.4 (95% CI: 1.9-3.1) times more likely to drink weekly and 2.0 (95% CI: 1.7-2.4) times more likely to have alcohol-related problems than those least exposed. Exposure to AUFs is associated with higher risk of alcohol use and alcohol-related problems in UK adolescents. Our findings provide evidence to support the argument that a review of film-rating categories and alcohol ratings for all films may help reduce problem-related alcohol consumption in young people. Copyright © 2015 by the American Academy of Pediatrics.

Impulsivity Moderates Subjective Responses to Alcohol in Alcohol-Dependent Individuals.

PubMed

Westman, Jonathan G; Bujarski, Spencer; Ray, Lara A

2017-03-09

Studies of social drinkers indicate that subjective response (SR) to alcohol and impulsivity are risk factors for the development of alcohol use disorder which may be related. It is unclear, however, whether there are significant relationships between SR and impulsivity among individuals with alcohol dependence. Using data from an intravenous (IV) alcohol challenge study, the present study is the first to explore the relationship between impulsivity and SR during alcohol administration among alcohol-dependent individuals. Non-treatment-seeking, alcohol-dependent individuals (N = 42) completed the Delay Discounting Task to measure impulsivity and then completed two counterbalanced, placebo-controlled IV alcohol administration sessions, which included assessments of SR at breath alcohol concentration (BrAC) levels of 0.00, 0.02, 0.04 and 0.06 g/dl. Analyses revealed that more impulsive participants experienced higher subjective stimulation and positive mood in response to rising BrACs as compared to less impulsive individuals. More impulsive participants also experienced increased sedation over time regardless of condition (i.e. alcohol vs. saline). These findings suggest that among alcohol-dependent individuals, impulsivity is positively associated with the hedonic effects of alcohol as compared to placebo. High impulsivity may characterize a subset of alcohol-dependent individuals who drink to experience the rewarding effects of alcohol. © The Author 2016. Medical Council on Alcohol and Oxford University Press. All rights reserved.

Alcoholic cardiomyopathy

PubMed Central

Guzzo-Merello, Gonzalo; Cobo-Marcos, Marta; Gallego-Delgado, Maria; Garcia-Pavia, Pablo

2014-01-01

Alcohol is the most frequently consumed toxic substance in the world. Low to moderate daily intake of alcohol has been shown to have beneficial effects on the cardiovascular system. In contrast, exposure to high levels of alcohol for a long period could lead to progressive cardiac dysfunction and heart failure. Cardiac dysfunction associated with chronic and excessive alcohol intake is a specific cardiac disease known as alcoholic cardiomyopathy (ACM). In spite of its clinical importance, data on ACM and how alcohol damages the heart are limited. In this review, we evaluate available evidence linking excessive alcohol consumption with heart failure and dilated cardiomyopathy. Additionally, we discuss the clinical presentation, prognosis and treatment of ACM. PMID:25228956

Alcohol, Diet and Drug Use Preceding Alcoholic Hepatitis.

PubMed

Parker, Richard; Neuberger, James M

2018-05-31

Alcoholic hepatitis (AH) is a severe manifestation of alcohol-related liver disease characterised by jaundice and liver failure. It is not known what might trigger an episode of AH. We interviewed patients to investigate changes in behaviour before the onset of AH. Structured interviews were performed with patients with AH to examine their alcohol use, diet, drug use and smoking habit. Clinical and laboratory results were noted. Patients were followed up for 12 months after interview. Data from 39 patients was analysed. No single behavioural change occurred before the onset of jaundice, although reductions in alcohol and/or dietary intake were common. Reduction in alcohol use was seen to occur approximately 14 days before the onset of jaundice. Increased alcohol intake was not common. Clinical and laboratory data varied between types of behaviour changes, although these were not statistically significant. No changes in drug use or tobacco were reported before AH. Those who had not reduced alcohol intake or had increased their drinking had better survival. No single type of behaviour change is associated with AH. Contrary to previous assertions, increased alcohol intake was not common; in fact, participants were much more likely to have reduced their alcohol intake. © 2018 S. Karger AG, Basel.

Nutritional evaluation of alcoholic inpatients admitted for alcohol detoxification.

PubMed

Teixeira, Joana; Mota, Teresa; Fernandes, João Cabral

2011-01-01

To assess nutritional risk of alcoholic patients admitted for alcohol detoxification. Screening of nutritional risk of alcoholic patients using the Malnutrition Universal Screening Tool. Fifty-three percentage patients at presentation were rated as being at medium or high risk of malnutrition. Malnutrition should be actively considered and screened for in alcoholic patients admitted for alcohol detoxification due to its high prevalence and benefits obtained from treatment.

Black Alcoholism.

ERIC Educational Resources Information Center

Watts, Thomas D.; Wright, Roosevelt

1988-01-01

Examines some aspects of the problem of alcoholism among Blacks, asserting that Black alcoholism can best be considered in an ecological, environmental, sociocultural, and public health context. Notes need for further research on alcoholism among Blacks and for action to reduce the problem of Black alcoholism. (NB)

Alcohol attentional bias is associated with autonomic indices of stress-primed alcohol cue-reactivity in alcohol-dependent patients.

PubMed

Garland, Eric L; Franken, Ingmar H; Sheetz, John J; Howard, Matthew O

2012-06-01

When alcohol-dependent individuals are exposed to drinking-related cues, they exhibit psychophysiological reactivity such as changes in heart rate variability (HRV) and skin temperature. Moreover, such alcohol cue-reactivity may co-occur with attentional bias (AB) toward alcohol cues. In turn, stress may promote appetitive responses by exacerbating these autonomic and attentional factors. Although cue-reactivity paradigms have been used for decades to probe such automatic appetitive processes in persons with alcohol-use disorders, less is known about the attentional correlates of alcohol cue-reactivity. In this study, alcohol-dependent adults (N = 58) recruited from a residential treatment facility completed a spatial cueing task as a measure of alcohol AB and affect-modulated cue-reactivity protocol. Multiple linear regression analyses revealed that alcohol AB was significantly positively associated with parasympathetically mediated HRV and finger temperature slope and inversely associated with sympathetically mediated HRV during stress-primed alcohol cue-exposure, independent of alcohol dependence severity, time in treatment, alcohol craving, and perceived stress. Study findings suggest that alcohol AB is linked with physiological cue-reactivity and that different attentional strategies are associated with distinct profiles of autonomic responses that may ultimately index or confer additional risk for alcohol dependence.

Exposure to Televised Alcohol Ads and Subsequent Adolescent Alcohol Use

ERIC Educational Resources Information Center

Stacy, Alan W.; Zogg, Jennifer B.; Unger, Jennifer B.; Dent, Clyde W.

2004-01-01

Objective : To assess the impact of televised alcohol commercials on adolescents' alcohol use. Methods : Adolescents completed questionnaires about alcohol commercials and alcohol use in a prospective study. Results : A one standard deviation increase in viewing television programs containing alcohol commercials in seventh grade was associated…

A Lipolytic Lecithin:Cholesterol Acyltransferase Secreted by Toxoplasma Facilitates Parasite Replication and Egress*

PubMed Central

Pszenny, Viviana; Ehrenman, Karen; Romano, Julia D.; Kennard, Andrea; Schultz, Aric; Roos, David S.; Grigg, Michael E.; Carruthers, Vern B.; Coppens, Isabelle

2016-01-01

The protozoan parasite Toxoplasma gondii develops within a parasitophorous vacuole (PV) in mammalian cells, where it scavenges cholesterol. When cholesterol is present in excess in its environment, the parasite expulses this lipid into the PV or esterifies it for storage in lipid bodies. Here, we characterized a unique T. gondii homologue of mammalian lecithin:cholesterol acyltransferase (LCAT), a key enzyme that produces cholesteryl esters via transfer of acyl groups from phospholipids to the 3-OH of free cholesterol, leading to the removal of excess cholesterol from tissues. TgLCAT contains a motif characteristic of serine lipases “AHSLG” and the catalytic triad consisting of serine, aspartate, and histidine (SDH) from LCAT enzymes. TgLCAT is secreted by the parasite, but unlike other LCAT enzymes it is cleaved into two proteolytic fragments that share the residues of the catalytic triad and need to be reassembled to reconstitute enzymatic activity. TgLCAT uses phosphatidylcholine as substrate to form lysophosphatidylcholine that has the potential to disrupt membranes. The released fatty acid is transferred to cholesterol, but with a lower transesterification activity than mammalian LCAT. TgLCAT is stored in a subpopulation of dense granule secretory organelles, and following secretion, it localizes to the PV and parasite plasma membrane. LCAT-null parasites have impaired growth in vitro, reduced virulence in animals, and exhibit delays in egress from host cells. Parasites overexpressing LCAT show increased virulence and faster egress. These observations demonstrate that TgLCAT influences the outcome of an infection, presumably by facilitating replication and egress depending on the developmental stage of the parasite. PMID:26694607

American Alcohol Photo Stimuli (AAPS): A standardized set of alcohol and matched non-alcohol images.

PubMed

Stauffer, Christopher S; Dobberteen, Lily; Woolley, Joshua D

2017-11-01

Photographic stimuli are commonly used to assess cue reactivity in the research and treatment of alcohol use disorder. The stimuli used are often non-standardized, not properly validated, and poorly controlled. There are no previously published, validated, American-relevant sets of alcohol images created in a standardized fashion. We aimed to: 1) make available a standardized, matched set of photographic alcohol and non-alcohol beverage stimuli, 2) establish face validity, the extent to which the stimuli are subjectively viewed as what they are purported to be, and 3) establish construct validity, the degree to which a test measures what it claims to be measuring. We produced a standardized set of 36 images consisting of American alcohol and non-alcohol beverages matched for basic color, form, and complexity. A total of 178 participants (95 male, 82 female, 1 genderqueer) rated each image for appetitiveness. An arrow-probe task, in which matched pairs were categorized after being presented for 200 ms, assessed face validity. Criteria for construct validity were met if variation in AUDIT scores were associated with variation in performance on tasks during alcohol image presentation. Overall, images were categorized with >90% accuracy. Participants' AUDIT scores correlated significantly with alcohol "want" and "like" ratings [r(176) = 0.27, p = <0.001; r(176) = 0.36, p = <0.001] and arrow-probe latency [r(176) = -0.22, p = 0.004], but not with non-alcohol outcomes. Furthermore, appetitive ratings and arrow-probe latency for alcohol, but not non-alcohol, differed significantly for heavy versus light drinkers. Our image set provides valid and reliable alcohol stimuli for both explicit and implicit tests of cue reactivity. The use of standardized, validated, reliable image sets may improve consistency across research and treatment paradigms.

Comparing Alcohol Marketing and Alcohol Warning Message Policies Across Canada.

PubMed

Wettlaufer, Ashley; Cukier, Samantha N; Giesbrecht, Norman

2017-08-24

In order to reduce harms from alcohol, evidence-based policies are to be introduced and sustained. To facilitate the dissemination of policies that reduce alcohol-related harms by documenting, comparing, and sharing information on effective alcohol polices related to restrictions on alcohol marketing and alcohol warning messaging in 10 Canadian provinces. Team members developed measurable indicators to assess policies on (a) restrictions on alcohol marketing, and (b) alcohol warning messaging. Indicators were peer-reviewed by three alcohol policy experts, refined, and data were collected, submitted for validation by provincial experts, and scored independently by two team members. The national average score was 52% for restrictions on marketing policies and 18% for alcohol warning message policies. Most provinces had marketing regulations that went beyond the federal guidelines with penalties for violating marketing regulations. The provincial liquor boards' web pages focused on product promotion, and there were few restrictions on sponsorship activities. No province has implemented alcohol warning labels, and Ontario was the sole province to have legislated warning signs at all points-of-sale. Most provinces provided a variety of warning signs to be displayed voluntarily at points-of-sale; however, the quality of messages varied. Conclusions/Importance: There is extensive alcohol marketing with comparatively few messages focused on the potential harms associated with alcohol. It is recommended that governments collaborate with multiple stakeholders to maximize the preventive impact of restrictions on alcohol marketing and advertising, and a broader implementation of alcohol warning messages.

Alcohol and pregnancy

MedlinePlus

Drinking alcohol during pregnancy; Fetal alcohol syndrome - pregnancy; FAS - fetal alcohol syndrome ... lead to lifelong damage. DANGERS OF ALCOHOL DURING PREGNANCY Drinking a lot of alcohol during pregnancy can ...

The role of lecithin cholesterol acyltransferase and organic substances from coal in the etiology of Balkan endemic nephropathy: A new hypothesis

USGS Publications Warehouse

Pavlovic, N.M.; Orem, W.H.; Tatu, C.A.; Lerch, H.E.; Bunnell, J.E.; Feder, G.L.; Kostic, E.N.; Ordodi, V.L.

2008-01-01

Balkan endemic nephropathy (BEN) occurs in Serbia, Bulgaria, Romania, Bosnia and Herzegovina, and Croatia. BEN has been characterized as a chronic, slowly progressive renal disease of unknown etiology. In this study, we examined the influence of soluble organic compounds in drinking water leached from Pliocene lignite from BEN-endemic areas on plasma lecithin-cholesterol acyltransferase (LCAT) activity. We found that changes for all samples were the most prominent for the dilution category containing 90% plasma and 10% of diluting media. Water samples from BEN villages from Serbia and Romania showed higher LCAT inhibiting activity (p = 0.02) and (p = 0.003), respectively, compared to deionised water and non-endemic water. A secondary LCAT deficiency could result from this inhibitory effect of the organic compounds found in endemic water supplies and provide an ethiopathogenic basis for the development of BEN in the susceptible population. ?? 2007 Elsevier Ltd. All rights reserved.

Discovery of a potent and orally available acyl-CoA: cholesterol acyltransferase inhibitor as an anti-atherosclerotic agent: (4-phenylcoumarin)acetanilide derivatives.

PubMed

Ogino, Masaki; Fukui, Seiji; Nakada, Yoshihisa; Tokunoh, Ryosuke; Itokawa, Shigekazu; Kakoi, Yuichi; Nishimura, Satoshi; Sanada, Tsukasa; Fuse, Hiromitsu; Kubo, Kazuki; Wada, Takeo; Marui, Shogo

2011-01-01

Acyl-CoA: cholesterol acyltransferase (ACAT) is an intracellular enzyme that catalyzes cholesterol esterification. ACAT inhibitors are expected to be potent therapeutic agents for the treatment of atherosclerosis. A series of potent ACAT inhibitors based on an (4-phenylcoumarin)acetanilide scaffold was identified. Evaluation of the structure-activity relationships of a substituent on this scaffold, with an emphasis on improving the pharmacokinetic profile led to the discovery of 2-[7-chloro-4-(3-chlorophenyl)-6-methyl-2-oxo-2H-chromen-3-yl]-N-[4-chloro-2-(trifluoromethyl)phenyl]acetamide (23), which exhibited potent ACAT inhibitory activity (IC50=12 nM) and good pharmacokinetic profile in mice. Compound 23 also showed regressive effects on atherosclerotic plaques in apolipoprotein (apo)E knock out (KO) mice at a dose of 0.3 mg/kg per os (p.o.).

[Early alcohol initiation and increased adult alcohol consumption: cause or indicator?].

PubMed

Geels, L M; Vink, J M; van Beek, J H D A; Willemsen, G; Bartels, M; Boomsma, D I

2013-01-01

Early alcohol initiation is strongly associated with increased alcohol consumption and alcohol abuse/dependence in adulthood. The mechanisms that underlie this association are unclear. To examine whether there is a causal link between early alcohol initiation and later alcohol consumption. Survey data were collected from twin pairs (age range 18-80) included in the Netherlands Twin Register (NTR). A discordant twin design was used to examine the origin of the link between early alcohol initiation and adult alcohol consumption. Within monozygotic pairs (82-143 pairs), twins who started drinking early were compared to their brother/sister who started drinking later, on frequency of alcohol use, weekly alcohol consumption, number of alcohol intoxications, excessive drinking, alcohol abuse/-dependence, and hazardous drinking. By drawing comparisons within monozygotic pairs, we were able to control for the effects of genes/shared environment. Additional analyses examined the effects of age, sex, and in-/exclusion of lifelong abstainers. Within monozygotic twin pairs, the twin who had started drinking early did not differ significantly from his/her brother/sister with respect to future alcohol consumption. Results were independent of age, sex, and in-/exclusion of lifelong abstainers. Early alcohol initiation did not have significant causal effects on subsequent alcohol consumption in adulthood and may be an indicator of a predisposition for alcohol consumption. Campaigns aimed at raising the minimum age for alcohol initiation will possibly have only a limited effect on adult alcohol consumption.

Final report of the safety assessment of Alcohol Denat., including SD Alcohol 3-A, SD Alcohol 30, SD Alcohol 39, SD Alcohol 39-B, SD Alcohol 39-C, SD Alcohol 40, SD Alcohol 40-B, and SD Alcohol 40-C, and the denaturants, Quassin, Brucine Sulfate/Brucine, and Denatonium Benzoate.

PubMed

2008-01-01

Alcohol Denat. is the generic term used by the cosmetics industry to describe denatured alcohol. Alcohol Denat. and various specially denatured (SD) alcohols are used as cosmetic ingredients in a wide variety of products. Many denaturants have been previously considered, on an individual basis, as cosmetic ingredients by the Cosmetic Ingredient Review (CIR) Expert Panel, whereas others, including Brucine and Brucine Sulfate, Denatonium Benzoate, and Quassin, have not previously been evaluated. Quassin is a bitter alkaloid obtained from the wood of Quassia amara. Quassin has been used as an insect antifeedant and insecticide and several studies demonstrate its effectiveness. At oral doses up to 1000 mg/kg using rats, Quassin was not toxic in acute and short-term tests, but some reversible piloerection, decrease in motor activity, and a partial loss of righting reflex were found in mice at 500 mg/kg. At 1000 mg/kg given intraperitoneally (i.p.), all mice died within 24 h of receiving treatment. In a cytotoxicity test with brine shrimp, 1 mg/ml of Quassin did not possess any cytotoxic or antiplasmodial activity. Quassin administered to rat Leydig cells in vitro at concentrations of 5-25 ng/ml inhibited both the basal and luteinizing hormone (LH)-stimulated testosterone secretion in a dose-related fashion. Quassin at doses up to 2.0 g/kg in drinking water using rats produced no significant effect on the body weights, but the mean weights of the testes, seminal vesicles, and epididymides were significantly reduced, and the weights of the anterior pituitary glands were significantly increased. The sperm counts and levels of LH, follicle-stimulating hormone (FSH), and testosterone were significantly lower in groups treated with Quassin. Brucine is a derivative of 2-hydroxystrychnine. Swiss-Webster mice given Brucine base, 30 ml/kg, had an acute oral LD(50) of 150 mg/kg, with central nervous system depression followed by convulsions and seizures in some cases. In those

Discovery of a new mechanism for regulation of plant triacylglycerol metabolism: The peanut diacylglycerol acyltransferase-1 gene family transcriptome is highly enriched in alternative splicing variants.

PubMed

Zheng, Ling; Shockey, Jay; Guo, Feng; Shi, Lingmin; Li, Xinguo; Shan, Lei; Wan, Shubo; Peng, Zhenying

2017-12-01

Triacylglycerols (TAGs) are the most important energy storage form in oilseed crops. Diacylglycerol acyltransferase (DGAT) catalyzes the rate-limiting step of the Kennedy pathway of TAG biosynthesis. To date, little is known about the regulation of DGAT activity in peanut (Arachis hypogaea), an agronomically important oilseed crop that is cultivated in many parts of the world. In this study, seven distinct forms of type 1 DGAT (AhDGAT1.1-AhDGAT1.7) were identified, cloned, and characterized. Comparisons of the nucleotide sequences and gene structures revealed many different splicing variants of AhDGAT1, some of which displayed different organ-specific expression patterns. A representative gene (AhDGAT1.1) was transformed into wild-type tobacco and was shown to increase seed fatty acid (FA) content by 14.7%-20.9%. All seven AhDGAT1s were expressed in TAG-deficient Saccharomyces cerevisiae strain H1246; the five longest AhDGAT1 variants generated high levels of acyltransferase activity and complemented the free fatty acid lethality phenotype in this strain. The alternative splicing that gives rise to AhDGAT1.2 and AhDGAT1.4 creates predicted protein C-terminal truncations. The proteins encoded by these two variants were not active and did not complement the fatty acid sensitivity in H1246. These results were verified by visualization of intracellular lipid droplets using Nile Red staining. Collectively, the results presented here represent the first comprehensive analysis of the peanut DGAT1 gene family, which, unlike in other published plant DGAT1 sequences, shows widespread alternative splicing that may affect the expression patterns and enzyme activities of some members of the gene family. Copyright © 2017. Published by Elsevier GmbH.

Alcohol Energy Drinks

MedlinePlus

... Home / About Addiction / Alcohol / Alcohol Energy Drinks Alcohol Energy Drinks Read 34001 times font size decrease font size increase font size Print Email Alcohol energy drinks (AEDs) or Caffeinated alcoholic beverages (CABs) are ...

Alcohol industry and non-alcohol industry sponsorship of sportspeople and drinking.

PubMed

O'Brien, Kerry S; Miller, Peter G; Kolt, Gregory S; Martens, Matthew P; Webber, Andrew

2011-01-01

To examine the relationship between direct alcohol and non-alcohol sponsorship and drinking in Australian sportspeople. Australian sportspeople (N = 652; 51% female) completed questionnaires on alcohol and non-alcohol industry sponsorship (from bars, cafes etc.), drinking behaviour (Alcohol Use Disorders Identification Test (AUDIT)) and known confounders. 31% reported sponsorship (29.8% alcohol industry; 3.7% both alcohol and non-alcohol industry and 1.5% non-alcohol industry only) Multivariate regression showed that receipt of alcohol industry sponsorship was predictive of higher AUDIT scores (β(adj) = 1.67, 95% confidence interval (CI): 0.56-2.78), but non-alcohol industry sponsorship and combinations of both were not (β(adj) = 0.18, 95% CI: -2.61 to 2.68; and β(adj) = 2.58, 95% CI: -0.60 to 5.76, respectively). Governments should consider alternatives to alcohol industry sponsorship of sport. Hypothecated taxes on tobacco have been used successfully for replacing tobacco sponsorship of sport in some countries, and may show equal utility for the alcohol industry's funding of sport.

Avoidance of alcohol-related stimuli in alcohol-dependent inpatients.

PubMed

Townshend, J M; Duka, T

2007-08-01

Previous research has shown an attentional bias toward drug-related stimuli in heavy social drinkers. Attentional orientation to drug-related cues may lead to increased craving and preoccupation with the drug and impaired ability to focus attention on nondrug-related activities, resulting in renewed drug taking or relapse from drug abstinence. The aim of this study was to investigate whether alcohol-dependent inpatients would differ in their selective attention toward alcohol-related stimuli in comparison with a group of social drinking controls. Thirty-five alcohol-dependent inpatients were compared with a group of 39 social drinking controls matched for age, sex, and verbal IQ. Attentional bias was assessed using alcohol-related pictures in a dot probe detection task. Questionnaires were used to examine outcome expectancies after alcohol consumption, anxiety, mood, and craving. The alcoholic inpatients showed a bias away from the alcohol-related stimuli, scored higher on alcohol outcome expectancies, and on anxiety measures (both state and trait). They also presented with more negative mood compared with the control group. Craving was higher in the alcoholic group for the factor "loss of control over drinking." Alcoholic inpatients undergoing treatment based on the 12-step treatment of Alcoholics Anonymous (Minnesota model), which includes counseling, and intensive group, individual, and family psychotherapy, show an avoidance for drug-related stimuli and a perception of loss of control over drinking. We suggest that their increased perception of loss of control over drinking produces the avoidance from the drug-related stimuli.

Glycerol-3-phosphate O-acyltransferase is required for PBAN-induced sex pheromone biosynthesis in Bombyx mori

PubMed Central

Du, Mengfang; Liu, Xiaoguang; Liu, Xiaoming; Yin, Xinming; Han, Shuangyin; Song, Qisheng; An, Shiheng

2015-01-01

Female moths employ their own pheromone blends as a communicational medium in mating behavior. The biosynthesis and release of sex pheromone in female moths are regulated by pheromone biosynthesis activating neuropeptide (PBAN) and the corresponding action of PBAN has been well elucidated in Bombyx mori. However, very little is known about the molecular mechanism regarding the biosynthesis of sex pheromone precursor. In this study, quantitative proteomics was utilized to comprehensively elucidate the expression dynamics of pheromone glands (PGs) during development. Proteomic analysis revealed a serial of differentially expressed sex pheromone biosynthesis-associated proteins at the different time points of B. mori development. Most interestingly B. mori glycerol-3-phosphate O-acyltransferase (BmGPAT) was found to be expressed during the key periods of sex pheromone biosynthesis. RNAi knockdown of BmGPAT confirmed the important function of this protein in the biosynthesis of sex pheromone precursor, triacylglcerol (TAG), and subsequently PBAN-induced production of sex pheromone, bombykol. Behavioral analysis showed that RNAi knockdown of GPAT significantly impaired the ability of females to attract males. Our findings indicate that GPAT acts to regulate the biosynthesis of sex pheromone precursor, TAG, thus influencing PBAN-induced sex pheromone production and subsequent mating behavior. PMID:25630665

Cloning, heterologous expression and biochemical characterization of plastidial sn-glycerol-3-phosphate acyltransferase from Helianthus annuus.

PubMed

Payá-Milans, Miriam; Venegas-Calerón, Mónica; Salas, Joaquín J; Garcés, Rafael; Martínez-Force, Enrique

2015-03-01

The acyl-[acyl carrier protein]:sn-1-glycerol-3-phosphate acyltransferase (GPAT; E.C. 2.3.1.15) catalyzes the first step of glycerolipid assembly within the stroma of the chloroplast. In the present study, the sunflower (Helianthus annuus, L.) stromal GPAT was cloned, sequenced and characterized. We identified a single ORF of 1344base pairs that encoded a GPAT sharing strong sequence homology with the plastidial GPAT from Arabidopsis thaliana (ATS1, At1g32200). Gene expression studies showed that the highest transcript levels occurred in green tissues in which chloroplasts are abundant. The corresponding mature protein was heterologously overexpressed in Escherichia coli for purification and biochemical characterization. In vitro assays using radiolabelled acyl-ACPs and glycerol-3-phosphate as substrates revealed a strong preference for oleic versus palmitic acid, and weak activity towards stearic acid. The positional fatty acid composition of relevant chloroplast phospholipids from sunflower leaves did not reflect the in vitro GPAT specificity, suggesting a more complex scenario with mixed substrates at different concentrations, competition with other acyl-ACP consuming enzymatic reactions, etc. In summary, this study has confirmed the affinity of this enzyme which would partly explain the resistance to cold temperatures observed in sunflower plants. Copyright © 2015 Elsevier Ltd. All rights reserved.

Abrogating Monoacylglycerol Acyltransferase Activity in Liver Improves Glucose Tolerance and Hepatic Insulin Signaling in Obese Mice

PubMed Central

Soufi, Nisreen; Chambers, Kari T.; Chen, Zhouji; Schweitzer, George G.; McCommis, Kyle S.; Erion, Derek M.; Graham, Mark J.; Su, Xiong; Finck, Brian N.

2014-01-01

Monoacylglycerol acyltransferase (MGAT) enzymes convert monoacylglycerol to diacylglycerol (DAG), a lipid that has been linked to the development of hepatic insulin resistance through activation of protein kinase C (PKC). The expression of genes that encode MGAT enzymes is induced in the livers of insulin-resistant human subjects with nonalcoholic fatty liver disease, but whether MGAT activation is causal of hepatic steatosis or insulin resistance is unknown. We show that the expression of Mogat1, which encodes MGAT1, and MGAT activity are also increased in diet-induced obese (DIO) and ob/obmice. To probe the metabolic effects of MGAT1 in the livers of obese mice, we administered antisense oligonucleotides (ASOs) against Mogat1 to DIO and ob/ob mice for 3 weeks. Knockdown of Mogat1 in liver, which reduced hepatic MGAT activity, did not affect hepatic triacylglycerol content and unexpectedly increased total DAG content. Mogat1 inhibition also increased both membrane and cytosolic compartment DAG levels. However, Mogat1 ASO treatment significantly improved glucose tolerance and hepatic insulin signaling in obese mice. In summary, inactivation of hepatic MGAT activity, which is markedly increased in obese mice, improved glucose tolerance and hepatic insulin signaling independent of changes in body weight, intrahepatic DAG and TAG content, and PKC signaling. PMID:24595352

Genetics and alcoholism.

PubMed

Edenberg, Howard J; Foroud, Tatiana

2013-08-01

Alcohol is widely consumed; however, excessive use creates serious physical, psychological and social problems and contributes to the pathogenesis of many diseases. Alcohol use disorders (that is, alcohol dependence and alcohol abuse) are maladaptive patterns of excessive drinking that lead to serious problems. Abundant evidence indicates that alcohol dependence (alcoholism) is a complex genetic disease, with variations in a large number of genes affecting a person's risk of alcoholism. Some of these genes have been identified, including two genes involved in the metabolism of alcohol (ADH1B and ALDH2) that have the strongest known affects on the risk of alcoholism. Studies continue to reveal other genes in which variants affect the risk of alcoholism or related traits, including GABRA2, CHRM2, KCNJ6 and AUTS2. As more variants are analysed and studies are combined for meta-analysis to achieve increased sample sizes, an improved picture of the many genes and pathways that affect the risk of alcoholism will be possible.

Who 'likes' alcohol? Young Australians' engagement with alcohol marketing via social media and related alcohol consumption patterns.

PubMed

Carrotte, Elise R; Dietze, Paul M; Wright, Cassandra J; Lim, Megan S

2016-10-01

To describe patterns of 'liking' alcohol marketing social media pages, and determine related alcohol consumption patterns among young Australians. Participants were 1,001 Australians aged 15-29 years who completed a cross-sectional online survey. Logistic regression and ordinal logistic regression were used. A quarter (249/1001, 24.9%) liked at least one of the alcohol marketing social media pages, most commonly brands of spirits, cider and alcohol retailers. Underage participants were as likely as older participants to report liking these pages. Alcohol marketing social media use was significantly and independently associated with male gender, living outside a major city, ever using illegal drugs and early age of first alcohol consumption (all p<0.05). Alcohol marketing social media use (OR 2.1, 95% CI 1.5-2.8, p=<0.001) was independently associated with higher categories on the AUDIT-C, indicating riskier alcohol consumption. Liking or following alcohol marketing pages is common regardless of age, and associated with riskier alcohol consumption, among young Australians. There is a need to develop strategies to reduce the exposure to, and potential impact of, alcohol marketing social media pages on young Australians, and ensure these pages are neither accessible to nor targeting underage social media users. © 2016 Public Health Association of Australia.

[Alcohol and alcoholism among Brazilian adolescent public-school students].

PubMed

de Souza, Delma P Oliveira; Areco, Kelsy N; da Silveira Filho, Dartiu Xavier

2005-08-01

To estimate the prevalence of alcohol consumption and alcoholism among working and non-working adolescents. Cross-sectional study with a systematic, stratified sample 993 working adolescents and 1,725 non-working adolescents. The study included students enrolled in 1998 in the state public network schools of a city in Center-Western Brazil. An anonymous, self-administered questionnaire was completed by subjects in the classroom. Univariate and bivariate analyses and logistic regression were used. We found prevalences of 71.3% for alcohol consumption and 13.4% for alcoholism in the total sample, and higher prevalences among working students (81.0% and 14.9%) than among non-workers (65.8% and 12.6%). In addition to the association between alcohol use and work, we found both differences and similarities between the two groups. Alcoholism is not associated with work but is associated with male sex (OR=1.61; 95% CI: 1.18-2.19) and family history of alcohol use among both non-workers (OR=2.19; 95% CI: 1.60-2.99) and workers (OR=2.10; 95% CI: 1.42-3.12). The results of the present study indicate a high prevalence of alcohol consumption and alcoholism, which is higher among working adolescents. Sociodemographic, family, and work-related factors must be considered when attempting to implement educational measures aimed at changing alcohol-related behaviors in this population.

Alcohol and alcohol-related harm in China: policy changes needed

PubMed Central

Tang, Yi-lang; Xiang, Xiao-jun; Wang, Xu-yi; Cubells, Joseph F; Babor, Thomas F

2013-01-01

Abstract In China, alcohol consumption is increasing faster than anywhere else in the world. A steady increase in alcohol production has also been observed in the country, together with a rise in alcohol-related harm. Despite these trends, China’s policies on the sale and consumption of alcoholic beverages are weak compared with those of other countries in Asia. Weakest of all are its policies on taxation, drink driving laws, alcohol sale to minors and marketing licenses. The authors of this descriptive paper draw attention to the urgent need for public health professionals and government officials in China to prioritize population surveillance, research and interventions designed to reduce alcohol use disorders. They describe China’s current alcohol policies and recent trends in alcohol-related harm and highlight the need for health officials to conduct a thorough policy review from a public health perspective, using as a model the World Health Organization’s global strategy to reduce the harmful use of alcohol. PMID:23599550

[Nationwide survey of alcohol drinking and alcoholism among Japanese adults].

PubMed

Osaki, Yoneatsu; Matsushita, Sachio; Shirasaka, Tomonobu; Hiro, Hisanori; Higuchi, Susumu

2005-10-01

To investigate the characteristics of alcohol use among Japanese adults and prevalence of alcohol dependence in Japan, we conducted a nationwide survey on alcohol drinking behavior and alcohol dependence among Japanese adults using a representative sampling method. We sampled 3500 adults from throughout the entire country using a stratified random sampling method with two-step stratification, and carried out a home visit interview survey. A total of 2547 people (72.8%) responded to the survey. The survey period was June, 2003. The questionnaire contained questions about the frequency and quantity of alcohol use, 'hazardous use of alcohol' and 'alcohol dependence' according to the ICD-10 definition, several screening scales on problem use of alcohol (CAGE, KAST, AUDIT), life-time prevalence of 24 alcohol related diseases, smoking status, dysgryphia, and nightcap drinking. The number of respondents was, 1184 males, and 1363 females. Lifetime alcohol drinking, and weekly drinking, and daily drinking rates were 95.1%, 64.4%, and 36.2% for males, 79.0%, 27.5%, and 7.5% for females, respectively. Average daily alcohol consumption was 3.7 units for males, and 2.0 units for females (1 unit = 10 g pure alcohol). The proportion of drinkers who drank alcohol 4 units or more daily was 28.9% for males, and 7.6% for females, and that for 6 units or more was 12.7% for males, and 3.4% for females. The proportion of flasher was 41.2% for males, and 35.0% for females. Among screening questions, problem drinking was most frequently identified using AUDIT (score 12 points or more, 150 persons), followed by KAST (2 points or more, 100 persons) and CAGE (2 points or more, 98 persons). The number of subjects who met the ICD-10 criteria for alcohol dependence was 24, while the number who engaged in hazardous alcohol use was 64. This study revealed that problem drinking and alcohol dependence are a serious problem in Japanese general population. The problem of females drinking may be

Alcoholism and Suicide.

ERIC Educational Resources Information Center

Roy, Alec; Linnoila, Markku

1986-01-01

Reviews knowledge about suicide in alcoholism: how commonly suicide among alcoholics occurs; which alcoholics commit suicide and why; suicide among alcoholic women and alcoholic physicians; possible predisposing biological factors; possible linkages with depression, adverse life events, and personality disorder; and future research and directions.…

Parental Divorce, Maternal-Paternal Alcohol Problems, and Adult Offspring Lifetime Alcohol Dependence.

PubMed

Thompson, Ronald G; Alonzo, Dana; Hasin, Deborah S

2013-01-01

This study examined the influences of parental divorce and maternal-paternal histories of alcohol problems on adult offspring lifetime alcohol dependence using data from the 2001-2002 National Epidemiological Survey on Alcohol and Related Conditions (NESARC). Parental divorce and maternal-paternal alcohol problems interacted to differentially influence the likelihood of offspring lifetime alcohol dependence. Experiencing parental divorce and either maternal or paternal alcohol problems doubled the likelihood of alcohol dependence. Divorce and history of alcohol problems for both parents tripled the likelihood. Offspring of parental divorce may be more vulnerable to developing alcohol dependence, particularly when one or both parents have alcohol problems.

Host cells and methods for producing isoprenyl alkanoates

DOEpatents

Lee, Taek Soon; Fortman, Jeffrey L.; Keasling, Jay D.

2015-12-01

The invention provides for a method of producing an isoprenyl alkanoate in a genetically modified host cell. In one embodiment, the method comprises culturing a genetically modified host cell which expresses an enzyme capable of catalyzing the esterification of an isoprenol and a straight-chain fatty acid, such as an alcohol acetyltransferase (AAT), wax ester synthase/diacylglycerol acyltransferase (WS/DGAT) or lipase, under a suitable condition so that the isoprenyl alkanoate is produced.

Retinol esterification in bovine retinal pigment epithelium: reversibility of lecithin:retinol acyltransferase.

PubMed Central

Saari, J C; Bredberg, D L; Farrell, D F

1993-01-01

Esterification of all-trans-retinol is a key reaction of the vertebrate visual cycle, since it produces an insoluble, relatively non-toxic, form of the vitamin for storage and supplies substrate for the isomerization reaction. CoA-dependent and -independent pathways have been described for retinol esterification in retinal pigment epithelium (RPE). The CoA-independent reaction, catalysed by lecithin:retinol acyltransferase (LRAT) was examined in more detail in this study. Addition of retinol to RPE microsomes results in a burst of retinyl ester synthesis, followed by a rapid apparent cessation of the reaction. However, [3H]retinol, added when retinyl ester synthesis has apparently ceased, is rapidly incorporated into retinyl ester without a net increase in the amount of ester. The specific radioactivities of [3H]retinol and [3H]retinyl ester reach the same value. [14C]Palmitate from palmitoyl-CoA is incorporated into preexisting retinyl ester in the absence of net ester synthesis, too. These exchange reactions suggest that the reaction has reached equilibrium at the plateau of the progress curve and that only the accumulation of retinyl ester, and not its synthesis, has stopped during this phase of the reaction. Studies with geometrical isomers of retinol revealed that the rate of exchange of all-trans-retinol with all-trans-retinyl esters was about 6 times more rapid than exchange of 11-cis-retinol with 11-cis-retinyl ester. This is the first demonstration of the reversibility of LRAT and the first example of stereospecificity of retinyl ester synthesis in the visual system. Reversal of the LRAT reaction could contribute to the mobilization of 11-cis-retinol from 11-cis-retinyl ester pools. Images Figure 3 PMID:8489497

Lysophosphatidic Acid Acyltransferase β (LPAATβ) Promotes the Tumor Growth of Human Osteosarcoma

PubMed Central

Rastegar, Farbod; Gao, Jian-Li; Shenaq, Deana; Luo, Qing; Shi, Qiong; Kim, Stephanie H.; Jiang, Wei; Wagner, Eric R.; Huang, Enyi; Gao, Yanhong; Shen, Jikun; Yang, Ke; He, Bai-Cheng; Chen, Liang; Zuo, Guo-Wei; Luo, Jinyong; Luo, Xiaoji; Bi, Yang; Liu, Xing; Li, Mi; Hu, Ning; Wang, Linyuan; Luther, Gaurav; Luu, Hue H.; Haydon, Rex C.; He, Tong-Chuan

2010-01-01

Background Osteosarcoma is the most common primary malignancy of bone with poorly characterized molecular pathways important in its pathogenesis. Increasing evidence indicates that elevated lipid biosynthesis is a characteristic feature of cancer. We sought to investigate the role of lysophosphatidic acid acyltransferase β (LPAATβ, aka, AGPAT2) in regulating the proliferation and growth of human osteosarcoma cells. LPAATβ can generate phosphatidic acid, which plays a key role in lipid biosynthesis as well as in cell proliferation and survival. Although elevated expression of LPAATβ has been reported in several types of human tumors, the role of LPAATβ in osteosarcoma progression has yet to be elucidated. Methodology/Principal Findings Endogenous expression of LPAATβ in osteosarcoma cell lines is analyzed by using semi-quantitative PCR and immunohistochemical staining. Adenovirus-mediated overexpression of LPAATβ and silencing LPAATβ expression is employed to determine the effect of LPAATβ on osteosarcoma cell proliferation and migration in vitro and osteosarcoma tumor growth in vivo. We have found that expression of LPAATβ is readily detected in 8 of the 10 analyzed human osteosarcoma lines. Exogenous expression of LPAATβ promotes osteosarcoma cell proliferation and migration, while silencing LPAATβ expression inhibits these cellular characteristics. We further demonstrate that exogenous expression of LPAATβ effectively promotes tumor growth, while knockdown of LPAATβ expression inhibits tumor growth in an orthotopic xenograft model of human osteosarcoma. Conclusions/Significance Our results strongly suggest that LPAATβ expression may be associated with the aggressive phenotypes of human osteosarcoma and that LPAATβ may play an important role in regulating osteosarcoma cell proliferation and tumor growth. Thus, targeting LPAATβ may be exploited as a novel therapeutic strategy for the clinical management of osteosarcoma. This is especially

Developmental Regulation of Diacylglycerol Acyltransferase Family Gene Expression in Tung Tree Tissues

PubMed Central

Cao, Heping; Shockey, Jay M.; Klasson, K. Thomas; Chapital, Dorselyn C.; Mason, Catherine B.; Scheffler, Brian E.

2013-01-01

Diacylglycerol acyltransferases (DGAT) catalyze the final and rate-limiting step of triacylglycerol (TAG) biosynthesis in eukaryotic organisms. DGAT genes have been identified in numerous organisms. Multiple isoforms of DGAT are present in eukaryotes. We previously cloned DGAT1 and DGAT2 genes of tung tree (Vernicia fordii), whose novel seed TAGs are useful in a wide range of industrial applications. The objective of this study was to understand the developmental regulation of DGAT family gene expression in tung tree. To this end, we first cloned a tung tree gene encoding DGAT3, a putatively soluble form of DGAT that possesses 11 completely conserved amino acid residues shared among 27 DGAT3s from 19 plant species. Unlike DGAT1 and DGAT2 subfamilies, DGAT3 is absent from animals. We then used TaqMan and SYBR Green quantitative real-time PCR, along with northern and western blotting, to study the expression patterns of the three DGAT genes in tung tree tissues. Expression results demonstrate that 1) all three isoforms of DGAT genes are expressed in developing seeds, leaves and flowers; 2) DGAT2 is the major DGAT mRNA in tung seeds, whose expression profile is well-coordinated with the oil profile in developing tung seeds; and 3) DGAT3 is the major form of DGAT mRNA in tung leaves, flowers and immature seeds prior to active tung oil biosynthesis. These results suggest that DGAT2 is probably the major TAG biosynthetic isoform in tung seeds and that DGAT3 gene likely plays a significant role in TAG metabolism in other tissues. Therefore, DGAT2 should be a primary target for tung oil engineering in transgenic organisms. PMID:24146944

Impact of Cross-Sectoral Alcohol Policy on Youth Alcohol Consumption.

PubMed

de Goeij, Moniek C M; Jacobs, Monique A M; van Nierop, Peter; van der Veeken-Vlassak, Ivanka A G; van de Mheen, Dike; Schoenmakers, Tim M; Harting, Janneke; Kunst, Anton E

2016-07-01

Cross-sectoral alcohol policy is recommended to reduce youth alcohol consumption, but little evidence is available on its effectiveness. Therefore, we examined whether regions and municipalities in the Dutch province of Noord-Brabant with stronger cross-sectoral alcohol policy showed larger reductions in alcohol consumption among adolescents aged 12-15. Strong regional cross-sectoral alcohol policy was defined as participation in a regional alcohol prevention program. Strong municipal cross-sectoral alcohol policy was operationalized by measures on (a) sector variety: involvement of different policy sectors, and (b) strategy variety: formulation of different policy strategies. Relevant data from policy documents were searched for on the Internet. Data on trends in alcohol consumption were extracted from the 2007 and 2011 cross-sectional Youth Health Monitor that includes a random subset of adolescents aged 12-15 (n = 15,380 in 2007 and n = 15,437 in 2011). We used multilevel regression models. Two of the three regions in which municipalities participated in a regional alcohol prevention program showed a larger reduction in weekly drinking than the region in which municipalities did not participate (-12.2% and -13.4% vs. -8.3%). Municipalities with strong compared to weak sector variety showed a larger increase in adolescents' age at consuming their first alcoholic drink (0.63 vs. 0.42 years). Municipalities with strong strategy variety showed a decrease (-3.8%) in heavy weekly drinking, whereas those with weak variety showed an increase (5.1%). Cross-sectoral alcohol policy did not affect trends in other alcohol outcomes. Our results suggest that strong cross-sectoral alcohol policy may contribute to reducing some aspects of youth alcohol consumption. Monitoring policy implementation is needed to assess the full impact.

Pharmacologically induced alcohol craving in treatment seeking alcoholics correlates with alcoholism severity, but is insensitive to acamprosate

PubMed Central

Umhau, John C; Schwandt, Melanie L; Usala, Julie; Geyer, Christopher; Singley, Erick; George, David T; Heilig, Markus

2011-01-01

Modulation of alcohol craving induced by challenge stimuli may predict the efficacy of new pharmacotherapies for alcoholism. We evaluated two pharmacological challenges, the α2-adrenergic antagonist yohimbine, which reinstates alcohol seeking in rats, and the serotonergic compound meta-chlorophenylpiperazine (mCPP), previously reported to increase alcohol craving in alcoholics. To assess the predictive validity of this approach, the approved alcoholism medication acamprosate was evaluated for its ability to modulate challenge-induced cravings. A total of 35 treatment seeking alcohol dependent inpatients in early abstinence were randomized to placebo or acamprosate (2997 mg daily). Following two weeks of medication, subjects underwent three challenge sessions with yohimbine, mCPP or saline infusion under double blind conditions, carried out in counterbalanced order, and separated by at least 5 days. Ratings of cravings and anxiety, as well as biochemical measures were obtained. In all, 25 subjects completed all three sessions and were included in the analysis. Cravings were modestly, but significantly higher following both yohimbine and mCPP challenge compared with saline infusion. The mCPP, but not yohimbine significantly increased anxiety ratings. Both challenges produced robust ACTH, cortisol and prolactin responses. There was a significant correlation between craving and the degree of alcoholism severity. Acamprosate administration did not influence craving. Both yohimbine and mCPP challenges lead to elevated alcohol craving in a clinical population of alcoholics, and these cravings correlate with alcoholism severity. Under the experimental conditions used, alcohol cravings induced by these two stimuli are not sensitive to acamprosate at clinically used doses. PMID:21289601

The role of parental alcohol-specific communication in early adolescents' alcohol use.

PubMed

Van Der Vorst, Haske; Burk, William J; Engels, Rutger C M E

2010-10-01

Many alcohol prevention programs advocate conversations about alcohol between parents and children because verbal communication is the most direct way for parents to express their thoughts, rules, and concerns about alcohol to their children, so called alcohol-specific communication. Nevertheless, research on the effects of alcohol-specific communication has produced inconsistent findings. This study examined the bidirectional links between frequency of alcohol-specific communication and early adolescents' alcohol use, and the moderating effects on these links of gender and experience with alcohol. The longitudinal sample consisted of 428 Dutch early adolescents who were followed over 3 years. Results of structural equation models indicated that more frequent alcohol-specific communication at time two predicted more adolescent alcohol use at time three. Follow-up multiple-group analyses clearly show that prospective links between alcohol-specific communication and adolescent alcohol use were limited to adolescent males reporting the highest levels of drinking. For this group of drinking males, alcohol use predicted less parent-child communication, and more frequency of alcohol-specific communication predicted an increase in drinking. Alcohol-specific communication and adolescent alcohol use were not prospectively linked for males reporting lower levels of alcohol use or for adolescent females. These findings highlight the need for future research that examines both quantitative and qualitative aspects of how parents communicate with their adolescent children about alcohol. Advocation of specific parent-child communication skills meant to reduce youth alcohol use may be somewhat premature until additional studies refine our understanding of how specific parenting strategies are linked to different patterns of adolescent alcohol use. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.

Alcohol Dehydrogenase Activities of Wine Yeasts in Relation to Higher Alcohol Formation

PubMed Central

Singh, Rajendra; Kunkee, Ralph E.

1976-01-01

Alcohol dehydrogenase activities were examined in cell-free extracts of 10 representative wine yeast strains having various productivities of higher alcohols (fusel oil). The amount of fusel alcohols (n-propanol, isobutanol, active pentanol, and isopentanol) produced by the different yeasts and the specific alcohol dehydrogenase activities with the corresponding alcohols as substrates were found to be significantly related. No such relationship was found for ethanol. The amounts of higher alcohols formed during vinification could be predicted from the specific activities of the alcohol dehydrogenases with high accuracy. The results suggest a close relationship between the control of the activities of alcohol dehydrogenase and the formation of fusel oil alcohols. Also, new procedures for the prediction of higher alcohol formation during alcoholic beverage fermentation are suggested. PMID:16345179

Parental Divorce, Maternal-Paternal Alcohol Problems, and Adult Offspring Lifetime Alcohol Dependence

PubMed Central

THOMPSON, RONALD G.; ALONZO, DANA; HASIN, DEBORAH S.

2014-01-01

This study examined the influences of parental divorce and maternal-paternal histories of alcohol problems on adult offspring lifetime alcohol dependence using data from the 2001–2002 National Epidemiological Survey on Alcohol and Related Conditions (NESARC). Parental divorce and maternal-paternal alcohol problems interacted to differentially influence the likelihood of offspring lifetime alcohol dependence. Experiencing parental divorce and either maternal or paternal alcohol problems doubled the likelihood of alcohol dependence. Divorce and history of alcohol problems for both parents tripled the likelihood. Offspring of parental divorce may be more vulnerable to developing alcohol dependence, particularly when one or both parents have alcohol problems. PMID:24678271

Supported metal catalysts for alcohol/sugar alcohol steam reforming

DOE Office of Scientific and Technical Information (OSTI.GOV)

Davidson, Stephen; Zhang, He; Sun, Junming

Despite extensive studies on hydrogen production via steam reforming of alcohols and sugar alcohols, catalysts typically suffer a variety of issues from poor hydrogen selectivity to rapid deactivation. Here, we summarize recent advances in fundamental understanding of functionality and structure of catalysts for alcohol/sugar alcohol steam reforming, and provide perspectives on further development required to design highly efficient steam reforming catalysts.

Alcohol-Specific Parenting as a Mechanism of Parental Drinking and Alcohol Use Disorder Risk on Adolescent Alcohol Use Onset

PubMed Central

Handley, Elizabeth D.; Chassin, Laurie

2013-01-01

Objective: The primary aim of the current study was to examine three dimensions of alcohol-specific parenting (anti-alcohol parenting strategies, parental legitimacy in regulating adolescent drinking, and parental disclosure of negative alcohol experiences) as mechanisms in the prospective relations between parental drinking and alcohol use disorder (recovered, current, and never diagnosed) and adolescent alcohol use initiation. Method: Participants were from an ongoing longitudinal study of the intergenerational transmission of alcoholism. Structural equation modeling was used to test a maternal model (n = 268 adolescents and their mothers) and a paternal model (n = 204 adolescents and their fathers) of alcohol-specific parenting. Results: Results indicated that higher levels of drinking among mothers and current alcohol use disorder among fathers were related to more frequent parental disclosure of personal negative experiences with alcohol. Maternal disclosure of negative alcohol experiences mediated the effect of maternal drinking on adolescent onset of alcohol use such that more disclosure predicted a greater likelihood of adolescent drinking initiation at follow-up over and above general parenting. In addition, currently alcoholic mothers were perceived as having less legitimate authority to regulate adolescent drinking, and low levels of legitimacy among fathers was predictive of drinking onset among adolescents. Conclusions: Alcohol-specific parenting is a distinct and influential predictor of adolescent alcohol use initiation that is partially shaped by parents’ own drinking experiences. Moreover, parental conversations about their own personal experiences with alcohol may not represent a form of parent–child communication about drinking that deters adolescent drinking. PMID:23948527

Alcohol Outlet Characteristics and Alcohol Sales to Youth: Results of Alcohol Purchase Surveys in 45 Oregon Communities

PubMed Central

Paschall, Mallie J.; Grube, Joel W.; Black, Carol; Flewelling, Robert L.; Ringwalt, Christopher L.; Biglan, Anthony

2007-01-01

Reducing youth access to commercial sources of alcohol is recognized as a necessary component of a comprehensive strategy to reduce underage drinking and alcohol-related problems. However, research on policy-relevant factors that may influence the commercial availability of alcohol to youth is limited. The present study examines characteristics of off-premise alcohol outlets that may affect alcohol sales to youth. Random alcohol purchase surveys (N = 385) were conducted in 45 Oregon communities in 2005. Underage-looking decoys who were 21 years old but did not carry IDs were able to purchase alcohol at 34% of the outlets approached. Purchase rates were highest at convenience (38%) and grocery (36%) stores but were relatively low (14%) at other types of outlets (e.g., liquor and drug stores). Alcohol purchases were less likely at stores that were participating in the Oregon Liquor Control Commission's Responsible Vendor Program (RVP), when salesclerks asked the decoys for their IDs, and at stores with a posted underage alcohol sale warning sign. Alcohol purchases were also inversely related to the number of salesclerks present in a store, but were not related to salesclerks' age and gender. Findings of this study suggest that more frequent compliance checks by law enforcement agents should target convenience and grocery stores, and owners of off-premise outlets should require training of all salesclerks to ensure reliable checks of young-looking patron IDs, and should post underage alcohol sales warning signs in clear view of patrons. PMID:17243019

Alcohol outlet characteristics and alcohol sales to youth: results of alcohol purchase surveys in 45 Oregon communities.

PubMed

Paschall, Mallie J; Grube, Joel W; Black, Carol; Flewelling, Robert L; Ringwalt, Christopher L; Biglan, Anthony

2007-06-01

Reducing youth access to commercial sources of alcohol is recognized as a necessary component of a comprehensive strategy to reduce underage drinking and alcohol-related problems. However, research on policy-relevant factors that may influence the commercial availability of alcohol to youth is limited. The present study examines characteristics of off-premise alcohol outlets that may affect alcohol sales to youth. Random alcohol purchase surveys (N = 385) were conducted in 45 Oregon communities in 2005. Underage-looking decoys who were 21 years old but did not carry IDs were able to purchase alcohol at 34% of the outlets approached. Purchase rates were highest at convenience (38%) and grocery (36%) stores but were relatively low (14%) at other types of outlets (e.g., liquor and drug stores). Alcohol purchases were less likely at stores that were participating in the Oregon Liquor Control Commission's Responsible Vendor Program (RVP), when sales clerks asked the decoys for their IDs, and at stores with a posted underage alcohol sale warning sign. Alcohol purchases were also inversely related to the number of sales clerks present in a store, but were not related to sales clerks' age and gender. Findings of this study suggest that more frequent compliance checks by law enforcement agents should target convenience and grocery stores, and owners of off-premise outlets should require training of all sales clerks to ensure reliable checks of young-looking patron IDs, and should post underage alcohol sales warning signs in clear view of patrons.

The Conformational Flexibility of the Acyltransferase from the Disorazole Polyketide Synthase Is Revealed by an X-ray Free-Electron Laser Using a Room-Temperature Sample Delivery Method for Serial Crystallography

DOE Office of Scientific and Technical Information (OSTI.GOV)

Mathews, Irimpan I.; Allison, Kim; Robbins, Thomas

The crystal structure of the trans-acyltransferase (AT) from the disorazole polyketide synthase (PKS) was determined at room temperature to a resolution of 2.5 Å using a new method for sample delivery directly into an X-ray free-electron laser. A novel sample extractor efficiently delivered limited quantities of microcrystals directly from the native crystallization solution into the X-ray beam at room temperature. The AT structure revealed important catalytic features of this core PKS enzyme, including the occurrence of conformational changes around the active site. The implications of these conformational changes on polyketide synthase reaction dynamics are discussed.

The Conformational Flexibility of the Acyltransferase from the Disorazole Polyketide Synthase Is Revealed by an X-ray Free-Electron Laser Using a Room-Temperature Sample Delivery Method for Serial Crystallography

DOE PAGES

Mathews, Irimpan I.; Allison, Kim; Robbins, Thomas; ...

2017-08-23

The crystal structure of the trans-acyltransferase (AT) from the disorazole polyketide synthase (PKS) was determined at room temperature to a resolution of 2.5 Å using a new method for sample delivery directly into an X-ray free-electron laser. A novel sample extractor efficiently delivered limited quantities of microcrystals directly from the native crystallization solution into the X-ray beam at room temperature. The AT structure revealed important catalytic features of this core PKS enzyme, including the occurrence of conformational changes around the active site. The implications of these conformational changes on polyketide synthase reaction dynamics are discussed.

HIV/AIDS and Alcohol

MedlinePlus

... Abuse and Alcoholism (NIAAA) Main Menu Search Search form Search Alcohol & Your Health Overview of Alcohol Consumption Alcohol's Effects on the Body Alcohol Use Disorder Fetal Alcohol Exposure Support & Treatment Alcohol Policy Special Populations & Co-occurring Disorders Publications & Multimedia Brochures & ...

Tackling alcohol misuse: purchasing patterns affected by minimum pricing for alcohol.

PubMed

Ludbrook, Anne; Petrie, Dennis; McKenzie, Lynda; Farrar, Shelley

2012-01-01

Alcohol consumption is associated with a range of health and social harms that increase with the level of consumption. Policy makers are interested in effective and cost-effective interventions to reduce alcohol consumption and associated harms. Economic theory and research evidence demonstrate that increasing price is effective at the population level. Price interventions that target heavier consumers of alcohol may be more effective at reducing alcohol-related harms with less impact on moderate consumers. Minimum pricing per unit of alcohol has been proposed on this basis but concerns have been expressed that 'moderate drinkers of modest means' will be unfairly penalized. If those on low incomes are disproportionately affected by a policy that removes very cheap alcohol from the market, the policy could be regressive. The effect on households' budgets will depend on who currently purchases cheaper products and the extent to which the resulting changes in prices will impact on their demand for alcohol. This paper focuses on the first of these points. This paper aims to identify patterns of purchasing of cheap off-trade alcohol products, focusing on income and the level of all alcohol purchased. Three years (2006-08) of UK household survey data were used. The Expenditure and Food Survey provides comprehensive 2-week data on household expenditure. Regression analyses were used to investigate the relationships between the purchase of cheap off-trade alcohol, household income levels and whether the household level of alcohol purchasing is categorized as moderate, hazardous or harmful, while controlling for other household and non-household characteristics. Predicted probabilities and quantities for cheap alcohol purchasing patterns were generated for all households. The descriptive statistics and regression analyses indicate that low-income households are not the predominant purchasers of any alcohol or even of cheap alcohol. Of those who do purchase off-trade alcohol

CHRONIC ALCOHOL NEUROADAPTATION AND STRESS CONTRIBUTE TO SUSCEPTIBILITY FOR ALCOHOL CRAVING AND RELAPSE

PubMed Central

BREESE, GEORGE R.; SINHA, RAJITA; HEILIG, MARKUS

2010-01-01

Alcoholism is a chronic relapsing disorder. Major characteristics observed in alcoholics during an initial period of alcohol abstinence are altered physiological functions and a negative emotional state. Evidence suggests that a persistent, cumulative adaptation involving a kindling/allostasis-like process occurs during the course of repeated chronic alcohol exposures that is critical for the negative symptoms observed during alcohol withdrawal. Basic studies have provided evidence for specific neurotransmitters within identified brain sites being responsible for the negative emotion induced by the persistent cumulative adaptation following intermittent-alcohol exposures. After an extended period of abstinence, the cumulative alcohol adaptation increases susceptibility to stress- and alcohol cue-induced negative symptoms and alcohol seeking, both of which can facilitate excessive ingestion of alcohol. In the alcoholic, stressful imagery and alcohol cues alter physiological responses, enhance negative emotion, and induce craving. Brain fMRI imaging following stress and alcohol cues has documented neural changes in specific brain regions of alcoholics not observed in social drinkers. Such altered activity in brain of abstinent alcoholics to stress and alcohol cues is consistent with a continuing ethanol adaptation being responsible. Therapies in alcoholics found to block responses to stress and alcohol cues would presumably be potential treatments by which susceptibility for continued alcohol abuse can be reduced. By continuing to define the neurobiological basis of the sustained alcohol adaptation critical for the increased susceptibility of alcoholics to stress and alcohol cues that facilitate craving, a new era is expected to evolve in which the high rate of relapse in alcoholism is minimized. 250 PMID:20951730

Alcohol Control Policies and Alcohol Consumption by Youth: A Multi-National Study

PubMed Central

Paschall, Mallie J.; Grube, Joel W.; Kypri, Kypros

2009-01-01

Aims The study examined relationships between alcohol control policies and adolescent alcohol use in 26 countries. Design Cross-sectional analyses of alcohol policy ratings based on the Alcohol Policy Index (API), per capita consumption, and national adolescent survey data. Setting Data are from 26 countries. Participants Adolescents (15-17 years old) who participated in the 2003 ESPAD (European countries) or national secondary school surveys in Spain, Canada, Australia, New Zealand and the USA. Measurements Alcohol control policy ratings based on the API; prevalence of alcohol use, heavy drinking, and first drink by age 13 based on national secondary school surveys; per capita alcohol consumption for each country in 2003. Analysis Correlational and linear regression analyses were conducted to examine relationships between alcohol control policy ratings and past-30-day prevalence of adolescent alcohol use, heavy drinking, and having first drink by age 13. Per capita consumption of alcohol was included as a covariate in regression analyses. Findings More comprehensive API ratings and alcohol availability and advertising control ratings were inversely related to the past-30-day prevalence of alcohol use and prevalence rates for drinking 3-5 times and 6 or more times in the past 30 days. Alcohol advertising control was also inversely related to the prevalence of past-30-day heavy drinking and having first drink by age 13. Most of the relationships between API, alcohol availability and advertising control and drinking prevalence rates were attenuated and no longer statistically significant when controlling for per capita consumption in regression analyses, suggesting that alcohol use in the general population may confound or mediate observed relationships between alcohol control policies and youth alcohol consumption. Several of the inverse relationships remained statistically significant when controlling for per capita consumption. Conclusions More comprehensive and

Induction of 1-acylglycerophosphocholine acyltransferase genes by fibrates in the liver of rats.

PubMed

Yamazaki, Tohru; Wakabayashi, Michiko; Ikeda, Erika; Tanaka, Shizuyo; Sakamoto, Takeshi; Mitsumoto, Atsushi; Kudo, Naomi; Kawashima, Yoichi

2012-01-01

The effect of fibrates (clofibric acid, bezafibrate and fenofibrate) on the gene expression and activity of 1-acylglycerophosphocholine acyltransferase (LPCAT) was investigated. The administration of 0.1% (w/w) clofibric acid, bezafibrate or fenofibrate in diet for 14 d to rats induced LPCAT activity in hepatic microsomes in the following order: fenofibrate>bezafibrate>clofibric acid. The LPCAT induced by fenofibrate preferred to arachidonoyl-CoA and linoleoyl-CoA to a greater extent than did LPCAT in control microsomes. The treatment with the fibrates resulted in upregulation of the relative expression of mRNAs encoding LPCAT3 and LPCAT4 in the following order: fenofibrate>bezafibrate>clofibric acid. The administration of fibrates did not change the expression of genes encoding either LPCAT1 or LPCAT2. The treatment with fibrates elevated relative levels of both mRNAs encoding Δ6 desaturase (Fads2) and Δ5 desaturase (Fads1) in the order of fenofibrate>bezafibrate>clofibric acid, and the extent of the increase in the level of Δ6 desaturase mRNA was greater than that of Δ5 desaturase. Fatty acid profile in hepatic phosphatidylcholine (PC) was significantly changed by the treatments with fibrates. These results suggest (i) that fibrates induce LPCAT activity in hepatic microsomes by elevating the expression of genes encoding LPCAT3 and LPCAT4, (ii) that the changes in fatty acid profile of hepatic PC are, in part, due to the elevated expression of two isoforms, LPCAT3 and LPCAT4, and (iii) that the ability of fibrates to induce these changes are in the order of fenofibrate>bezafibrate>clofibric acid.

Agonistic Human Antibodies Binding to Lecithin-Cholesterol Acyltransferase Modulate High Density Lipoprotein Metabolism*

PubMed Central

Gunawardane, Ruwanthi N.; Fordstrom, Preston; Piper, Derek E.; Masterman, Stephanie; Siu, Sophia; Liu, Dongming; Brown, Mike; Lu, Mei; Tang, Jie; Zhang, Richard; Cheng, Janet; Gates, Andrew; Meininger, David; Chan, Joyce; Carlson, Tim; Walker, Nigel; Schwarz, Margrit; Delaney, John; Zhou, Mingyue

2016-01-01

Drug discovery opportunities where loss-of-function alleles of a target gene link to a disease-relevant phenotype often require an agonism approach to up-regulate or re-establish the activity of the target gene. Antibody therapy is increasingly recognized as a favored drug modality due to multiple desirable pharmacological properties. However, agonistic antibodies that enhance the activities of the target enzymes are rarely developed because the discovery of agonistic antibodies remains elusive. Here we report an innovative scheme of discovery and characterization of human antibodies capable of binding to and agonizing a circulating enzyme lecithin cholesterol acyltransferase (LCAT). Utilizing a modified human LCAT protein with enhanced enzymatic activity as an immunogen, we generated fully human monoclonal antibodies using the XenoMouseTM platform. One of the resultant agonistic antibodies, 27C3, binds to and substantially enhances the activity of LCAT from humans and cynomolgus macaques. X-ray crystallographic analysis of the 2.45 Å LCAT-27C3 complex shows that 27C3 binding does not induce notable structural changes in LCAT. A single administration of 27C3 to cynomolgus monkeys led to a rapid increase of plasma LCAT enzymatic activity and a 35% increase of the high density lipoprotein cholesterol that was observed up to 32 days after 27C3 administration. Thus, this novel scheme of immunization in conjunction with high throughput screening may represent an effective strategy for discovering agonistic antibodies against other enzyme targets. 27C3 and other agonistic human anti-human LCAT monoclonal antibodies described herein hold potential for therapeutic development for the treatment of dyslipidemia and cardiovascular disease. PMID:26644477

The alcoholism generator.

PubMed

Miller, Michael W; Spear, Linda P

2006-09-01

Alcohol exposure largely affects 3 populations: fetuses, adolescents, and adults. These 3 developmental stages are inextricably intertwined such that elevated alcohol exposure at any time increases the probability of exposure at the others. This circular interdependency is called the alcoholism generator. Furthermore, exposure to large amounts of alcohol at these 3 times can cause cognitive dysfunction, largely through mechanisms of alcohol-induced perturbations in neurogenesis and synaptogenesis. Breaking this cycle is key to reducing problem alcohol drinking and the associated sequelae.

Alcohol Expectancies Mediate and Moderate the Associations between Big Five Personality Traits and Adolescent Alcohol Consumption and Alcohol-Related Problems.

PubMed

Ibáñez, Manuel I; Camacho, Laura; Mezquita, Laura; Villa, Helena; Moya-Higueras, Jorge; Ortet, Generós

2015-01-01

Personality and expectancies are relevant psychological factors for the development of adolescent alcohol use and misuse. The present study examined their direct, mediated and moderated effects on different drinking behaviors in adolescence. Personality domains of the five-factor model, positive and negative alcohol expectancies (AEs), alcohol use during the week and the weekend, and alcohol-related problems were assessed in a sample of 361 adolescents. Different personality dimensions were directly associated with specific alcohol outcomes: Extraversion, low Conscientiousness and low Openness were associated with weekend alcohol use; low Agreeableness was related to weekday use; whereas low Agreeableness, low Conscientiousness and Extraversion were associated with alcohol-related problems. In addition, positive AEs mediated the relationship between Extraversion and alcohol use, whereas both positive and negative expectancies mediated the association between Neuroticism and alcohol consumption and alcohol-related problems. Finally, both types of expectancies interacted with Extraversion to predict alcohol problems. Our results highlight the importance of examining the complex interplay of comprehensive personality models and AEs to gain a better understanding of the development of different alcohol use and misuse patterns in adolescence.

Alcohol industry sponsorship and alcohol-related harms in Australian university sportspeople/athletes.

PubMed

O'Brien, Kerry S; Lynott, Dermot; Miller, Peter G

2013-05-01

Although there is evidence that alcohol sponsorship in sport is related to greater drinking, there is no empirical research on whether alcohol sponsorship is associated with alcohol-related harms. We examined whether there is an association between receipt of alcohol industry sponsorship, and attendance at alcohol sponsor's drinking establishments (e.g. bars), and alcohol-related aggression and antisocial behaviour in university students who play sport. University sportspeople (n = 652) completed surveys (response rate >80%) assessing receipt of alcohol industry sponsorship, attendance at sponsor's establishments and confounders [i.e. age, gender, sport type, location and alcohol consumption measured by Alcohol Use Disorders Identification Test--alcohol consumption (AUDIT-C) scores]. Participants also completed measures assessing displays and receipt of aggressive and antisocial behaviours (e.g. assaults, unwanted sexual advance, vandalism). Logistic regression models including confounders and reported attendance at alcohol sponsor's establishments showed that sportspeople receiving alcohol industry sponsorship were more likely to have been the victim of aggression (adjusted odds ratio 2.62, 95% confidence interval 1.22-5.64). Attending an alcohol sponsor's establishment was not associated with higher rates of other aggressive or antisocial behaviour. However, significant associations where found between AUDIT-C scores and having displayed and received aggression, and having damaged or had property damaged. Male sportspeople were more likely to have displayed and received aggressive and antisocial behaviour. Higher AUDIT-C scores, gender and receipt of alcohol industry sponsorship were associated with alcohol-related aggression/antisocial behaviours in university sportspeople. Sport administrators should consider action to reduce the harms associated with excessive alcohol consumption and alcohol industry sponsorship in sport. © 2012 Australasian Professional

Alcoholic liver disease.

PubMed

Penny, Steven M

2013-01-01

In the United States, approximately 100,000 deaths are attributed to alcohol abuse each year. In 2009, the World Health Organization listed alcohol use as one of the leading causes of the global burden of disease and injury. Alcoholic liver disease, a direct result of chronic alcohol abuse, insidiously destroys the normal functions of the liver. The end result of the disease, cirrhosis, culminates in a dysfunctional and diffusely scarred liver. This article discusses the clinical manifestations, imaging considerations, and treatment of alcoholic liver disease and cirrhosis. Normal liver function, liver hemodynamics, the disease of alcoholism, and the deleterious effects of alcohol also are reviewed.

Women's alcohol use and alcoholism in Korea.

PubMed

Kim, Wooksoo; Kim, Sungjae

2008-07-01

Recently South Korean society has experienced an increase in alcohol use related problems, as well as alcohol use among women. The purpose of this paper is to describe the cultural context of and to summarize the current state of knowledge of women's drinking in South Korea. Subscribing to Confucian principles, traditional Korean society has allowed drinking for men, but not for women. However, as society has changed, contemporary women drink at a younger age and consume larger amounts of alcohol than their prior generations. The current trends suggest an urgent need for research on the etiology and trajectory of women's alcohol use among various populations and the need to develop intervention programs tailored to the specific needs of women.

The reliability of alcoholism history in patients with alcohol-related cirrhosis.

PubMed

Yates, W R; Labrecque, D R; Pfab, D

1998-01-01

Alcoholic liver disease is considered an indication for liver transplantation when a candidate is felt to have a high likelihood of abstinence following transplantation. Historical variables such as duration of sobriety, duration and quantity of drinking, and treatment history are commonly used to estimate alcoholism prognosis, yet their reliability and validity in patients with alcoholic cirrhosis has received limited study. Fifty subjects (9 women and 41 men) with alcoholic cirrhosis underwent an alcoholism history interview. Each subject had a collateral source (usually a spouse) who was interviewed by a second interviewer blind to the subject's alcoholism history. The two histories were compared for duration of abstinence in months and estimated alcoholism relapse risk was calculated using the High-risk Alcoholism Relapse scale (HRAR). Duration of sobriety correlated highly between subject and collateral source (Spearman r= 0.96, P = 0.0001) as did HRAR total score (Spearman r = 0.72, P = 0.0001). Categorical assignments also showed high correlations with duration of sobriety (kappa = 0.97) and HRAR category (kappa = 0.63). When disagreements were present, collateral sources tended to underestimate severity of alcoholism. We conclude that patients with alcoholic liver disease provide a reliable history for alcoholism variables when compared with a collateral source, and that, when disagreements are present, subjects tend to report a more acute or severe alcohol problem. The results support the clinical use of patient history information in making decisions about medical interventions for alcoholic liver disease.

The Alcohol Environment Protocol: A new tool for alcohol policy.

PubMed

Casswell, Sally; Morojele, Neo; Williams, Petal Petersen; Chaiyasong, Surasak; Gordon, Ross; Gray-Philip, Gaile; Viet Cuong, Pham; MacKintosh, Anne-Marie; Halliday, Sharon; Railton, Renee; Randerson, Steve; Parry, Charles D H

2018-01-04

To report data on the implementation of alcohol policies regarding availability and marketing, and drink driving, along with ratings of enforcement from two small high-income to three high-middle income countries, and one low-middle income country. This study uses the Alcohol Environment Protocol, an International Alcohol Control study research tool, which documents the alcohol policy environment by standardised collection of data from administrative sources, observational studies and interviews with key informants to allow for cross-country comparison and change over time. All countries showed adoption to varying extents of key effective policy approaches outlined in the World Health Organization Global Strategy to Reduce the Harmful Use of Alcohol (2010). High-income countries were more likely to allocate resources to enforcement. However, where enforcement and implementation were high, policy on availability was fairly liberal. Key Informants judged alcohol to be very available in both high- and middle-income countries, reflecting liberal policy in the former and less implementation and enforcement and informal (unlicensed) sale of alcohol in the latter. Marketing was largely unrestricted in all countries and while drink-driving legislation was in place, it was less well enforced in middle-income countries. In countries with fewer resources, alcohol policies are less effective because of lack of implementation and enforcement and, in the case of marketing, lack of regulation. This has implications for the increase in consumption taking place as a result of the expanding distribution and marketing of commercial alcohol and consequent increases in alcohol-related harm. © 2018 The Authors Drug and Alcohol Review published by John Wiley & Sons Australia, Ltd on behalf of Australasian Professional Society on Alcohol and other Drugs.

Legalization of Sunday alcohol sales and alcohol consumption in the United States.

PubMed

Yörük, Barış K

2014-01-01

To investigate the relationship between legalization of Sunday alcohol sales and alcohol consumption in the United States. State-level per capita consumption of beer, wine and spirits was analyzed using difference-in-differences econometric methods. United States. Five treatment states that repealed their laws restricting Sunday alcohol sales during 1990-2007 and 12 control states that retained their Sunday alcohol laws during the same period. Outcome measures are state-level per capita consumption of overall alcohol, beer, wine and spirits. Among the states that legalized Sunday sales of alcoholic beverages, Delaware, Pennsylvania and New Mexico experienced significant increases in overall alcohol consumption (P < 0.05). However, the effect of the legalization of Sunday alcohol sales in Massachusetts and Rhode Island on per capita alcohol consumption was insignificant (P = 0.964 and P = 0.367). Three out of five states in the United States that repealed their laws restricting Sunday sale of alcoholic beverages during 1990-2007 experienced significant increases in per capita alcohol consumption. This finding implies that increased alcohol availability leads to an increase in alcohol consumption. © 2013 Society for the Study of Addiction.

Legalization of Sunday alcohol sales and alcohol consumption in the United States

PubMed Central

Yörük, Barış K.

2013-01-01

Aims To investigate the relationship between legalization of Sunday alcohol sales and alcohol consumption in the United States. Design State-level per capita consumption of beer, wine, and spirits was analyzed using difference-in-differences econometric methods. Setting United States. Participants 5 treatment states that repealed their laws restricting Sunday alcohol sales during 1990–2007 and 12 control states that retained their Sunday alcohol laws during the same period. Measurements Outcome measures are state-level per capita consumption of overall alcohol, beer, wine, and spirits. Findings Among the states that legalized Sunday sales of alcoholic beverages, Delaware, Pennsylvania, and New Mexico experienced significant increases in overall alcohol consumption (P<0.05). However, the effect of the legalization of Sunday alcohol sales in Massachusetts and Rhode Island on per capita alcohol consumption was insignificant (P=0.964 and P=0.367). Conclusions Three out of five states in the USA that repealed their laws restricting Sunday sale of alcoholic beverages during 1990–2007, experienced significant increases in per capita alcohol consumption. This finding implies that increased alcohol availability leads to an increase in alcohol consumption. PMID:24103041

College Men and Alcohol Use: Positive Alcohol Expectancies as a Mediator Between Distinct Masculine Norms and Alcohol Use

PubMed Central

Iwamoto, Derek Kenji; Corbin, William; Lejuez, Carl; MacPherson, Laura

2015-01-01

College men are more likely to engage in health-compromising behaviors including risky drinking behavior, and experience more alcohol-related problems, including violence and arrest, as compared to women. The study of masculine norms or societal expectations, defined as beliefs and values about what it means to be a man, is one promising area of investigation that may help explain within-group differences and differential rates of alcohol use among men. Using the gender social learning model, we investigated the role of positive alcohol expectancies as an underlying mediator between masculine norms and alcohol use among college men. Data from 804 college adult men (Mean age = 20.43) were collected through a web-based assessment. Participants completed a self-report measure of binge drinking, frequency of drinking, quantity of drinks, conformity to masculine norms, and positive alcohol expectancies measures. Structural equation modeling was used to examine relations between masculine norms, alcohol expectancies and alcohol use. The masculine norms of “Playboy” and Risk-Taking were positively related to heavy alcohol use, while Emotional Control and Heterosexual Presentation were both negatively associated with alcohol use, after controlling for fraternity Greek status and positive expectancies. Playboy and Winning norms were positively associated with positive expectancies while Power Over Women was inversely related to positive expectancies which, in turn, were associated with heavier alcohol use. This study was a novel exploration into the multiple pathways and mediators through which positive alcohol expectancies may help explain and provide specificity to the masculinity and alcohol use relationship among college men. PMID:25705133

College Men and Alcohol Use: Positive Alcohol Expectancies as a Mediator Between Distinct Masculine Norms and Alcohol Use.

PubMed

Iwamoto, Derek Kenji; Corbin, William; Lejuez, Carl; MacPherson, Laura

2014-01-01

College men are more likely to engage in health-compromising behaviors including risky drinking behavior, and experience more alcohol-related problems, including violence and arrest, as compared to women. The study of masculine norms or societal expectations, defined as beliefs and values about what it means to be a man, is one promising area of investigation that may help explain within-group differences and differential rates of alcohol use among men. Using the gender social learning model, we investigated the role of positive alcohol expectancies as an underlying mediator between masculine norms and alcohol use among college men. Data from 804 college adult men ( Mean age = 20.43) were collected through a web-based assessment. Participants completed a self-report measure of binge drinking, frequency of drinking, quantity of drinks, conformity to masculine norms, and positive alcohol expectancies measures. Structural equation modeling was used to examine relations between masculine norms, alcohol expectancies and alcohol use. The masculine norms of "Playboy" and Risk-Taking were positively related to heavy alcohol use, while Emotional Control and Heterosexual Presentation were both negatively associated with alcohol use, after controlling for fraternity Greek status and positive expectancies. Playboy and Winning norms were positively associated with positive expectancies while Power Over Women was inversely related to positive expectancies which, in turn, were associated with heavier alcohol use. This study was a novel exploration into the multiple pathways and mediators through which positive alcohol expectancies may help explain and provide specificity to the masculinity and alcohol use relationship among college men.

Income inequality, alcohol use, and alcohol-related problems.

PubMed

Karriker-Jaffe, Katherine J; Roberts, Sarah C M; Bond, Jason

2013-04-01

We examined the relationship between state-level income inequality and alcohol outcomes and sought to determine whether associations of inequality with alcohol consumption and problems would be more evident with between-race inequality measures than with the Gini coefficient. We also sought to determine whether inequality would be most detrimental for disadvantaged individuals. Data from 2 nationally representative samples of adults (n = 13,997) from the 2000 and 2005 National Alcohol Surveys were merged with state-level inequality and neighborhood disadvantage indicators from the 2000 US Census. We measured income inequality using the Gini coefficient and between-race poverty ratios (Black-White and Hispanic-White). Multilevel models accounted for clustering of respondents within states. Inequality measured by poverty ratios was positively associated with light and heavy drinking. Associations between poverty ratios and alcohol problems were strongest for Blacks and Hispanics compared with Whites. Household poverty did not moderate associations with income inequality. Poverty ratios were associated with alcohol use and problems, whereas overall income inequality was not. Higher levels of alcohol problems in high-inequality states may be partly due to social context.

Differently localized lysophosphatidic acid acyltransferases crucial for triacylglycerol biosynthesis in the oleaginous alga Nannochloropsis.

PubMed

Nobusawa, Takashi; Hori, Koichi; Mori, Hiroshi; Kurokawa, Ken; Ohta, Hiroyuki

2017-05-01

The production of renewable bioenergy will be necessary to meet rising global fossil fuel demands. Members of the marine microalgae genus Nannochloropsis produce large quantities of oils (triacylglycerols; TAGs), and this genus is regarded as one of the most promising for biodiesel production. Recent genome sequencing and transcriptomic studies on Nannochloropsis have provided a foundation for understanding its oleaginous trait, but the mechanism underlying oil accumulation remains to be clarified. Here we report Nannochloropsis knock-out strains of four extraplastidic lysophosphatidic acid acyltransferases (LPAT1-LPAT4) that catalyze a major de novo biosynthetic step of TAGs and membrane lipids. We found that the four LPATs are differently involved in lipid metabolic flow in Nannochloropsis. Double knock-outs among the LPATs revealed the pivotal LPATs for TAG biosynthesis, and localization analysis indicated that the stramenopile-specific LPATs (LPAT3 and LPAT4) associated with TAG synthesis reside at the perimeter of lipid droplets. No homologous region has been found with other lipid droplet-associated proteins, however. Lipid droplets are an organelle found in nearly all organisms, and recently they were shown to play important roles in cellular metabolism and signaling. Our results provide direct evidence for the importance of the perimeter of lipid droplet in TAG synthesis in addition to its known role in maintaining TAG stability, and these findings suggest that the oleaginous trait of Nannochloropsis is enabled by the acquisition of LPATs at the perimeter of lipid droplets. © 2017 The Authors. The Plant Journal published by John Wiley & Sons Ltd and Society for Experimental Biology.

Effect of apolipoprotein A-I deficiency on lecithin:cholesterol acyltransferase activation in mouse plasma.

PubMed

Parks, J S; Li, H; Gebre, A K; Smith, T L; Maeda, N

1995-02-01

Plasma cholesteryl ester (CE) synthesis by lecithin cholesterol acyltransferase (LCAT) is activated by apolipoprotein (apo)A-I. We studied the effect of plasma apoA-I concentration on LCAT activation, using normal, heterozygous or homozygous apoA-I-deficient mice made by gene targeting. Plasma esterified cholesterol concentrations of mice fed chow diets were ordered (mean +/- SEM): 105 +/- 7 (normal) > 70 +/- 5 (heterozygotes) > 26 +/- 2 (homozygotes) mg/dl. Plasma free cholesterol concentrations were similar among the three genotypes. Endogenous LCAT activity, measured as the decrease in plasma free cholesterol after a 1 h incubation at 37 degrees C, was ordered: 44 +/- 3 (normal) > 21 +/- 2 (heterozygotes) > 5 +/- 1 (homozygotes) nmol CE formed/h per ml plasma. Using a recombinant exogenous substrate consisting of egg yolk phospholipid, [14C]cholesterol, and apoA-I, CE formation of normals and heterozygotes was similar (27.4 +/- 0.6 and 28.8 +/- 1.3 nmol/h per ml plasma, respectively), but was significantly less for homozygotes (19.2 +/- 1.7 nmol/h per ml plasma). However, using a small unilamellar vesicle substrate particle containing phospholipid and [14C]cholesterol, CE formation was ordered: 1.6 +/- 0.1 (normal) = 1.6 +/- 0.1 (heterozygotes) > 0.6 +/- 0.1 (homozygotes) nmol/h per ml plasma; addition of apoA-I to the plasma of homozygous animals restored CE formation to normal levels (1.6 +/- 0.1). CE fatty acid analysis demonstrated that plasma from homozygous mice contained significantly more saturated and monounsaturated and fewer polyunsaturated fatty acids compared to normal and heterozygous mice.(ABSTRACT TRUNCATED AT 250 WORDS)

Glycerol-3-Phosphate Acyltransferase Contributes to Triacylglycerol Biosynthesis, Lipid Droplet Formation, and Host Invasion in Metarhizium robertsii

PubMed Central

Gao, Qiang; Shang, Yanfang; Huang, Wei

2013-01-01

Enzymes involved in the triacylglycerol (TAG) biosynthesis have been well studied in the model organisms of yeasts and animals. Among these, the isoforms of glycerol-3-phosphate acyltransferase (GPAT) redundantly catalyze the first and rate-limiting step in glycerolipid synthesis. Here, we report the functions of mrGAT, a GPAT ortholog, in an insect-pathogenic fungus, Metarhizium robertsii. Unlike in yeasts and animals, a single copy of the mrGAT gene is present in the fungal genome and the gene deletion mutant is viable. Compared to the wild type and the gene-rescued mutant, the ΔmrGAT mutant demonstrated reduced abilities to produce conidia and synthesize TAG, glycerol, and total lipids. More importantly, we found that mrGAT is localized to the endoplasmic reticulum and directly linked to the formation of lipid droplets (LDs) in fungal cells. Insect bioassay results showed that mrGAT is required for full fungal virulence by aiding fungal penetration of host cuticles. Data from this study not only advance our understanding of GPAT functions in fungi but also suggest that filamentous fungi such as M. robertsii can serve as a good model to elucidate the role of the glycerol phosphate pathway in fungal physiology, particularly to determine the mechanistic connection of GPAT to LD formation. PMID:24077712

Fetal Alcohol Exposure

MedlinePlus

... categories: 4 » Fetal Alcohol Syndrome (FAS) » Partial FAS (pFAS) » Alcohol-Related Neurodevelopmental Disorder (ARND) » Alcohol-Related Birth ... either prenatally, after birth, or both Partial FAS (pFAS) Partial FAS (pFAS) involves prenatal alcohol exposure, and ...

Mangiferin treatment inhibits hepatic expression of acyl-coenzyme A:diacylglycerol acyltransferase-2 in fructose-fed spontaneously hypertensive rats: a link to amelioration of fatty liver

DOE Office of Scientific and Technical Information (OSTI.GOV)

Xing, Xiaomang; Li, Danyang; Chen, Dilong

Mangiferin, a xanthone glucoside, and its associated traditional herbs have been demonstrated to improve abnormalities of lipid metabolism. However, its underlying mechanisms remain largely unclear. This study investigated the anti-steatotic effect of mangiferin in fructose-fed spontaneously hypertensive rat (SHR)s that have a mutation in sterol regulatory element binding protein (SREBP)-1. The results showed that co-administration of mangiferin (15 mg/kg, once daily, by oral gavage) over 7 weeks dramatically diminished fructose-induced increases in hepatic triglyceride content and Oil Red O-stained area in SHRs. However, blood pressure, fructose and chow intakes, white adipose tissue weight and metabolic parameters (plasma concentrations of glucose,more » insulin, triglyceride, total cholesterol and non-esterified fatty acids) were unaffected by mangiferin treatment. Mechanistically, mangiferin treatment suppressed acyl-coenzyme A:diacylglycerol acyltransferase (DGAT)-2 expression at the mRNA and protein levels in the liver. In contrast, mangiferin treatment was without effect on hepatic mRNA and/or protein expression of SREBP-1/1c, carbohydrate response element binding protein, liver pyruvate kinase, fatty acid synthase, acetyl-CoA carboxylase-1, stearoyl-CoA desaturase-1, DGAT-1, monoacyglycerol acyltransferase-2, microsomal triglyceride transfer protein, peroxisome proliferator-activated receptor-alpha, carnitine palmitoyltransferase-1 and acyl-CoA oxidase. Collectively, our results suggest that mangiferin treatment ameliorates fatty liver in fructose-fed SHRs by inhibiting hepatic DGAT-2 that catalyzes the final step in triglyceride biosynthesis. The anti-steatotic effect of mangiferin may occur independently of the hepatic signals associated with de novo fatty acid synthesis and oxidation. - Highlights: • We investigated the anti-steatotic effect of mangiferin (MA) in fructose-fed SHR. • MA (15 mg/kg/day for 7 weeks) ameliorated fructose-induced fatty

Relationship between Alcohol Purchasing Time and Alcohol Use Disorder in South Korea.

PubMed

Amista, Narcie Faith; Chun, Sungsoo; Yun, Mieun

2017-12-01

Currently, time of alcohol purchase is not part of the policies to regulate alcohol consumption in South Korea. This study was conducted to determine the relationship between alcohol purchasing time and alcohol use disorder. The survey for this study was conducted in geographically diverse regions of South Korea in 2012. Respondents' purchasing behaviors for both on-licensed (i.e., allows for consumption within the premises) and off-licensed (i.e., where alcohol is consumed off the premises) outlets and time of alcohol consumption were collected. Alcohol consumption patterns were examined using the Rapid Alcohol Problem Screen 4 (RAPS4). Data were also analyzed by age, gender and purchasing time. Results showed that among the off-licensed premises, supermarkets appear to be the most popular venue while for on-licensed premises; alcohol was generally consumed inside hotels/pubs regardless of age and gender of the purchaser. Purchasing of alcohol was highest during the day and early evening period (9:00 a.m. to 9:59 p.m.). Females are most likely to abuse alcohol than males during the early morning period and is that period after 12:00 midnight. Analysis suggests that the survey instrument used in the International Alcohol Control Study is being used to collect data on alcohol purchasing time consumption; therefore, the potential is there to provide accurate results to contribute appropriate policy responses to reduce alcohol related-harm.

Genetics of Alcoholism.

PubMed

Zhu, Ena C; Soundy, Timothy J; Hu, Yueshan

2017-05-01

Consuming excessive amounts of alcohol has the potential to modify an individual's brain and lead to alcohol dependence. Alcohol use leads to 88,000 deaths every year in the U.S. alone and can lead to other health issues including cancers, such as colorectal cancer, and mental health problems. While drinking behavior varies due to environmental factors, genetic factors also contribute to the risk of alcoholism. Certain genes affecting alcohol metabolism and neurotransmitters have been found to contribute to or inhibit the risk. Geneenvironment interactions may also play a role in the susceptibility of alcoholism. With a better understanding of the different components that can contribute to alcoholism, more personalized treatment could cater to the individual. This review discusses the major genetic factors and some small variants in other genes that contribute to alcoholism, as well as considers the gene-environmental interactions. Copyright© South Dakota State Medical Association.

Paradoxical effects of alcohol information on alcohol outcome expectancies.

PubMed

Krank, Marvin D; Ames, Susan L; Grenard, Jerry L; Schoenfeld, Tara; Stacy, Alan W

2010-07-01

Cognitive associations with alcohol predict both current and future use in youth and young adults. Much cognitive and social cognitive research suggests that exposure to information may have unconscious influences on thinking and behavior. The present study assessed the impact of information statements on the accessibility of alcohol outcome expectancies. The 2 studies reported here investigated the effects of exposure to alcohol statements typical of informational approaches to prevention on the accessibility of alcohol outcome expectancies. High school and university students were presented with information statements about the effects of alcohol and other commercial products. The alcohol statements were taken from expectancy questionnaires. Some of these statements were presented as facts and others as myths. The retention of detailed information about these statements was manipulated by (i) divided attention versus focused attention or (ii) immediate versus delayed testing. Accessibility of personal alcohol outcome expectancies was subsequently measured using an open-ended question about the expected effects of alcohol. Participants reported more alcohol outcomes seen during the information task as personal expectations about the effects of alcohol use than similar unseen items. Paradoxically, myth statements were also more likely to be reported as expectancies than unseen items in all conditions. Additionally, myth statements were generated less often than fact statements only under the condition of immediate testing with strong content processing instructions. These observations are consistent with findings from cognitive research where familiarity in the absence of explicit memory can have an unconscious influence on performance. In particular, the exposure to these items in an informational format increases accessibility of the seen items even when the participants were told that they were myths. The findings have implications for the development of

Paradoxical Effects of Alcohol Information on Alcohol Outcome Expectancies

PubMed Central

Krank, Marvin D.; Ames, Susan L.; Grenard, Jerry L.; Schoenfeld, Tara; Stacy, Alan W.

2014-01-01

Background Cognitive associations with alcohol predict both current and future use in youth and young adults. Much cognitive and social cognitive research suggests that exposure to information may have unconscious influences on thinking and behavior. The present study assessed the impact of information statements on the accessibility of alcohol outcome expectancies. Methods The 2 studies reported here investigated the effects of exposure to alcohol statements typical of informational approaches to prevention on the accessibility of alcohol outcome expectancies. High school and university students were presented with information statements about the effects of alcohol and other commercial products. The alcohol statements were taken from expectancy questionnaires. Some of these statements were presented as facts and others as myths. The retention of detailed information about these statements was manipulated by (i) divided attention versus focused attention or (ii) immediate versus delayed testing. Accessibility of personal alcohol outcome expectancies was subsequently measured using an open-ended question about the expected effects of alcohol. Results Participants reported more alcohol outcomes seen during the information task as personal expectations about the effects of alcohol use than similar unseen items. Paradoxically, myth statements were also more likely to be reported as expectancies than unseen items in all conditions. Additionally, myth statements were generated less often than fact statements only under the condition of immediate testing with strong content processing instructions. Conclusions These observations are consistent with findings from cognitive research where familiarity in the absence of explicit memory can have an unconscious influence on performance. In particular, the exposure to these items in an informational format increases accessibility of the seen items even when the participants were told that they were myths. The findings have

Exposure to alcohol advertising and alcohol consumption among Australian adolescents.

PubMed

Jones, Sandra C; Magee, Christopher A

2011-01-01

Underage drinking is a major problem in Australia and may be influenced by exposure to alcohol advertising. The objective of the present study was to collect data on 12-17 year old Australian adolescents' exposure to different types of alcohol advertising and examine the association between exposure to advertising and alcohol consumption. A cross-sectional survey of 1113 adolescents aged 12-17 years recruited with a variety of methods to gain a cross-section of participants across metropolitan, regional and rural New South Wales (including independent schools, mall intercepts and online). Participants answered a series of questions assessing adolescents' exposure to alcohol advertising across eight media (including television, Internet and point-of-sale). Alcohol consumption was assessed using three questions (initiation, recent consumption and frequency of consumption in the previous 12 months). The majority indicated that they had been exposed to alcohol advertisements on television, in newspapers and magazines, on the Internet, on billboards/posters and promotional materials and in bottleshops, bars and pubs; exposure to some of these types of alcohol advertisements was associated with increased alcohol consumption, with differences by age and gender. The results are consistent with studies from other countries and suggest that exposure to alcohol advertisements among Australian adolescents is strongly associated with drinking patterns. Given current high levels of drinking among Australian youth, these findings suggest the need to address the high levels of young people's exposure to alcohol advertising.

The relationship between exposure to alcohol advertising in stores, owning alcohol promotional items, and adolescent alcohol use.

PubMed

Hurtz, Shannon Q; Henriksen, Lisa; Wang, Yun; Feighery, Ellen C; Fortmann, Stephen P

2007-01-01

This paper describes adolescents' exposure to alcohol advertising in stores and to alcohol-branded promotional items and their association with self-reported drinking. A cross-sectional survey was administered in non-tracked required courses to sixth, seventh, and eighth graders (n = 2125) in three California middle schools. Logistic regressions compared the odds of ever (vs. never) drinking and current (vs. ever) drinking after controlling for psychosocial and other risk factors for adolescent alcohol use. Two-thirds of middle school students reported at least weekly visits to liquor, convenience, or small grocery stores where alcohol advertising is widespread. Such exposure was associated with higher odds of ever drinking, but was not associated with current drinking. One-fifth of students reported owning at least one alcohol promotional item. These students were three times more likely to have ever tried drinking and 1.5 times more likely to report current drinking than students without such items. This study provides clear evidence of an association of adolescent drinking with weekly exposure to alcohol advertising in stores and with ownership of alcohol promotional items. Given their potential influence on adolescent drinking behaviour, retail ads, and promotional items for alcohol deserve further study.

Alcoholism and Minority Populations.

ERIC Educational Resources Information Center

Watts, Thomas D.; Wright, Roosevelt, Jr.

1991-01-01

Briefly discusses some aspects of the role of the state and the position of minorities in respect to alcoholism policies and services. Includes case study of a Black alcoholic. Refers readers to studies on Black alcoholism, Native American alcoholism, Hispanic alcoholism, and Asian-American alcoholism. (Author/NB)

Personality disorders, alcohol use, and alcohol misuse.

PubMed

Maclean, Johanna Catherine; French, Michael T

2014-11-01

Personality disorders (PDs) are psychiatric conditions that manifest early in life from a mixture of genetics and environment, are highly persistent, and lead to substantial dysfunction for the affected individual and those with whom s/he interacts. In this study we offer new information on the associations between PDs and alcohol use/misuse. Specifically, we consider all 10 PDs recognized by the American Psychiatric Association; carefully address important sources of bias in our regression models; and study heterogeneity across PDs, drinking pattern, and gender. To investigate the relationships between PDs and alcohol consumption we analyze data from the 2004/2005 National Epidemiological Survey of Alcohol and Related Conditions (N=34,653). We construct measures of any drinking, drinking quantity, and patterns of misuse that could lead to significant social costs including drinking to intoxication, driving after drinking, drinking during the day, and alcohol abuse/dependence. Results show that persons with PDs are significantly more likely to use and misuse alcohol, although associations vary across gender. Moreover, antisocial, borderline, histrionic, and narcissistic PDs display the strongest links with alcohol use and misuse, and the relationships are strongest among the heaviest drinkers. These findings have important public health implications and underscore the potential social costs associated with mental health conditions. Copyright © 2014 Elsevier Ltd. All rights reserved.

Relationship between Alcohol Purchasing Time and Alcohol Use Disorder in South Korea

PubMed Central

Amista, Narcie Faith; Chun, Sungsoo; Yun, Mieun

2017-01-01

Objectives Currently, time of alcohol purchase is not part of the policies to regulate alcohol consumption in South Korea. This study was conducted to determine the relationship between alcohol purchasing time and alcohol use disorder. Methods The survey for this study was conducted in geographically diverse regions of South Korea in 2012. Respondents’ purchasing behaviors for both on-licensed (i.e., allows for consumption within the premises) and off-licensed (i.e., where alcohol is consumed off the premises) outlets and time of alcohol consumption were collected. Alcohol consumption patterns were examined using the Rapid Alcohol Problem Screen 4 (RAPS4). Data were also analyzed by age, gender and purchasing time. Results Results showed that among the off-licensed premises, supermarkets appear to be the most popular venue while for on-licensed premises; alcohol was generally consumed inside hotels/pubs regardless of age and gender of the purchaser. Purchasing of alcohol was highest during the day and early evening period (9:00 a.m. to 9:59 p.m.). Females are most likely to abuse alcohol than males during the early morning period and is that period after 12:00 midnight. Conclusion Analysis suggests that the survey instrument used in the International Alcohol Control Study is being used to collect data on alcohol purchasing time consumption; therefore, the potential is there to provide accurate results to contribute appropriate policy responses to reduce alcohol related-harm. PMID:29354399

Cross-commodity delay discounting of alcohol and money in alcohol users

PubMed Central

Moody, Lara N.; Tegge, Allison N.; Bickel, Warren K.

2017-01-01

Despite real-world implications, the pattern of delay discounting in alcohol users when the commodities now and later differ has not been well characterized. In this study, 60 participants on Amazon's Mechanical Turk completed the Alcohol Use Disorder Identification Test (AUDIT) to assess severity of use and completed four delay discounting tasks between hypothetical, equivalent amounts of alcohol and money available at five delays. The tasks included two cross-commodity (alcohol now-money later and money now-alcohol later) and two same-commodity (money now-money later and alcohol now-alcohol later) conditions. Delay discounting was significantly associated with clinical cutoffs of the AUDIT for both of the cross-commodity conditions but not for either of the same-commodity delay discounting tasks. The cross-commodity discounting conditions were related to severity of use wherein heavy users discounted future alcohol less and future money more. The change in direction of the discounting effect was dependent on the commodity that was distally available suggesting a distinctive pattern of discounting across commodities when comparing light and heavy alcohol users. PMID:29056767

Cross-commodity delay discounting of alcohol and money in alcohol users.

PubMed

Moody, Lara N; Tegge, Allison N; Bickel, Warren K

2017-06-01

Despite real-world implications, the pattern of delay discounting in alcohol users when the commodities now and later differ has not been well characterized. In this study, 60 participants on Amazon's Mechanical Turk completed the Alcohol Use Disorder Identification Test (AUDIT) to assess severity of use and completed four delay discounting tasks between hypothetical, equivalent amounts of alcohol and money available at five delays. The tasks included two cross-commodity (alcohol now-money later and money now-alcohol later) and two same-commodity (money now-money later and alcohol now-alcohol later) conditions. Delay discounting was significantly associated with clinical cutoffs of the AUDIT for both of the cross-commodity conditions but not for either of the same-commodity delay discounting tasks. The cross-commodity discounting conditions were related to severity of use wherein heavy users discounted future alcohol less and future money more. The change in direction of the discounting effect was dependent on the commodity that was distally available suggesting a distinctive pattern of discounting across commodities when comparing light and heavy alcohol users.

Are alcohol policies associated with alcohol consumption in low- and middle-income countries?

PubMed

Cook, Won Kim; Bond, Jason; Greenfield, Thomas K

2014-07-01

To examine the associations between alcohol control policies in four regulatory domains with alcohol consumption in low- and middle-income countries (LAMICs), controlling for country-level living standards and drinking patterns. Cross-sectional analyses of individual-level alcohol consumption survey data and country-level alcohol policies using multi-level modeling. Data from 15 LAMICs collected in the Gender, Alcohol, and Culture: an International Study (GENACIS) data set. Individuals aged 18-65 years. Alcohol policy data compiled by the World Health Organization; individual-level current drinking status, usual quantity and frequency of drinking, binge drinking frequency and total drinking volume; gross domestic product based on purchasing power parity (GDP-PPP) per capita; detrimental drinking pattern scale; and age and gender as individual-level covariates. Alcohol policies regulating the physical availability of alcohol, particularly those concerning business hours or involving a licensing system for off-premises alcohol retail sales, as well as minimum legal drinking age, were the most consistent predictors of alcohol consumption. Aggregate relative alcohol price levels were associated inversely with all drinking variables (P < 0.05) except drinking volume. Greater restrictions on alcohol advertising, particularly beer advertising, were associated inversely with alcohol consumption (P < 0.05). Policies that set legal blood alcohol concentration (BAC) limits for drivers and random breath testing to enforce BAC limits were not associated significantly with alcohol consumption. Alcohol policies that regulate the physical availability of alcohol are associated with lower alcohol consumption in low- and middle-income countries. © 2014 Society for the Study of Addiction.

Income Inequality, Alcohol Use, and Alcohol-Related Problems

PubMed Central

C. M. Roberts, Sarah; Bond, Jason

2013-01-01

Objectives. We examined the relationship between state-level income inequality and alcohol outcomes and sought to determine whether associations of inequality with alcohol consumption and problems would be more evident with between-race inequality measures than with the Gini coefficient. We also sought to determine whether inequality would be most detrimental for disadvantaged individuals. Methods. Data from 2 nationally representative samples of adults (n = 13 997) from the 2000 and 2005 National Alcohol Surveys were merged with state-level inequality and neighborhood disadvantage indicators from the 2000 US Census. We measured income inequality using the Gini coefficient and between-race poverty ratios (Black–White and Hispanic–White). Multilevel models accounted for clustering of respondents within states. Results. Inequality measured by poverty ratios was positively associated with light and heavy drinking. Associations between poverty ratios and alcohol problems were strongest for Blacks and Hispanics compared with Whites. Household poverty did not moderate associations with income inequality. Conclusions. Poverty ratios were associated with alcohol use and problems, whereas overall income inequality was not. Higher levels of alcohol problems in high-inequality states may be partly due to social context. PMID:23237183

75 FR 46949 - National Institute on Alcohol Abuse and Alcoholism; Notice of Meeting

Federal Register 2010, 2011, 2012, 2013, 2014

2010-08-04

... Alcohol Abuse and Alcoholism; Notice of Meeting Pursuant to section 10(d) of the Federal Advisory... intramural programs and projects conducted by the National Institute on Alcohol Abuse and Alcoholism... Branch, National Institutes of Health, National Institute on Alcohol Abuse and Alcoholism, 5635 Fishers...

Importance of alcohol-related expectations and emotional expressivity for prediction of motivation to refuse alcohol in alcohol-dependent patients.

PubMed

Slavinskienė, Justina; Žardeckaitė-Matulaitienė, Kristina

2014-01-01

The aim of this study was to evaluate the importance of alcohol-dependent patients' emotional expressivity, alcohol-related expectations and socio-demographic factors for prediction of motivation to refuse alcohol consumption. The study sample consisted of 136 alcohol-dependent patients (100 men and 36 women) undergoing treatment in Kaunas center for addictive disorders. Only higher expression of negative alcohol-related expectations (std. beta=0.192, P=0.023), higher emotional impulse intensity (std. beta=0.229, P=0.021) and higher expression of positive emotional expressiveness (std. beta=0.021, P=0.020) as well as gender (std. beta=0.180, P=0.049), education (std. beta=-0.137, P=0.038) and alcohol dependency treatment conditions (members of support group after rehabilitation program) (std. beta=0.288, P=0.001; std. beta=0.608, P=0.001) were significant factors for predicting the different level of alcohol-dependent patients motivation to refuse alcohol consumption. Negative alcohol-related expectations, emotional impulse intensity and positive emotional expressiveness were significant even though quite weak triggers for alcohol-dependent patients' different level of motivation to refuse alcohol consumption. An assumption could be made that by changing these triggers it is possible to change addictive behavior. Copyright © 2014 Lithuanian University of Health Sciences. Production and hosting by Elsevier Urban & Partner Sp. z o.o. All rights reserved.

Alcohol Policies and Alcohol-Involved Homicide Victimization in the United States.

PubMed

Naimi, Timothy S; Xuan, Ziming; Coleman, Sharon M; Lira, Marlene C; Hadland, Scott E; Cooper, Susanna E; Heeren, Timothy C; Swahn, Monica H

2017-09-01

The purpose of this study was to examine the associations between the alcohol policy environment and alcohol involvement in homicide victims in the United States, overall and by sociodemographic groups. To characterize the alcohol policy environment, the presence, efficacy, and degree of implementation of 29 alcohol policies were used to determine Alcohol Policy Scale (APS) scores by state and year. Data about homicide victims from 17 states from 2003 to 2012 were obtained from the National Violent Death Reporting System. APS scores were used as lagged exposure variables in generalized estimating equation logistic regression models to predict the individual-level odds of alcohol involvement (i.e., blood alcohol concentration [BAC] > 0.00% vs. = 0.00% and BAC ≥ 0.08% vs. ≤ 0.079%) among homicide victims. A 10 percentage point increase in APS score (representing a more restrictive policy environment) was associated with reduced odds of alcohol-involved homicide with BAC greater than 0.00% (adjusted odds ratio [AOR] = 0.89, 95% CI [0.82, 0.99]) and BAC of 0.08% or more (AOR = 0.91, 95% CI [0.82, 1.02]). In stratified analyses of homicide victims, more restrictive policy environments were significantly protective of alcohol involvement at both BAC levels among those who were female, ages 21-29 years, Hispanic, unmarried, victims of firearm homicides, and victims of homicides related to intimate partner violence. More restrictive alcohol policy environments were associated with reduced odds of alcohol-involved homicide victimization overall and among groups at high risk of homicide. Strengthening alcohol policies is a promising homicide prevention strategy.

Alcohol outlet availability and excessive alcohol consumption in breast cancer survivors.

PubMed

Schootman, Mario; Deshpande, Anjali D; Lynskey, Michael T; Pruitt, Sandi L; Lian, Min; Jeffe, Donna B

2013-01-01

Breast cancer survivors who consume alcohol excessively are at increased risk of recurrence and have worse prognosis. Because the environments in which people live shape many health behaviors, there has been increased attention to how neighborhood environments (eg, alcohol outlet availability) may influence alcohol consumption. The authors hypothesized that proximity to alcohol outlets increases the likelihood of excessive consumption (ie, more than 1 drink/day) among breast cancer survivors independent of their personal or neighborhood characteristics. With the Missouri Cancer Registry, the authors conducted a cross-sectional study of 1047 female breast cancer survivors (aged 27-96 years) 1 year after diagnosis. Using telephone interviews, the authors obtained data regarding survivors' alcohol consumption during the past 30 days and several covariates of alcohol use. They also obtained street addresses of all licensed alcohol outlets in Missouri and calculated the road network distance between a participant's address of residence and the nearest alcohol outlet, using a geographic information system. Logistic regression was used to determine if distance was independently associated with excessive alcohol consumption. Eighteen percent of participants reported consuming more than 1 drink on average per day. Women who lived within 3 miles of the nearest outlet were more likely to report excessive alcohol consumption (odds ratio: 2.09; 95% confidence interval: 1.08, 4.05) than women who lived at least 3 miles from the nearest outlet in adjusted analysis. Opportunities exist to reduce excessive alcohol use among breast cancer survivors through policy (eg, restricting number of alcohol outlets) and behavioral (eg, counseling) interventions.

Fetal alcohol syndrome

MedlinePlus

... a baby when a mother drinks alcohol during pregnancy. Causes Using alcohol during pregnancy can cause the same risks as using alcohol in general. But it poses extra risks to the unborn baby. When a pregnant woman drinks ... use during pregnancy. Larger amounts of alcohol appear to increase the ...

Corticosteroid modulation and testosterone changes during alcohol intoxication affects voluntary alcohol drinking.

PubMed

Eriksson, C J P; Etelälahti, T J; Apter, S J

2017-06-01

A number of studies have shown that stress and an activated hypothalamic-pituitary-adrenal (HPA) axis are associated with increased voluntary alcohol drinking. Recently, associations have been found between activated HPA and hypothalamic-pituitary-gonadal (HPG) axes in alcohol-preferring AA and non-preferring ANA, F2 (crossbred second generation from original AA and ANA), and Wistar rats. The aim of the present study has been to determine the role of corticosterone and alcohol-related testosterone-effects in subsequent alcohol drinking in AA, ANA, F2 and Wistar rats. The present study comprises of four substudies presenting new analyses of existing data, by which correlations between basal corticosterone levels, changes in testosterone levels during alcohol intoxications and subsequent voluntary alcohol consumption are investigated. The results displayed positive correlations between basal corticosterone levels and subsequent alcohol-mediated testosterone elevations, which was positively associated with voluntary alcohol consumption. The results also showed a negative correlation between basal corticosterone levels and alcohol-mediated testosterone decreases, which was negatively associated with alcohol consumption. In conclusion, the present study displays novel results, according to which the HPA axis, one hand, relates to testosterone elevation (potentially causing and/or strengthening reinforcement) during alcohol intoxication, which in turn may relate to higher voluntary alcohol consumption (AA rats). Vice versa, the HPA axis may also relate to alcohol-mediated testosterone decrease (causing testosterone reduction and disinforcement) and low-alcohol drinking (ANA, F2 and Wistar rats). In addition, the present results showed that alcohol-mediated testosterone changes may also, independently of the HPA axis, correlate with voluntary alcohol drinking, which indicate the impact of genetic factors. Thus, the role of the HPA-axis may be more related to situational

Searching for an environmental effect of parental alcoholism on offspring alcohol use disorder: A genetically-informed study of children of alcoholics

PubMed Central

Slutske, Wendy S.; D’Onofrio, Brian M.; Turkheimer, Eric; Emery, Robert E.; Harden, K. Paige; Heath, Andrew C.; Martin, Nicholas G.

2009-01-01

The children-of-twins design was used to isolate a potentially causal environmental impact of having an alcoholic parent on offspring alcohol use disorder by examining whether the children of alcoholics were at a higher risk for alcohol use disorders than the children of non-alcoholic parents even after correlated familial factors were controlled. Participants were 1,224 male and female twins from 836 twin pairs selected from the Australian Twin Registry, 2,334 of their 18–39 year-old offspring, and 983 spouses of the twins. Lifetime histories of DSM-IV alcohol use disorders were obtained by structured psychiatric telephone interviews conducted individually with each of the family members. Comparisons of the offspring of twins discordant for alcoholism indicated that there was no longer a statistically significant difference between the children of alcoholics and the children of non-alcoholics after genetic and family environmental factors correlated with having an alcoholic parent were controlled. The results of this study suggest that the direct causal effect of being exposed to an alcoholic parent on offspring alcohol use disorder is modest at best. PMID:18729607

Exposure to televised alcohol ads and subsequent adolescent alcohol use.

PubMed

Stacy, Alan W; Zogg, Jennifer B; Unger, Jennifer B; Dent, Clyde W

2004-01-01

To assess the impact of televised alcohol commercials on adolescents' alcohol use. Adolescents completed questionnaires about alcohol commercials and alcohol use in a prospective study. A one standard deviation increase in viewing television programs containing alcohol commercials in seventh grade was associated with an excess risk of beer use (44%), wine/liquor use (34%), and 3-drink episodes (26%) in eighth grade. The strength of associations varied across exposure measures and was most consistent for beer. Although replication is warranted, results showed that exposure was associated with an increased risk of subsequent beer consumption and possibly other consumption variables.

THE RELATIONSHIP BETWEEN EXPOSURE TO ALCOHOL ADVERTISING IN STORES, OWNING ALCOHOL PROMOTIONAL ITEMS, AND ADOLESCENT ALCOHOL USE

PubMed Central

HURTZ, SHANNON Q.; HENRIKSEN, LISA; WANG, YUN; FEIGHERY, ELLEN C.; FORTMANN, STEPHEN P.

2014-01-01

Aim This paper describes adolescents’ exposure to alcohol advertising in stores and to alcohol-branded promotional items and their association with self-reported drinking. Methods A cross-sectional survey was administered in non-tracked required courses to sixth, seventh, and eighth graders (n = 2125) in three California middle schools. Logistic regressions compared the odds of ever (vs. never) drinking and current (vs. ever) drinking after controlling for psychosocial and other risk factors for adolescent alcohol use. Results Two-thirds of middle school students reported at least weekly visits to liquor, convenience, or small grocery stores where alcohol advertising is widespread. Such exposure was associated with higher odds of ever drinking, but was not associated with current drinking. One-fifth of students reported owning at least one alcohol promotional item. These students were three times more likely to have ever tried drinking and 1.5 times more likely to report current drinking than students without such items. Conclusions This study provides clear evidence of an association of adolescent drinking with weekly exposure to alcohol advertising in stores and with ownership of alcohol promotional items. Given their potential influence on adolescent drinking behaviour, retail ads, and promotional items for alcohol deserve further study. PMID:17218364

Alcohol Abuse

ERIC Educational Resources Information Center

O'Farrell, Timothy J.; Fals-Stewart, William

2003-01-01

We received 38 controlled studies of marital and family therapy (MFT) in alcoholism treatment. We conclude that, when the alcoholic is unwilling to seek help, MFT is effective in helping the family cope better and motivating alcoholics to enter treatment. Specifically, (a) Al-Anon facilitation and referral help family members cope better; (b)…

Children of Alcoholics.

ERIC Educational Resources Information Center

Krois, Deborah Helen

Although alcoholism has long been considered a serious problem, the impact of parental alcoholism on children has only recently begun to receive attention from researchers and clinicians. A review of the empirical literature on children of alcoholics was conducted and it was concluded that children raised in an alcoholic family are at increased…

Alcohol outlet availability and excessive alcohol consumption in breast cancer survivors

PubMed Central

Schootman, Mario; Deshpande, Anjali D.; Lynskey, Michael; Pruitt, Sandi L.; Lian, Min; Jeffe, Donna B.

2014-01-01

Introduction Breast cancer survivors who consume alcohol excessively are at increased risk of recurrence and have worse prognosis. Because the environments in which people live shape many health behaviors, there has been increased attention to how neighborhood environments (e.g., alcohol outlet availability) may influence alcohol consumption. We hypothesized that proximity to alcohol outlets increases the likelihood of excessive consumption (i.e., more than one drink/day) among breast cancer survivors independent of their personal or neighborhood characteristics. Methods With the Missouri Cancer Registry, we conducted a cross-sectional study of 1047 female breast cancer survivors (aged 27–96 years) one year after diagnosis. Using telephone interviews, we obtained data regarding survivors’ alcohol consumption during the past 30 days and several covariates of alcohol use. We also obtained street addresses of all licensed alcohol outlets in Missouri and calculated the road network distance between a participant’s address of residence and the nearest alcohol outlet using a geographic information system. We used logistic regression to determine if distance was independently associated with excessive alcohol consumption or not. Results Eighteen percent of participants reported consuming more than one drink on average per day. Women who lived within 3 miles of the nearest outlet were more likely to report excessive alcohol consumption (OR: 2.09; 95% CI: 1.08 – 4.05) than women who lived at least 3 miles from the nearest outlet in adjusted analysis. Discussion Opportunities exist to reduce excessive alcohol use among breast cancer survivors through policy (e.g., restricting number of alcohol outlets) and behavioral (e.g., counseling) interventions. PMID:23799690

76 FR 17140 - National Institute on Alcohol Abuse and Alcoholism; Notice of Closed Meeting

Federal Register 2010, 2011, 2012, 2013, 2014

2011-03-28

... Alcohol Abuse and Alcoholism; Notice of Closed Meeting Pursuant to section 10(d) of the Federal Advisory... Alcohol Abuse and Alcoholism Special Emphasis Panel; RFA-AA-11-02 Alcohol Induced Metabolic and Hepatic...: Philippe Marmillot, PhD, Scientific Review Officer, National Institute on Alcohol Abuse and Alcoholism...

Alcohol-impaired motor vehicle crash risk and the location of alcohol purchase.

PubMed

Cotti, Chad; Dunn, Richard A; Tefft, Nathan

2014-05-01

Motor vehicle crashes involving alcohol impairment are among the leading causes of mortality and morbidity in the U.S. In this study, we examine how the probability of driving after a binge-drinking episode varies with the location of consumption and type of alcohol consumed. We also investigate the relationship between the location of alcohol purchase and the number of alcohol-impaired fatal motor vehicle crashes. Using multiple datasets that are representative of the U.S. between 2003 and 2009, we find that binge-drinkers are significantly more likely to drive after consuming alcohol at establishments that sell alcohol for on-premises consumption, e.g., from bars or restaurants, particularly after drinking beer. Further, per capita sales of alcohol for off-premises consumption are unrelated to the rate of alcohol-impaired fatal motor vehicle crashes. When disaggregating alcohol types, per capita sales of beer for off-premises consumption are negatively associated with the rate of alcohol-impaired fatal motor vehicle crashes. In contrast, total per capita sales of alcohol from all establishments (on- and off-premises) are positively related to the rate of alcohol-impaired fatal motor vehicle crashes and the magnitude of this relationship is strongest for beer sales. Thus, policies that shift consumption away from bars and restaurants could lead to a decline in the number of motor vehicle crashes. Copyright © 2014 Elsevier Ltd. All rights reserved.

Loss of lysophosphatidylcholine acyltransferase 1 leads to photoreceptor degeneration in rd11 mice

PubMed Central

Friedman, James S.; Chang, Bo; Krauth, Daniel S.; Lopez, Irma; Waseem, Naushin H.; Hurd, Ron E.; Feathers, Kecia L.; Branham, Kari E.; Shaw, Manessa; Thomas, George E.; Brooks, Matthew J.; Liu, Chunqiao; Bakeri, Hirva A.; Campos, Maria M.; Maubaret, Cecilia; Webster, Andrew R.; Rodriguez, Ignacio R.; Thompson, Debra A.; Bhattacharya, Shomi S.; Koenekoop, Robert K.; Heckenlively, John R.; Swaroop, Anand

2010-01-01

Retinal degenerative diseases, such as retinitis pigmentosa and Leber congenital amaurosis, are a leading cause of untreatable blindness with substantive impact on the quality of life of affected individuals and their families. Mouse mutants with retinal dystrophies have provided a valuable resource to discover human disease genes and helped uncover pathways critical for photoreceptor function. Here we show that the rd11 mouse mutant and its allelic strain, B6-JR2845, exhibit rapid photoreceptor dysfunction, followed by degeneration of both rods and cones. Using linkage analysis, we mapped the rd11 locus to mouse chromosome 13. We then identified a one-nucleotide insertion (c.420–421insG) in exon 3 of the Lpcat1 gene. Subsequent screening of this gene in the B6-JR2845 strain revealed a seven-nucleotide deletion (c.14–20delGCCGCGG) in exon 1. Both sequence changes are predicted to result in a frame-shift, leading to premature truncation of the lysophosphatidylcholine acyltransferase-1 (LPCAT1) protein. LPCAT1 (also called AYTL2) is a phospholipid biosynthesis/remodeling enzyme that facilitates the conversion of palmitoyl-lysophosphatidylcholine to dipalmitoylphosphatidylcholine (DPPC). The analysis of retinal lipids from rd11 and B6-JR2845 mice showed substantially reduced DPPC levels compared with C57BL/6J control mice, suggesting a causal link to photoreceptor dysfunction. A follow-up screening of LPCAT1 in retinitis pigmentosa and Leber congenital amaurosis patients did not reveal any obvious disease-causing mutations. Previously, LPCAT1 has been suggested to be critical for the production of lung surfactant phospholipids and biosynthesis of platelet-activating factor in noninflammatory remodeling pathway. Our studies add another dimension to an essential role for LPCAT1 in retinal photoreceptor homeostasis. PMID:20713727

Underage college students’ alcohol displays on Facebook and real-time alcohol behaviors

PubMed Central

Moreno, Megan A.; Cox, Elizabeth D.; Young, Henry N.; Haaland, Wren

2015-01-01

Purpose College is often a time of alcohol use initiation as well as displayed Facebook alcohol references. The purpose of this longitudinal study was to determine associations between initial references to alcohol on social media and college students’ self-reported recent drinking, binge drinking and excessive drinking. Methods First-year students from two US public universities were randomly selected from registrar lists for recruitment. Data collection included 2 years of monthly Facebook evaluation. When an initial displayed Facebook alcohol reference was identified, these “New Alcohol Displayers” were contacted for phone interviews. Phone interviews used the validated TimeLine FollowBack method to evaluate recent alcohol use, binge episodes and excessive drinking. Analyses included calculation of positive predictive value and Poisson regression. Results A total of 338 participants were enrolled, 56.1% were female, 74.8% were Caucasian and 58.8% were from the Midwestern university. A total of 167 (49.4%) participants became New Alcohol Displayers during the first two years of college. Among New Alcohol Displayers, 78.5% reported past 28-day alcohol use. Among New Alcohol Displayers who reported recent alcohol use, 84.9% reported at least one binge episode. Posting an initial Facebook alcohol reference as a profile picture or cover photo was positively associated with excessive drinking (RR=2.34, 95% CI: 1.54–3.58). Conclusions Findings suggest positive associations between references to alcohol on social media and self-reported recent alcohol use. Location of initial reference as a profile picture or cover photo was associated with problematic drinking, and may suggest that a student would benefit from clinical investigation or resources. PMID:26003580

Alcohol consumption and sport: a cross-sectional study of alcohol management practices associated with at-risk alcohol consumption at community football clubs

PubMed Central

2013-01-01

Background Excessive alcohol consumption is responsible for considerable harm from chronic disease and injury. Within most developed countries, members of sporting clubs participate in at-risk alcohol consumption at levels above that of communities generally. There has been limited research investigating the predictors of at-risk alcohol consumption in sporting settings, particularly at the non-elite level. The purpose of this study was to examine the association between the alcohol management practices and characteristics of community football clubs and at-risk alcohol consumption by club members. Methods A cross sectional survey of community football club management representatives and members was conducted. Logistic regression analysis (adjusting for clustering by club) was used to determine the association between the alcohol management practices (including alcohol management policy, alcohol-related sponsorship, availability of low- and non-alcoholic drinks, and alcohol-related promotions, awards and prizes) and characteristics (football code, size and location) of sporting clubs and at-risk alcohol consumption by club members. Results Members of clubs that served alcohol to intoxicated people [OR: 2.23 (95% CI: 1.26-3.93)], conducted ‘happy hour’ promotions [OR: 2.84 (95% CI: 1.84-4.38)] or provided alcohol-only awards and prizes [OR: 1.80 (95% CI: 1.16-2.80)] were at significantly greater odds of consuming alcohol at risky levels than members of clubs that did not have such alcohol management practices. At-risk alcohol consumption was also more likely among members of clubs with less than 150 players compared with larger clubs [OR:1.45 (95% CI: 1.02-2.05)] and amongst members of particular football codes. Conclusions The findings of this study suggest a need and opportunity for the implementation of alcohol harm reduction strategies targeting specific alcohol management practices at community football clubs. PMID:23947601

Alcohol and malnutrition in the pathogenesis of experimental alcoholic cardiomyopathy.

PubMed

Rossi, M A

1980-02-01

In this study, the morphology and the catecholamine levels of the myocardium in both well-nourished and malnourished alcohol-fed rats were examined. Alcohol has been administered to rats for 16 weeks. Rats fed a diet containing alcohol corresponding to 40 per cent. of total calorific intake and inadequate amounts of calories and nutrients developed morphological changes in the heart, while the controls did not. In addition, an increase in cardiac noradrenaline concentration and heart: body weight ratio could be observed. There were no differences in myocardial morphology and catecholamine concentration between well-nourished rats fed alcohol as 35 per cent. of the calorific intake and pair-fed controls. A dispute exists about whether alcohol is directly toxic to the heart or indirectly injurious due to associated dietary deficiency. The present results, taken together, make the theory of cardiotoxicity of alcohol an unlikely one, at least in the case of the rat; and they offer considerable support for the hypothesis that the association between chronic consumption of alcoholic beverages and cardiomyopathy is a result of a primary multifactorial nutritional deficiency, resulting from displacement of nutrient-associated calories by the "empty" calories--devoid of protein, vitamins, and minerals--of alcohol, and/or a secondary nutritional deficiency due to injurious effects of alcohol on the liver, pancreas and intestine. It is suggested that continued exposure to high levels of catecholamine, directly related to malnutrition, may play a role in the development of myocardial pathology.

The economics of alcohol.

PubMed

Lehto, J

1997-03-01

The use of economic arguments with regard to four aspects of alcohol policy is described and discussed. The first aspect is the impact of a potential reduction in alcohol consumption on employment by alcohol production and trade. It is shown that employment is quite independent of the level of consumption. The second aspect is the opportunity for serving the public health and state finance interests at the same time by developing alcohol taxation. The third aspect is the relationship between the public revenue from alcohol and the public costs for alcohol-related problems. A "polluter pays" principle with regard to alcohol would mean higher taxation of alcoholic beverages. The fourth aspect is the need for cost-effectiveness analyses to support the choices by the decision makers between different alcohol policy options. It is concluded that such analyses could have impact on the priorities in public health policy on alcohol.

Alcohol on campus: alcohol-related emergencies in undergraduate college students.

PubMed

Wright, S W; Norton, V C; Dake, A D; Pinkston, J R; Slovis, C M

1998-10-01

We reviewed demographic factors associated with alcohol-related disorders in undergraduates seen in the emergency department (ED) and determined the incidence of alcohol-related ED visits among undergraduates. This prospective, observational study was done in a university-affiliated emergency department. Demographic variables and incidence of students with alcohol-related disorders were analyzed. Of the 616 students seen in the ED during 1 academic year, 101 (16%) had an alcohol-related disorder. White students and freshmen were overrepresented. There were equal numbers of male and female students. The overall annual incidence for an alcohol-related visit among undergraduates was 1.7% per academic year. The incidence for freshmen was 2.9%. Four students were admitted; one died of a severe head injury. We estimate that 1 of every 15 undergraduates at our college comes to our ED with an alcohol-related problem during their 4-year college career. Younger and nonminority students were more commonly seen; there was no difference by sex. Serious outcomes included one death. This study probably underestimates the true incidence of alcohol-related disorders among students on campus.

Influence of Family Factors and Supervised Alcohol Use on Adolescent Alcohol Use and Harms: Similarities Between Youth in Different Alcohol Policy Contexts*

PubMed Central

McMorris, Barbara J.; Catalano, Richard F.; Kim, Min Jung; Toumbourou, John W.; Hemphill, Sheryl A.

2011-01-01

Objective: Harm-minimization policies suggest that alcohol use is a part of normal adolescent development and that parents should supervise their children's use to encourage responsible drinking. Zero-tolerance policies suggest that all underage alcohol use should be discouraged. This article compared hypotheses derived from harm-minimization and zero-tolerance policies regarding the influence of family context and supervised drinking on adolescent alcohol use and related harms among adolescents in Washington State, USA, and Victoria, Australia, two states that have respectively adopted zero-tolerance and harm-minimization policies. Method: Representative samples of seventh-grade students (N = 1,945; 989 females) were recruited from schools in each state. Students completed comprehensive questionnaires on alcohol use, related problem behaviors, and risk and protective factors annually from 2002 to 2004 when they were in ninth grade. Results: Relationships between family context and alcohol use and harmful use were very similar in both states. Adult-supervised settings for alcohol use were associated with higher levels of harmful alcohol consequences. Adult-supervised alcohol use mediated the links between favorable parental attitudes to alcohol use and ninth-grade alcohol use for students in both states. Conclusions: Despite policy differences in the two states, relationships between family context variables and alcohol use and harmful use are remarkably similar. Adult-supervised settings for alcohol use resulted in higher levels of harmful alcohol consequences, contrary to predictions derived from harm-minimization policy. Findings challenge the harm-minimization position that supervised alcohol use or early-age alcohol use will reduce the development of adolescent alcohol problems. PMID:21513678

Influence of family factors and supervised alcohol use on adolescent alcohol use and harms: similarities between youth in different alcohol policy contexts.

PubMed

McMorris, Barbara J; Catalano, Richard F; Kim, Min Jung; Toumbourou, John W; Hemphill, Sheryl A

2011-05-01

Harm-minimization policies suggest that alcohol use is a part of normal adolescent development and that parents should supervise their children's use to encourage responsible drinking. Zero-tolerance policies suggest that all underage alcohol use should be discouraged. This article compared hypotheses derived from harm-minimization and zero-tolerance policies regarding the influence of family context and supervised drinking on adolescent alcohol use and related harms among adolescents in Washington State, USA, and Victoria, Australia, two states that have respectively adopted zero-tolerance and harm-minimization policies. Representative samples of seventh-grade students (N = 1,945; 989 females) were recruited from schools in each state. Students completed comprehensive questionnaires on alcohol use, related problem behaviors, and risk and protective factors annually from 2002 to 2004 when they were in ninth grade. Relationships between family context and alcohol use and harmful use were very similar in both states. Adult-supervised settings for alcohol use were associated with higher levels of harmful alcohol consequences. Adult-supervised alcohol use mediated the links between favorable parental attitudes to alcohol use and ninth-grade alcohol use for students in both states. Despite policy differences in the two states, relationships between family context variables and alcohol use and harmful use are remarkably similar. Adult-supervised settings for alcohol use resulted in higher levels of harmful alcohol consequences, contrary to predictions derived from harm-minimization policy. Findings challenge the harm-minimization position that supervised alcohol use or early-age alcohol use will reduce the development of adolescent alcohol problems.

Alcohol consumption and household expenditure on alcohol in a rural district in Vietnam.

PubMed

Giang, Kim Bao; Van Minh, Hoang; Allebeck, Peter

2013-01-28

Alcohol use and alcohol-related problems are on the rise in low- and middle-income countries. Expenditure on alcohol is an important problem for families and communities and needs to be assessed. This study examines level of alcohol consumption and expenditure on alcohol in a district in Vietnam. A cross-sectional survey was conducted in a rural district in northern Vietnam. Multi-stage sampling was employed to randomly select participants from 20 communities and a town in the same district. One thousand five hundred and sixty-four adults (765 males and 799 females) aged 18-60 years were interviewed. Information about alcohol use as well as expenditure on alcohol consumption four weeks prior to the interview was gathered. Non-parametric tests and log-linear regression were employed to compare expenditure on alcohol consumption across socioeconomic groups. The prevalence of alcohol use one month prior to interview was 35% (66% among men and 5% among women). The median alcohol consumption among those who reported use of alcohol in the week prior to the interview was 7.9 standard drinks. Excessive drinking (more than 14 standard drinks per week for men and more than seven standard drinks per week for women) occurred among 35% of those who used alcohol. Median expenditure for alcohol consumption during one month by those who drank alcohol was USD 3.5, accounting for 4.6% of household food expenditure, 2.7% of total household expenditure, and 1.8% of household income. The differences in alcohol consumption and expenditure between sexes and between socioeconomic groups are also presented. Our study confirms that alcohol consumption and alcohol-related problems are common among men in Vietnam. The share of alcohol expenditure in total household expenditure is substantial, especially among poor households. This should be considered an important public health issue, which needs to be taken into account in the alcohol policy debate.

Impact of Maryland's 2011 alcohol sales tax increase on alcoholic beverage sales.

PubMed

Esser, Marissa B; Waters, Hugh; Smart, Mieka; Jernigan, David H

2016-07-01

Increasing alcohol taxes has proven effective in reducing alcohol consumption, but the effects of alcohol sales taxes on sales of specific alcoholic beverages have received little research attention. Data on sales are generally less subject to reporting biases than self-reported patterns of alcohol consumption. We aimed to assess the effects of Maryland's July 1, 2011 three percentage point increase in the alcohol sales tax (6-9%) on beverage-specific and total alcohol sales. Using county-level data on Maryland's monthly alcohol sales in gallons for 2010-2012, by beverage type, multilevel mixed effects multiple linear regression models estimated the effects of the tax increase on alcohol sales. We controlled for seasonality, county characteristics, and national unemployment rates in the main analyses. In the 18 months after the tax increase, average per capita sales of spirits were 5.1% lower (p < 0.001), beer sales were 3.2% lower (p < 0.001), and wine sales were 2.5% lower (p < 0.01) relative to what would have been expected from sales trends in the 18 months prior to the tax increase. Overall, the alcohol sales tax increase was associated with a 3.8% decline in total alcohol sold relative to what would have been expected based on sales in the prior 18 months (p < 0.001). The findings suggest that increased alcohol sales taxes may be as effective as excise taxes in reducing alcohol consumption and related problems. Sales taxes also have the added advantages of rising with inflation and taxing the highest priced beverages most heavily.

Minimum prices for alcohol and educational disparities in alcohol-related mortality.

PubMed

Herttua, Kimmo; Mäkelä, Pia; Martikainen, Pekka

2015-05-01

Minimum price of alcohol is one of the proposed set of alcohol policies in many high-income countries. However, the extent to which alcohol-related harm is associated with minimum prices across socioeconomic groups is not known. Using Finnish national registers in 1988-2007, we investigated, by means of time-series analysis, the association between minimum prices for alcohol overall, as well as for various types of alcoholic beverages, and alcohol-related mortality, among men and women ages 30-79 years across three educational groups. We defined quarterly aggregations of alcohol-related deaths, based on a sample including 80% of all deaths, in accordance with information on both underlying and contributory causes of death. About 62,500 persons died from alcohol-related causes during the 20-year follow-up. The alcohol-related mortality rate was more than threefold higher among those with a basic education than among those with a tertiary education. Among men with a basic education, an increase of 1% in the minimum price of alcohol was associated with a decrease of 0.03% (95% confidence interval = 0.01, 0.04%) in deaths per 100,000 person-years. Changes in the minimum prices of distilled spirits, intermediate products, and strong beer were also associated with changes in the opposite direction among men with a basic education and among women with a secondary education, whereas among the most highly educated there were no associations between the minimum prices of any beverages and mortality. Moreover, we found no evidence of an association between lower minimum prices for wine and higher rates of alcohol-related mortality in any of the population sub-groups. The results reveal associations between higher minimum prices and lower alcohol-related mortality among men with a basic education and women with a secondary education for all beverage types except wine.

Biochemistry of Apple Aroma: A Review.

PubMed

Espino-Díaz, Miguel; Sepúlveda, David Roberto; González-Aguilar, Gustavo; Olivas, Guadalupe I

2016-12-01

Flavour is a key quality attribute of apples defined by volatile aroma compounds. Biosynthesis of aroma compounds involves metabolic pathways in which the main precursors are fatty and amino acids, and the main products are aldehydes, alcohols and esters. Some enzymes are crucial in the production of volatile compounds, such as lipoxygenase, alcohol dehydrogenase, and alcohol acyltransferase. Composition and concentration of volatiles in apples may be altered by pre- and postharvest factors that cause a decline in apple flavour. Addition of biosynthetic precursors of volatile compounds may be a strategy to promote aroma production in apples. The present manuscript compiles information regarding the biosynthesis of volatile aroma compounds, including metabolic pathways, enzymes and substrates involved, factors that may affect their production and also includes a wide number of studies focused on the addition of biosynthetic precursors in their production.

Biochemistry of Apple Aroma: A Review

PubMed Central

Espino-Díaz, Miguel; Sepúlveda, David Roberto; González-Aguilar, Gustavo

2016-01-01

Summary Flavour is a key quality attribute of apples defined by volatile aroma compounds. Biosynthesis of aroma compounds involves metabolic pathways in which the main precursors are fatty and amino acids, and the main products are aldehydes, alcohols and esters. Some enzymes are crucial in the production of volatile compounds, such as lipoxygenase, alcohol dehydrogenase, and alcohol acyltransferase. Composition and concentration of volatiles in apples may be altered by pre- and postharvest factors that cause a decline in apple flavour. Addition of biosynthetic precursors of volatile compounds may be a strategy to promote aroma production in apples. The present manuscript compiles information regarding the biosynthesis of volatile aroma compounds, including metabolic pathways, enzymes and substrates involved, factors that may affect their production and also includes a wide number of studies focused on the addition of biosynthetic precursors in their production. PMID:28115895

Increased Behavioral Economic Demand and Craving for Alcohol following a Laboratory Alcohol Challenge

PubMed Central

Amlung, Michael; McCarty, Kayleigh N.; Morris, David H.; Tsai, Chia-Lin; McCarthy, Denis M.

2015-01-01

Background and aims Although increases in subjective alcohol craving have been observed following moderate doses of alcohol (e.g., priming effects), the effects of alcohol consumption on behavioral economic demand for alcohol are largely unstudied. This study examined the effects of alcohol intoxication on alcohol demand and craving. Design A between-subjects design in which participants were randomly assigned to either an alcohol (n = 31), placebo (n = 29) or control (n = 25) condition. Setting A laboratory setting at the University of Missouri, USA. Participants Eighty-five young adult moderate drinkers were recruited from the University of Missouri and surrounding community. Measurements Change in demand for alcohol across time was measured using three single items: alcohol consumption at no cost (i.e., intensity), maximum price paid for a single drink (i.e., breakpoint), and total amount spent on alcohol (i.e., Omax). Alcohol demand at baseline was also assessed using an alcohol purchase task (APT). Craving was assessed using a single visual analog scale item. Findings In the alcohol group compared with the combined non-alcohol groups, intensity, breakpoint, and craving increased from baseline to the ascending limb and decreased thereafter (ps < 0.05; Omax p = 0.06). Change in craving following alcohol consumption was significantly associated with change in each of the demand indices (ps < 0.0001). Finally, the demand single items were associated with corresponding indices from the APT (ps < 0.01). Conclusions Alcohol demand increases following intoxication, in terms of both the maximum amount people are willing to pay for one drink and the number of drinks people would consume if drinks were free. Behavioral economic measures of alcohol value can complement subjective craving as measures of moment-to-moment fluctuations in drinking motivation following intoxication. PMID:25732875

Underage college students' alcohol displays on Facebook and real-time alcohol behaviors.

PubMed

Moreno, Megan A; Cox, Elizabeth D; Young, Henry N; Haaland, Wren

2015-06-01

College is often a time of alcohol use initiation and displayed Facebook alcohol references. The purpose of this longitudinal study was to determine associations between initial references to alcohol on social media and college students' self-reported recent drinking, binge drinking, and excessive drinking. First-year students from two U.S. public universities were randomly selected from registrar lists for recruitment. Data collection included 2 years of monthly Facebook evaluation. When an initial displayed Facebook alcohol reference was identified, these "New Alcohol Displayers" were contacted for phone interviews. Phone interviews used the validated timeline followback method to evaluate recent alcohol use, binge episodes, and excessive drinking. Analyses included calculation of positive predictive value and Poisson regression. A total of 338 participants were enrolled; 56.1% participants were female, 74.8% were Caucasian, and 58.8% were from the Midwestern University. A total of 167 (49.4%) participants became new alcohol displayers during the first 2 years of college. Among new alcohol displayers, 78.5% reported past 28-day alcohol use. Among new alcohol displayers who reported recent alcohol use, 84.9% reported at least one binge episode. Posting an initial Facebook alcohol reference as a profile picture or cover photo was positively associated with excessive drinking (risk ratio = 2.34; 95% confidence interval, 1.54-3.58). Findings suggest positive associations between references to alcohol on social media and self-reported recent alcohol use. Location of initial reference as a profile picture or cover photo was associated with problematic drinking and may suggest that a student would benefit from clinical investigation or resources. Copyright © 2015 Society for Adolescent Health and Medicine. Published by Elsevier Inc. All rights reserved.

Recent Advances in Nicotinic Receptor Signaling in Alcohol Abuse and Alcoholism.

PubMed

Rahman, Shafiqur; Engleman, Eric A; Bell, Richard L

2016-01-01

Alcohol is the most commonly abused legal substance and alcoholism is a serious public health problem. It is a leading cause of preventable death in the world. The cellular and molecular mechanisms of alcohol reward and addiction are still not well understood. Emerging evidence indicates that unlike other drugs of abuse, such as nicotine, cocaine, or opioids, alcohol targets numerous channel proteins, receptor molecules, and signaling pathways in the brain. Previously, research has identified brain nicotinic acetylcholine receptors (nAChRs), a heterogeneous family of pentameric ligand-gated cation channels expressed in the mammalian brain, as critical molecular targets for alcohol abuse and dependence. Genetic variations encoding nAChR subunits have been shown to increase the vulnerability to develop alcohol dependence. Here, we review recent insights into the rewarding effects of alcohol, as they pertain to different nAChR subtypes, associated signaling molecules, and pathways that contribute to the molecular mechanisms of alcoholism and/or comorbid brain disorders. Understanding these cellular changes and molecular underpinnings may be useful for the advancement of brain nicotinic-cholinergic mechanisms, and will lead to a better translational and therapeutic outcome for alcoholism and/or comorbid conditions. Copyright © 2016. Published by Elsevier Inc.

The effect of alcohol price on dependent drinkers' alcohol consumption.

PubMed

Falkner, Carolyn; Christie, Grant; Zhou, Lifeng; King, Julian

2015-12-18

To investigate the current purchasing behaviours of a group of dependent drinkers and their potential response to future increases in the price of alcohol. 115 clients undergoing medical detoxification completed an anonymous survey about their daily alcohol consumption, its cost, their response to potential price increases and strategies previously used when unable to afford alcohol. Mean and median number of standard drinks consumed per day was 24, at a median cost of $25 NZD (95%CI $22, $30). Thirty-six per cent (95%CI 26%, 46%) of the group bought alcohol at $1 or less per standard drink, and the median number of drinks consumed per day (30) by this group was significantly higher (p=0.0028) than the rest of the sample (22.5). The most common strategy used if no money was available to purchase alcohol was to forgo essentials. If facing a potential price rise, 77% (95%CI 69%, 85%) would switch wholly or partially to a cheaper product and 13% (95%CI 8%, 21%) would cut down their drinking. Although the majority of our group would be financially impacted by an increase in the minimum price per standard drink, any potential impacts would be most significant in those buying the cheapest alcohol (who also drink the most), suggesting that minimum pricing may be an important harm minimisation strategy in this group. A minimum price per standard drink would limit the possibility of switching to an alternate cheaper product and likely result in an overall reduction in alcohol consumption in this group. Stealing alcohol, or the use of non-beverage alcohol, were seldom reported as previous strategies used in response to unaffordable alcohol and fears of such are not valid reasons for rejecting minimum pricing to reduce general population consumption.

Effect of fetal alcohol exposure on adult symptoms of nicotine, alcohol, and drug dependence.

PubMed

Yates, W R; Cadoret, R J; Troughton, E P; Stewart, M; Giunta, T S

1998-06-01

The objective of this study is to examine the effect of fetal alcohol exposure on later substance dependence using an adoption study method. One hundred ninety-seven adoptees were interviewed for substance abuse disorders, including nicotine, alcohol, and drug dependence. Twenty-one adoptees had mothers who drank during pregnancy. Adoptees with fetal alcohol exposure were compared with those without fetal alcohol exposure for symptoms of adult nicotine, alcohol, and drug dependence. Adoptee symptom counts for alcohol, drug, and nicotine dependence were higher for those exposed to alcohol in utero. The effect of fetal alcohol exposure remained after controlling for gender, biological parent alcohol dependence diagnosis, birth weight, gestational age and other environmental variables. Fetal alcohol exposure may produce increased risk for later nicotine, alcohol, and drug dependence. Possible effects of fetal alcohol exposure on development of adult substance use patterns needs attention in genetic studies of substance abuse.

Health risks of alcohol use

MedlinePlus

Alcoholism - risks; Alcohol abuse - risks; Alcohol dependence - risks; Risky drinking ... pubmed/23698791 . National Institute on Alcohol Abuse and Alcoholism website. Alcohol use disorder. www.niaaa.nih.gov/ ...

Combined alcohol and energy drink use: hedonistic motives, adenosine, and alcohol dependence.

PubMed

Marczinski, Cecile A

2014-07-01

Consumption of alcohol mixed with energy drinks (AmED) has been associated with both short- and long-term risks beyond those observed with alcohol alone. AmED use has been associated with heavy episodic (binge) drinking, risky behaviors, and risk of alcohol dependence. Laboratory research has demonstrated that AmED beverages lead to greater motivation to drink versus the same amount of alcohol consumed alone. However, the reason consumers find AmED beverages particularly appealing has been unclear. A recent report by Droste and colleagues (Alcohol Clin Exp Res 2014; 38:2087-2095) is the first study to investigate motivations related to AmED consumption and to determine which motives predict AmED consumption patterns, experience of drinking-related harms, and risk of alcohol dependence. The findings of this study significantly enhance our understanding of why AmED consumption is related to the risk of alcohol dependence and change our understanding of why consumers choose AmED beverages. The authors report that hedonistic motives strongly predicted AmED use and the harms associated with use. While intoxication-reduction motives predicted self-reported accidents and injuries, these motives did not predict AmED consumption patterns and risk of dependence. The risk of alcohol dependence may arise from repeated experiences when drinking alcohol is more pleasurable when energy drinks are consumed with the alcohol. This commentary will focus on why energy drinks might increase the rewarding properties of alcohol in social drinkers. In addition, discussion is provided explaining why more research on the neurotransmitter, adenosine, may actually inform us about the mechanisms contributing to the development of alcohol dependence. Copyright © 2014 by the Research Society on Alcoholism.

The Mitochondrial Cardiolipin Remodeling Enzyme Lysocardiolipin Acyltransferase Is a Novel Target in Pulmonary Fibrosis

PubMed Central

Huang, Long Shuang; Mathew, Biji; Zhao, Yutong; Noth, Imre; Reddy, Sekhar P.; Harijith, Anantha; Usatyuk, Peter V.; Berdyshev, Evgeny V.; Kaminski, Naftali; Zhou, Tong; Zhang, Wei; Zhang, Yanmin; Rehman, Jalees; Kotha, Sainath R.; Gurney, Travis O.; Parinandi, Narasimham L.; Lussier, Yves A.; Garcia, Joe G. N.

2014-01-01

Rationale: Lysocardiolipin acyltransferase (LYCAT), a cardiolipin-remodeling enzyme regulating the 18:2 linoleic acid pattern of mammalian mitochondrial cardiolipin, is necessary for maintaining normal mitochondrial function and vascular development. We hypothesized that modulation of LYCAT expression in lung epithelium regulates development of pulmonary fibrosis. Objectives: To define a role for LYCAT in human and murine models of pulmonary fibrosis. Methods: We analyzed the correlation of LYCAT expression in peripheral blood mononuclear cells (PBMCs) with the outcomes of pulmonary functions and overall survival, and used the murine models to establish the role of LYCAT in fibrogenesis. We studied the LYCAT action on cardiolipin remodeling, mitochondrial reactive oxygen species generation, and apoptosis of alveolar epithelial cells under bleomycin challenge. Measurements and Main Results: LYCAT expression was significantly altered in PBMCs and lung tissues from patients with idiopathic pulmonary fibrosis (IPF), which was confirmed in two preclinical murine models of IPF, bleomycin- and radiation-induced pulmonary fibrosis. LYCAT mRNA expression in PBMCs directly and significantly correlated with carbon monoxide diffusion capacity, pulmonary function outcomes, and overall survival. In both bleomycin- and radiation-induced pulmonary fibrosis murine models, hLYCAT overexpression reduced several indices of lung fibrosis, whereas down-regulation of native LYCAT expression by siRNA accentuated fibrogenesis. In vitro studies demonstrated that LYCAT modulated bleomycin-induced cardiolipin remodeling, mitochondrial membrane potential, reactive oxygen species generation, and apoptosis of alveolar epithelial cells, potential mechanisms of LYCAT-mediated lung protection. Conclusions: This study is the first to identify modulation of LYCAT expression in fibrotic lungs and offers a novel therapeutic approach for ameliorating lung inflammation and pulmonary fibrosis. PMID

78 FR 66015 - National Institute on Alcohol Abuse and Alcoholism; Notice of Closed Meeting

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2013-11-04

... Alcohol Abuse and Alcoholism; Notice of Closed Meeting Pursuant to section 10(d) of the Federal Advisory... Alcohol Abuse and Alcoholism Special Emphasis Panel; AA-2 Deferred Grant Application Review. Date...: National Institute on Alcohol Abuse and Alcoholism, 5635 Fishers Lane (Teleconference), Rockville, MD 20852...

76 FR 2129 - National Institute on Alcohol Abuse and Alcoholism; Notice of Closed Meeting

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2011-01-12

... Alcohol Abuse and Alcoholism; Notice of Closed Meeting Pursuant to section 10(d) of the Federal Advisory... and Alcoholism, Special Emphasis Panel, ``Review of the Prenatal Alcohol in Sudden Infant Death... Officer, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, 5635 Fishers...

75 FR 10808 - National Institute on Alcohol Abuse and Alcoholism; Notice of Closed Meeting

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2010-03-09

... Alcohol Abuse and Alcoholism; Notice of Closed Meeting Pursuant to section 10(d) of the Federal Advisory... and Alcoholism Special Emphasis Panel; Review of Alcohol Resource Grant Applications. Date: April 6...: Richard A Rippe, Ph.D., Scientific Review Officer, National Institute on Alcohol Abuse & Alcoholism...

75 FR 42451 - National Institute on Alcohol Abuse and Alcoholism; Notice of Closed Meeting

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2010-07-21

... Alcohol Abuse and Alcoholism; Notice of Closed Meeting Pursuant to section 10(d) of the Federal Advisory... and Alcoholism, Special Emphasis Panel, Review of Alcohol Research Centers' Applications. Date: August...: Richard Rippe, PhD, Scientific Review Officer, National Institute on Alcohol Abuse and Alcoholism...

Functional group and stereochemical requirements for substrate binding by ghrelin O-acyltransferase revealed by unnatural amino acid incorporation.

PubMed

Cleverdon, Elizabeth R; Davis, Tasha R; Hougland, James L

2018-04-21

Ghrelin is a small peptide hormone that undergoes a unique posttranslational modification, serine octanoylation, to play its physiological roles in processes including hunger signaling and glucose metabolism. Ghrelin O-acyltransferase (GOAT) catalyzes this posttranslational modification, which is essential for ghrelin to bind and activate its cognate GHS-R1a receptor. Inhibition of GOAT offers a potential avenue for modulating ghrelin signaling for therapeutic effect. Defining the molecular characteristics of ghrelin that lead to binding and recognition by GOAT will facilitate the development and optimization of GOAT inhibitors. We show that small peptide mimics of ghrelin substituted with 2,3-diaminopropanoic acid in place of the serine at the site of octanoylation act as submicromolar inhibitors of GOAT. Using these chemically modified analogs of desacyl ghrelin, we define key functional groups within the N-terminal sequence of ghrelin essential for binding to GOAT and determine GOAT's tolerance to backbone methylations and altered amino acid stereochemistry within ghrelin. Our study provides a structure-activity analysis of ghrelin binding to GOAT that expands upon activity-based investigations of ghrelin recognition and establishes a new class of potent substrate-mimetic GOAT inhibitors for further investigation and therapeutic interventions targeting ghrelin signaling. Copyright © 2018 Elsevier Inc. All rights reserved.

Novel acyl-CoA: cholesterol acyltransferase inhibitor: indoline-based sulfamide derivatives with low lipophilicity and protein binding ratio.

PubMed

Takahashi, Kenji; Ohta, Masaru; Shoji, Yoshimichi; Kasai, Masayasu; Kunishiro, Kazuyoshi; Miike, Tomohiro; Kanda, Mamoru; Shirahase, Hiroaki

2010-08-01

To find a novel acyl-CoA: cholesterol acyltransferase inhibitor, a series of sulfamide derivatives were synthesized and evaluated. Compound 1d, in which carboxymethyl moiety at the 5-position of Pactimibe was replaced by a sulfamoylamino group, showed 150-fold more potent anti-foam cell formation activity (IC(50): 0.02 microM), 1.6-fold higher log D(7.0) (4.63), and a slightly lower protein binding ratio (93.2%) than Pactimibe. Compound 1i, in which the octyl chain at the 1-position in 1d was replaced by an ethoxyethyl, showed markedly low log D(7.0) (1.73) and maintained 3-fold higher anti-foam cell formation activity (IC(50): 1.0 microM), than Pactimibe. The plasma protein binding ratio (PBR) of 1i was much lower than that of Pactimibe (62.5% vs. 98.1%), and its partition ratio to the rabbit atherosclerotic aorta after oral administration was higher than that of Pactimibe. Compound 1i at 10 microM markedly inhibited cholesterol esterification in atherosclerotic rabbit aortas even when incubated with serum, while Pactimibe had little effect probably due to its high PBR. In conclusion, compound 1i is expected to more efficiently inhibit the progression of atherosclerosis than Pactimibe.

Alcohol and the Intestine

PubMed Central

Patel, Sheena; Behara, Rama; Swanson, Garth R.; Forsyth, Christopher B.; Voigt, Robin M.; Keshavarzian, Ali

2015-01-01

Alcohol abuse is a significant contributor to the global burden of disease and can lead to tissue damage and organ dysfunction in a subset of alcoholics. However, a subset of alcoholics without any of these predisposing factors can develop alcohol-mediated organ injury. The gastrointestinal tract (GI) could be an important source of inflammation in alcohol-mediated organ damage. The purpose of review was to evaluate mechanisms of alcohol-induced endotoxemia (including dysbiosis and gut leakiness), and highlight the predisposing factors for alcohol-induced dysbiosis and gut leakiness to endotoxins. Barriers, including immunologic, physical, and biochemical can regulate the passage of toxins into the portal and systemic circulation. In addition, a host of environmental interactions including those influenced by circadian rhythms can impact alcohol-induced organ pathology. There appears to be a role for therapeutic measures to mitigate alcohol-induced organ damage by normalizing intestinal dysbiosis and/or improving intestinal barrier integrity. Ultimately, the inflammatory process that drives progression into organ damage from alcohol appears to be multifactorial. Understanding the role of the intestine in the pathogenesis of alcoholic liver disease can pose further avenues for pathogenic and treatment approaches. PMID:26501334

Alcoholic liver disease and pancreatitis: global health problems being addressed by the US National Institute on Alcohol Abuse and Alcoholism.

PubMed

Warren, Kenneth R; Murray, Margaret M

2013-08-01

The review article summarizes the mission of the National Institute on Alcohol Abuse and Alcoholism (NIAAA) with focus on the NIAAA's current and future research version for alcoholic liver disease and alcoholic pancreatitis. © 2013 Journal of Gastroenterology and Hepatology Foundation and Wiley Publishing Asia Pty Ltd.

77 FR 54919 - National Institute on Alcohol Abuse and Alcoholism; Notice of Closed Meeting

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2012-09-06

... Alcohol Abuse and Alcoholism; Notice of Closed Meeting Pursuant to section 10(d) of the Federal Advisory... Alcohol Abuse and Alcoholism Initial Review Group Biomedical Research Review Subcommittee. Date: October... Alcohol Abuse and Alcoholism, 5635 Fishers Lane, Rm 2019, Bethesda, MD 20892, 301-443-2861, marmillotp...

78 FR 38353 - National Institute on Alcohol Abuse and Alcoholism; Notice of Closed Meeting

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2013-06-26

... Alcohol Abuse and Alcoholism; Notice of Closed Meeting Pursuant to section 10(d) of the Federal Advisory... Alcohol Abuse and Alcoholism Special Emphasis Panel; Review of Applications on HIV- AIDS/Alcohol....273, Alcohol Research Programs; National Institutes of Health, HHS) Dated: June 19, 2013. Carolyn A...

75 FR 71711 - National Institute on Alcohol Abuse and Alcoholism; Notice of Closed Meeting

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2010-11-24

... Alcohol Abuse and Alcoholism; Notice of Closed Meeting Pursuant to section 10(d) of the Federal Advisory... Alcohol Abuse and Alcoholism Initial Review Group; Neuroscience Review Subcommittee. Date: March 8-9, 2011..., Scientific Review Officer, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health...

Fetal Alcohol Spectrum Disorders.

PubMed

Williams, Janet F; Smith, Vincent C

2015-11-01

Prenatal exposure to alcohol can damage the developing fetus and is the leading preventable cause of birth defects and intellectual and neurodevelopmental disabilities. In 1973, fetal alcohol syndrome was first described as a specific cluster of birth defects resulting from alcohol exposure in utero. Subsequently, research unequivocally revealed that prenatal alcohol exposure causes a broad range of adverse developmental effects. Fetal alcohol spectrum disorder (FASD) is the general term that encompasses the range of adverse effects associated with prenatal alcohol exposure. The diagnostic criteria for fetal alcohol syndrome are specific, and comprehensive efforts are ongoing to establish definitive criteria for diagnosing the other FASDs. A large and growing body of research has led to evidence-based FASD education of professionals and the public, broader prevention initiatives, and recommended treatment approaches based on the following premises:▪ Alcohol-related birth defects and developmental disabilities are completely preventable when pregnant women abstain from alcohol use.▪ Neurocognitive and behavioral problems resulting from prenatal alcohol exposure are lifelong.▪ Early recognition, diagnosis, and therapy for any condition along the FASD continuum can result in improved outcomes.▪ During pregnancy:◦no amount of alcohol intake should be considered safe;◦there is no safe trimester to drink alcohol;◦all forms of alcohol, such as beer, wine, and liquor, pose similar risk; and◦binge drinking poses dose-related risk to the developing fetus. Copyright © 2015 by the American Academy of Pediatrics.

Effect of alcohol references in music on alcohol consumption in public drinking places.

PubMed

Engels, Rutger C M E; Slettenhaar, Gert; ter Bogt, Tom; Scholte, Ron H J

2011-01-01

People are exposed to many references to alcohol, which might influence their consumption of alcohol directly. In a field experiment, we tested whether textual references to alcohol in music played in bars lead to higher revenues of alcoholic beverages. We created two databases: one contained songs referring to alcohol, the parallel database contained songs with matching artists, tempo, and energetic content, but no references to alcohol. Customers of three bars were exposed to either music textually referring to alcohol or to the control condition, resulting in 23 evenings in both conditions. Bartenders were instructed to play songs with references to alcohol (or not) during a period of 2 hours each of the evenings of interest. They were not blind to the experimental condition. The results showed that customers who were exposed to music with textual references to alcohol spent significantly more on alcoholic drinks compared to customers in the control condition. This pilot study provides preliminary evidence that alcohol-related lyrics directly affect alcohol consumption in public drinking places. Since our study is one of the first testing direct effects of music lyrics on consumption, our small-scale, preliminary study needs replication before firm conclusions can be drawn. Copyright © American Academy of Addiction Psychiatry.

77 FR 64117 - National Institute on Alcohol Abuse and Alcoholism; Notice of Closed Meeting

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2012-10-18

... Alcohol Abuse and Alcoholism; Notice of Closed Meeting Pursuant to section 10(d) of the Federal Advisory... Alcohol Abuse and Alcoholism Special Emphasis Panel. Name of Committee: Date: November 5, 2012. Time: 2:30.... Rippe, Ph.D., Scientific Review Officer, National Institute on Alcohol Abuse and Alcoholism, 5635...

Information on Blood Alcohol Concentration: Evaluation of Two Alcohol Nomograms.

ERIC Educational Resources Information Center

Werch, Chudley E.

1988-01-01

Compared utility of two common alcohol nomograms on impacting decisions regarding drinking, driving after drinking, knowledge of relationship between personal alcohol consumption and the legal level of intoxication, and consumer evaluation measures, to utility of alcohol information warning card. Nomograms were no more effective than cards warning…

Fetal Alcohol Syndrome and Fetal Alcohol Effects in Child Development.

ERIC Educational Resources Information Center

Pancratz, Diane R.

This literature review defines Fetal Alcohol Syndrome (FAS) and Fetal Alcohol Effects (FAE) and considers their causes, diagnoses, prevalence, and educational ramifications. Effects of alcohol during each of the trimesters of pregnancy are summarized. Specific diagnostic characteristics of FAS are listed: (1) growth deficiency, (2) a…

78 FR 17680 - National Institute on Alcohol Abuse and Alcoholism; Closed Meeting

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2013-03-22

... Alcohol Abuse and Alcoholism; Closed Meeting Pursuant to section 10(d) of the Federal Advisory Committee... unwarranted invasion of personal privacy. Name of Committee: National Institute on Alcohol Abuse and.... 93.273, Alcohol Research Programs; National Institutes of Health, HHS) Dated: March 18, 2013. Carolyn...

Comparison of Alcohol Consumption and Alcohol Policies in the Czech Republic and Norway.

PubMed

Hnilicová, Helena; Nome, Siri; Dobiášová, Karolína; Zvolský, Miroslav; Henriksen, Roger; Tulupova, Elena; Kmecová, Zuzana

2017-06-01

The Czech Republic is characterized by high alcohol consumption and is well known as the world's biggest consumer of beer. In contrast, the alcohol consumption in Norway is relatively low. In this article, we describe and discuss alcohol policy development in the Czech Republic since the mid-1980s to the present and its impact on the alcohol consumption and compare our findings, including the dynamics of the total alcohol consumption and the development of drinking patterns among young people, with the situation in Norway. The study uses the methodology of "process tracing". Selected national statistics, research outcomes and related policy documents were analyzed to identify possible relations between the alcohol consumption and the alcohol policy in two different environments and institutional/policy settings. There was a clear difference in alcohol consumption trends in both countries in the last three decades. Norway was characterized by low alcohol consumption with tendency to decline in the last years. In contrast, the Czech Republic showed an upward trend. In addition, alcohol consumption among Czech youth has been continuously increasing since 1995, whereas the opposite trend has occurred in Norway since the late 1990s. The results revealed that the alcohol-control policies of the Czech Republic and Norway were significantly different during the study period. Norway had a very restrictive alcohol policy, in contrast to the liberal alcohol policy adopted in the Czech Republic, in particular after political transition in 1990. Liberalization of social life together with considerable decline of alcohol price due to complete privatization of alcohol production and sale contributed to an increase of the alcohol consumption in the Czech Republic. Persistently high alcohol consumption among general population and its growth among young people in the Czech Republic pose social, economic and health threats. Norway could provide the inspiration to Czech politicians

Lysophosphatidylcholine acyltransferase1 overexpression promotes oral squamous cell carcinoma progression via enhanced biosynthesis of platelet-activating factor.

PubMed

Shida-Sakazume, Tomomi; Endo-Sakamoto, Yosuke; Unozawa, Motoharu; Fukumoto, Chonji; Shimada, Ken; Kasamatsu, Atsushi; Ogawara, Katsunori; Yokoe, Hidetaka; Shiiba, Masashi; Tanzawa, Hideki; Uzawa, Katsuhiro

2015-01-01

The relevance of lysophosphatidylcholine acyltransferase1 (LPCAT1), a cytosolic enzyme in the remodeling pathway of phosphatidylcholine metabolism, in oral squamous cell carcinoma (OSCC) is unknown. We investigated LPCAT1 expression and its functional mechanism in OSCCs. We analyzed LPCAT1 mRNA and protein expression levels in OSCC-derived cell lines. Immunohistochemistry was performed to identify correlations between LPCAT1 expression levels and primary OSCCs clinicopathological status. We established LPCAT1 knockdown models of the OSCC-derived cell lines (SAS, Ca9-22) for functional analysis and examined the association between LPCAT1 expression and the platelet-activating factor (PAF) concentration and PAF-receptor (PAFR) expression. LPCAT1 mRNA and protein were up-regulated significantly (p<0.05) in OSCC-derived cell lines compared with human normal oral keratinocytes. Immunohistochemistry showed significantly (p<0.05) elevated LPCAT1 expression in primary OSCCs compared with normal counterparts and a strong correlation between LPCAT1-positive OSCCs and tumoral size and regional lymph node metastasis. In LPCAT1 knockdown cells, cellular proliferation and invasiveness decreased significantly (p<0.05); cellular migration was inhibited compared with control cells. Down-regulation of LPCAT1 resulted in a decreased intercellular PAF concentration and PAFR expression. LPCAT1 was overexpressed in OSCCs and correlated with cellular invasiveness and migration. LPCAT1 may contribute to tumoral growth and metastasis in oral cancer.

The density of alcohol outlets and adolescent alcohol consumption: An Australian longitudinal analysis.

PubMed

Rowland, B; Evans-Whipp, Tracy; Hemphill, Sheryl; Leung, Rachel; Livingston, M; Toumbourou, J W

2016-01-01

Higher density of alcohol outlets has been linked to increased levels of adolescent alcohol-related behaviour. Research to date has been cross-sectional. A longitudinal design using two waves of annual survey data from the Australian arm of the International Youth Development Study was used. The sample comprised 2835 individuals with average age at wave 2 of 14 years (SD=1.67; range=11-17 years). GSEM was used to examine how absolute levels of alcohol outlet density was associated with student-reported alcohol use one year later, while controlling for prior alcohol use, risk factors at wave one and changes in density over the 2 years. Adolescents' perception of alcohol availability and friends' alcohol use were tested as potential mediators of the association between alcohol outlet density and adolescent alcohol use. Elasticity modelling identified a 10% increase in overall density at wave one was associated with an approximately 17% increase in odds of adolescent alcohol consumption at wave two. Living in areas with a higher density of outlets was associated with a statistically significant increase in the likelihood of adolescents developing early age alcohol consumption. Copyright © 2015 Elsevier Ltd. All rights reserved.

Impulsivity and Alcohol Demand in relation to Combined Alcohol and Caffeine Use

PubMed Central

Amlung, Michael; Few, Lauren R.; Howland, Jonathan; Rohsenow, Damaris J.; Metrik, Jane; MacKillop, James

2014-01-01

Problematic alcohol use among college students continues to be a prominent concern in the United States, including the growing trend of consuming caffeine with alcoholic beverages (CABs). Epidemiologically, CAB use is associated with incremental risks from drinking, although these relationships could be due to common predisposing factors rather than specifically due to CABs. This study investigated the relationship between CAB use, alcohol misuse, and person-level characteristics including impulsive personality traits, delayed reward discounting, and behavioral economic demand for alcohol use. Participants were 273 regularly drinking undergraduate students. Frequency of CAB use was assessed over the past month. A multidimensional assessment of impulsivity included the UPPS-P questionnaire and a validated, questionnaire-based measure of delayed reward discounting. Demand was assessed via a hypothetical alcohol purchase task. Frequency of CAB consumption was significantly higher in males compared to females and was also associated with higher impulsivity on the majority of the UPPS-P subscales, steeper delayed reward discounting, and greater demand for alcohol. Significant correlations between CAB use and both alcohol demand and lack of premeditation remained present after including level of alcohol misuse in partial correlations. In a hierarchical linear regression incorporating demographic, demand, and impulsivity variables, CAB frequency continued to be a significant predictor of hazardous alcohol use. These results suggest that although there are significant associations between CAB consumption and gender, impulsivity, and alcohol demand, CAB use continues to be associated with alcohol misuse after controlling for these variables. PMID:24364537

Alcohol prevention strategies on college campuses and student alcohol abuse and related problems.

PubMed

Ringwalt, Christopher L; Paschall, Mallie J; Gitelman, Amy M

2011-01-01

This study examined the relationship between colleges' alcohol abuse prevention strategies and students' alcohol abuse and related problems. Alcohol prevention coordinators and first year students in 22 colleges reported whether their schools were implementing 48 strategies in six domains, and students (N = 2041) completed another survey concerning their use of alcohol and related consequences. Colleges were most likely to prevent alcohol use in public places on campus and the delivery and use of kegs. Four alcohol prevention domains were inversely associated with at least one of five outcomes related to student alcohol abuse or related consequences, and the alcohol policy and enforcement domain was inversely associated with all outcomes. Colleges should pay particular attention to strategies related to policy and enforcement.

Impact of alcohol-promoting and alcohol-warning advertisements on alcohol consumption, affect, and implicit cognition in heavy-drinking young adults: A laboratory-based randomized controlled trial.

PubMed

Stautz, Kaidy; Frings, Daniel; Albery, Ian P; Moss, Antony C; Marteau, Theresa M

2017-02-01

There is sparse evidence regarding the effect of alcohol-advertising exposure on alcohol consumption among heavy drinkers. This study aimed to assess the immediate effects of alcohol-promoting and alcohol-warning video advertising on objective alcohol consumption in heavy-drinking young adults, and to examine underlying processes. Between-participants randomized controlled trial with three conditions. Two hundred and four young adults (aged 18-25) who self-reported as heavy drinkers were randomized to view one of three sets of 10 video advertisements that included either (1) alcohol-promoting, (2) alcohol-warning, or (3) non-alcohol advertisements. The primary outcome was the proportion of alcoholic beverages consumed in a sham taste test. Affective responses to advertisements, implicit alcohol approach bias, and alcohol attentional bias were assessed as secondary outcomes and possible mediators. Typical alcohol consumption, Internet use, and television use were measured as covariates. There was no main effect of condition on alcohol consumption. Participants exposed to alcohol-promoting advertisements showed increased positive affect and an increased approach/reduced avoidance bias towards alcohol relative to those exposed to non-alcohol advertisements. There was an indirect effect of exposure to alcohol-warning advertisements on reduced alcohol consumption via negative affect experienced in response to these advertisements. Restricting alcohol-promoting advertising could remove a potential influence on positive alcohol-related emotions and cognitions among heavy-drinking young adults. Producing alcohol-warning advertising that generates negative emotion may be an effective strategy to reduce alcohol consumption. Statement of contribution What is already known on this subject? Exposure to alcohol advertising has immediate and distal effects on alcohol consumption. There is some evidence that effects may be larger in heavy drinkers. Alcohol-warning advertising has

Racial/ethnic differences in the influence of cultural values, alcohol resistance self-efficacy, and alcohol expectancies on risk for alcohol initiation.

PubMed

Shih, Regina A; Miles, Jeremy N V; Tucker, Joan S; Zhou, Annie J; D'Amico, Elizabeth J

2012-09-01

Prior research has reported racial/ethnic differences in the early initiation of alcohol use, suggesting that cultural values that are central to specific racial/ethnic groups may be influencing these differences. This 1-year longitudinal study examines associations between two types of cultural values, parental respect (honor for one's parents) and familism (connectedness with family), both measured at baseline, and subsequent alcohol initiation in a sample of 6,054 (approximately 49% male, 57% Hispanic, 22% Asian, 18% non-Hispanic White, and 4% non-Hispanic Black) middle school students in Southern California. We tested whether the associations of cultural values with alcohol initiation could be explained by baseline measures of alcohol resistance self-efficacy (RSE) and alcohol expectancies. We also explored whether these pathways differed by race/ethnicity. In the full sample, adolescents with higher parental respect were less likely to initiate alcohol use, an association that was partially explained by higher RSE and fewer positive alcohol expectancies. Familism was not significantly related to alcohol initiation. Comparing racial/ethnic groups, higher parental respect was protective against alcohol initiation for Whites and Asians, but not Blacks or Hispanics. There were no racial/ethnic differences in the association between familism and alcohol initiation. Results suggest that cultural values are important factors in the decision to use alcohol and these values appear to operate in part, by influencing alcohol positive expectancies and RSE. Interventions that focus on maintaining strong cultural values and building strong bonds between adolescents and their families may help reduce the risk of alcohol initiation. PsycINFO Database Record (c) 2012 APA, all rights reserved.

In Focus: Alcohol and Alcoholism Audiovisual Guide.

ERIC Educational Resources Information Center

National Clearinghouse for Alcohol Information (DHHS), Rockville, MD.

This guide reviews audiovisual materials currently available on alcohol abuse and alcoholism. An alphabetical index of audiovisual materials is followed by synopses of the indexed materials. Information about the intended audience, price, rental fee, and distributor is included. This guide also provides a list of publications related to media…

Alcohol Consumption and Harm among Adolescents in Sweden: Is Smuggled Alcohol More Harmful?

ERIC Educational Resources Information Center

Svensson, Johan

2012-01-01

As a consequence of Sweden joining the European Union, privately imported alcohol is increasingly sold within illegal contexts (i.e., smuggled alcohol). One implication of the smuggled alcohol is that alcohol becomes more available to underage drinkers. In the Swedish debate, smuggled alcohol has been formulated as a youth problem. The aim of this…

The Cognitive and Behavioural Impact of Alcohol Promoting and Alcohol Warning Advertisements: An Experimental Study.

PubMed

Brown, Kyle G; Stautz, Kaidy; Hollands, Gareth J; Winpenny, Eleanor M; Marteau, Theresa M

2016-05-01

To assess the immediate effect of alcohol promoting and alcohol warning advertisements on implicit and explicit attitudes towards alcohol and on alcohol seeking behaviour. We conducted a between-participants online experiment in which participants were randomly assigned to view one of three sets of advertisements: (a) alcohol promoting, (b) alcohol warning, or (c) unrelated to alcohol. A total of 373 participants (59.5% female) aged 18-40 (M = 28.03) living in the UK were recruited online through a research agency. Positive and negative implicit attitudes and explicit attitudes towards alcohol were assessed before and after advertisements were viewed. Alcohol seeking behaviour was measured by participants' choice of either an alcohol-related or non-alcohol-related voucher offered ostensibly as a reward for participation. Self-reported past week alcohol consumption was also recorded. There were no main effects on any of the outcome measures. In heavier drinkers, viewing alcohol promoting advertisements increased positive implicit attitudes (standardized beta = 0.15, P = 0.04) and decreased negative implicit attitudes (standardized beta = -0.17, P = 0.02). In heavier drinkers, viewing alcohol warning advertisements decreased negative implicit attitudes (standardized beta = -0.19, P = 0.01). Viewing alcohol promoting advertisements has a cognitive impact on heavier drinkers, increasing positive and reducing negative implicit attitudes towards alcohol. Viewing alcohol warning advertisements reduces negative implicit attitudes towards alcohol in heavier drinkers, suggestive of a reactance effect. © The Author 2015. Medical Council on Alcohol and Oxford University Press.

Caffeinated Alcoholic Beverages – An Emerging Trend in Alcohol Abuse

PubMed Central

Franklin, Kelle M; Hauser, Sheketha R; Bell, Richard L.; Engleman, Eric A

2014-01-01

Alcohol use disorders are pervasive in society and their impact affects quality of life, morbidity and mortality, as well as individual productivity. Alcohol has detrimental effects on an individual’s physiology and nervous system, and is associated with disorders of many organ and endocrine systems impacting an individual’s health, behavior, and ability to interact with others. Youth are particularly affected. Unfortunately, adolescent usage also increases the probability for a progression to dependence. Several areas of research indicate that the deleterious effects of alcohol abuse may be exacerbated by mixing caffeine with alcohol. Some behavioral evidence suggests that caffeine increases alcohol drinking and binge drinking episodes, which in turn can foster the development of alcohol dependence. As a relatively new public health concern, the epidemiological focus has been to establish a need for investigating the effects of caffeinated alcohol. While the trend of co-consuming these substances is growing, knowledge of the central mechanisms associated with caffeinated ethanol has been lacking. Research suggests that caffeine and ethanol can have additive or synergistic pharmacological actions and neuroadaptations, with the adenosine and dopamine systems in particular implicated. However, the limited literature on the central effects of caffeinated ethanol provides an impetus to increase our knowledge of the neuroadaptive effects of this combination and their impact on cognition and behavior. Research from our laboratories indicates that an established rodent animal model of alcoholism can be extended to investigate the acute and chronic effects of caffeinated ethanol. PMID:25419478

A UK student survey investigating the effects of consuming alcohol mixed with energy drinks on overall alcohol consumption and alcohol-related negative consequences.

PubMed

Johnson, Sean J; Alford, Chris; Stewart, Karina; Verster, Joris C

2016-12-01

Previous research reported positive associations between alcohol mixed with energy drink (AMED) consumption and overall alcohol consumption. However, results were largely based on between-subjects comparisons comparing AMED consumers with alcohol-only (AO) consumers, and therefore cannot sufficiently control for differences in personal characteristics between these groups. In order to determine whether AMED consumers drink more alcohol on occasions they consume AMED compared to those when they drink AO additional within-subjects comparisons are required. Therefore, this UK student survey assessed both alcohol consumption and alcohol-related negative consequences when consumed alone and when mixed with energy drinks, using a within-subject design. A total of 1873 students completed the survey, including 732 who consumed AMED. It was found that AMED consumers drank significantly less alcohol when they consumed AMED compared to when they drank AO (p < 0.001). In line with reduced alcohol consumption significantly fewer negative alcohol-related consequences were reported on AMED occasions compared to AO occasions (p < 0.001). These findings suggest that mixing alcohol with energy drinks does not increase total alcohol consumption or alcohol-related negative consequences.

Assessing the impacts of Saskatchewan's minimum alcohol pricing regulations on alcohol-related crime.

PubMed

Stockwell, Tim; Zhao, Jinhui; Sherk, Adam; Callaghan, Russell C; Macdonald, Scott; Gatley, Jodi

2017-07-01

Saskatchewan's introduction in April 2010 of minimum prices graded by alcohol strength led to an average minimum price increase of 9.1% per Canadian standard drink (=13.45 g ethanol). This increase was shown to be associated with reduced consumption and switching to lower alcohol content beverages. Police also informally reported marked reductions in night-time alcohol-related crime. This study aims to assess the impacts of changes to Saskatchewan's minimum alcohol-pricing regulations between 2008 and 2012 on selected crime events often related to alcohol use. Data were obtained from Canada's Uniform Crime Reporting Survey. Auto-regressive integrated moving average time series models were used to test immediate and lagged associations between minimum price increases and rates of night-time and police identified alcohol-related crimes. Controls were included for simultaneous crime rates in the neighbouring province of Alberta, economic variables, linear trend, seasonality and autoregressive and/or moving-average effects. The introduction of increased minimum-alcohol prices was associated with an abrupt decrease in night-time alcohol-related traffic offences for men (-8.0%, P < 0.001), but not women. No significant immediate changes were observed for non-alcohol-related driving offences, disorderly conduct or violence. Significant monthly lagged effects were observed for violent offences (-19.7% at month 4 to -18.2% at month 6), which broadly corresponded to lagged effects in on-premise alcohol sales. Increased minimum alcohol prices may contribute to reductions in alcohol-related traffic-related and violent crimes perpetrated by men. Observed lagged effects for violent incidents may be due to a delay in bars passing on increased prices to their customers, perhaps because of inventory stockpiling. [Stockwell T, Zhao J, Sherk A, Callaghan RC, Macdonald S, Gatley J. Assessing the impacts of Saskatchewan's minimum alcohol pricing regulations on alcohol

Alcohol and the law.

PubMed

Karasov, Ariela O; Ostacher, Michael J

2014-01-01

Society has had an interest in controlling the production, distribution, and use of alcohol for millennia. The use of alcohol has always had consequences, be they positive or negative, and the role of government in the regulation of alcohol is now universal. This is accomplished at several levels, first through controls on production, importation, distribution, and use of alcoholic beverages, and second, through criminal laws, the aim of which is to address the behavior of users themselves. A number of interventions and policies reduce alcohol-related consequences to society by regulating alcohol pricing, targeting alcohol-impaired driving, and limiting alcohol availability. The legal system defines criminal responsibility in the context of alcohol use, as an enormous percentage of violent crime and motor death is associated with alcohol intoxication. In recent years, recovery-oriented policies have aimed to expand social supports for recovery and to improve access to treatment for substance use disorders within the criminal justice system. The Affordable Care Act, also know as "ObamaCare," made substantial changes to access to substance abuse treatment by mandating that health insurance include services for substance use disorders comparable to coverage for medical and surgical treatments. Rather than a simplified "war on drugs" approach, there appears to be an increasing emphasis on evidence-based policy development that approaches alcohol use disorders with hope for treatment and prevention. This chapter focuses on alcohol and the law in the United States. © 2014 Elsevier B.V. All rights reserved.

Quantitative electroencephalography analysis in university students with hazardous alcohol consumption, but not alcohol dependence.

PubMed

Núñez-Jaramillo, Luis; Vega-Perera, Paulo; Ramírez-Lugo, Leticia; Reyes-López, Julián V; Santiago-Rodríguez, Efraín; Herrera-Morales, Wendy V

2015-07-08

Hazardous alcohol consumption is a pattern of consumption that leads to a higher risk of harmful consequences either for the user or for others. This pattern of alcohol consumption has been linked to risky behaviors, accidents, and injuries. Individuals with hazardous alcohol consumption do not necessarily present alcohol dependence; thus, a study of particular neurophysiological correlates of this alcohol consumption pattern needs to be carried out in nondependent individuals. Here, we carried out a quantitative electroencephalography analysis in health sciences university students with hazardous alcohol consumption, but not alcohol dependence (HAC), and control participants without hazardous alcohol consumption or alcohol dependence (NHAC). We analyzed Absolute Power (AP), Relative Power (RP), and Mean Frequency (MF) for beta and theta frequency bands under both eyes closed and eyes open conditions. We found that participants in the HAC group presented higher beta AP at centroparietal region, as well as lower beta MF at frontal and centroparietal regions in the eyes closed condition. Interestingly, participants did not present any change in theta activity (AP, RP, or MF), whereas previous reports indicate an increase in theta AP in alcohol-dependent individuals. Our results partially resemble those found in alcohol-dependent individuals, although are not completely identical, suggesting a possible difference in the underlying neuronal mechanism behind alcohol dependence and hazardous alcohol consumption. Similarities could be explained considering that both hazardous alcohol consumption and alcohol dependence are manifestations of behavioral disinhibition.

Multiple mechanisms influencing the relationship between alcohol consumption and peer alcohol use.

PubMed

Edwards, Alexis C; Maes, Hermine H; Prescott, Carol A; Kendler, Kenneth S

2015-02-01

Alcohol consumption is typically correlated with the alcohol use behaviors of one's peers. Previous research has suggested that this positive relationship could be due to social selection, social influence, or a combination of both processes. However, few studies have considered the role of shared genetic and environmental influences in conjunction with causal processes. This study uses data from a sample of male twins (N = 1,790) who provided retrospective reports of their own alcohol consumption and their peers' alcohol-related behaviors, from adolescence into young adulthood (ages 12 to 25). Structural equation modeling was employed to compare 3 plausible models of genetic and environmental influences on the relationship between phenotypes over time. Model fitting indicated that one's own alcohol consumption and the alcohol use of one's peers are related through both genetic and shared environmental factors and through unique environmental causal influences. The relative magnitude of these factors, and their contribution to covariation, changed over time, with genetic factors becoming more meaningful later in development. Peers' alcohol use behaviors and one's own alcohol consumption are related through a complex combination of genetic and environmental factors that act via correlated factors and the complementary causal mechanisms of social selection and influence. Understanding these processes can inform risk assessment as well as improve our ability to model the development of alcohol use. Copyright © 2015 by the Research Society on Alcoholism.

Alcohol use and interpersonal violence: alcohol detected in homicide victims.

PubMed Central

Goodman, R A; Mercy, J A; Loya, F; Rosenberg, M L; Smith, J C; Allen, N H; Vargas, L; Kolts, R

1986-01-01

To characterize the relationship between alcohol use and homicide victimization, we used data from the Los Angeles City Police Department and the Los Angeles Medical Examiner's Office to study 4,950 victims of criminal homicides in Los Angeles in the period 1970-79. Alcohol was detected in the blood of 1,883 (46 per cent) of the 4,092 victims who were tested. In 30 per cent of those tested, the blood alcohol level was greater than or equal to 100 mg/100 ml, the level of legal intoxication in most states. Blood alcohol was present most commonly in victims who were male, young, and Latino, categories where rates have been increasing at an alarming pace. Alcohol was also detected most commonly in victims killed during weekends, when homicides occurred in bars or restaurants, when homicides resulted from physical fights or verbal arguments, when victims were friends or acquaintances of offenders, and when homicides resulted from stabbings. The evidence for alcohol use by homicide victims focuses attention on the need for controlled epidemiologic studies of the role played by alcohol as a risk factor in homicide and on the importance of considering situational variables in developing approaches to homicide prevention. PMID:3946695

THE RELATIONSHIP BETWEEN REASONS FOR DRINKING ALCOHOL AND ALCOHOL CONSUMPTION: AN INTERACTIONAL APPROACH

PubMed Central

ABBEY, ANTONIA; SMITH, MARY JO; SCOTT, RICHARD O.

2015-01-01

Two motives for alcohol consumption have been emphasized in the etiological and the reasons-for-drinking literature: (a) people drink alcohol to cope with stress, and (b) people drink alcohol because of social influences. There is support for both of these hypotheses, but the results are usually modest and most authors agree that more complex theories of alcohol consumption are needed. This study examined the interactional effects of reasons for drinking alcohol and situational factors on alcohol consumption. Standardized telephone interviews were conducted with 781 randomly selected Michigan drinkers. Hierarchical multiple regression analyses indicated that gender, friends’ alcohol consumption, coping, and social motives for drinking were significant predictors of study participants’ alcohol consumption. As predicted, there was a significant interaction between drinking to cope with stress and perceived stress, and there was also a significant interaction between drinking for social reasons and friends’ alcohol consumption. Similarities and differences in the results for women, men, Blacks, and Whites are described. PMID:8178704

Effect of memantine on cue-induced alcohol craving in recovering alcohol-dependent patients.

PubMed

Krupitsky, Evgeny M; Neznanova, Olga; Masalov, Dimitry; Burakov, Andrey M; Didenko, Tatyana; Romanova, Tatyana; Tsoy, Marina; Bespalov, Anton; Slavina, Tatyana Y; Grinenko, Alexander A; Petrakis, Ismene L; Pittman, Brian; Gueorguieva, Ralitza; Zvartau, Edwin E; Krystal, John H

2007-03-01

Ethanol blocks N-methyl-d-aspartic acid (NMDA) glutamate receptors. Increased NMDA receptor function may contribute to motivational disturbances that contribute to alcoholism. The authors assessed whether the NMDA receptor antagonist memantine reduces cue-induced alcohol craving and produces ethanol-like subjective effects. Thirty-eight alcohol-dependent inpatients participated in three daylong testing sessions in a randomized order under double-blind conditions. On each test day, subjects received 20 mg of memantine, 40 mg of memantine, or placebo, and subjective responses to treatment were assessed. The level of alcohol craving was assessed before and after exposure to an alcohol cue. Memantine did not stimulate alcohol craving before exposure to an alcohol cue, and it attenuated alcohol cue-induced craving in a dose-related fashion. It produced dose-related ethanol-like effects without adverse cognitive or behavioral effects. These data support further exploration of whether well-tolerated NMDA receptor antagonists might have a role in the treatment of alcoholism.

Monkey alcohol tissue research resource: banking tissues for alcohol research.

PubMed

Daunais, James B; Davenport, April T; Helms, Christa M; Gonzales, Steven W; Hemby, Scott E; Friedman, David P; Farro, Jonathan P; Baker, Erich J; Grant, Kathleen A

2014-07-01

An estimated 18 million adults in the United States meet the clinical criteria for diagnosis of alcohol abuse or alcoholism, a disorder ranked as the third leading cause of preventable death. In addition to brain pathology, heavy alcohol consumption is comorbid with damage to major organs including heart, lungs, liver, pancreas, and kidneys. Much of what is known about risk for and consequences of heavy consumption derive from rodent or retrospective human studies. The neurobiological effects of chronic intake in rodent studies may not easily translate to humans due to key differences in brain structure and organization between species, including a lack of higher-order cognitive functions, and differences in underlying prefrontal cortical neural structures that characterize the primate brain. Further, rodents do not voluntarily consume large quantities of ethanol (EtOH) and they metabolize it more rapidly than primates. The basis of the Monkey Alcohol Tissue Research Resource (MATRR) is that nonhuman primates, specifically monkeys, show a range of drinking excessive amounts of alcohol (>3.0 g/kg or a 12 drink equivalent per day) over long periods of time (12 to 30 months) with concomitant pathological changes in endocrine, hepatic, and central nervous system (CNS) processes. The patterns and range of alcohol intake that monkeys voluntarily consume parallel what is observed in humans with alcohol use disorders and the longitudinal experimental design spans stages of drinking from the EtOH-naïve state to early exposure through chronic abuse. Age- and sex-matched control animals self-administer an isocaloric solution under identical operant procedures. The MATRR is a unique postmortem tissue bank that provides CNS and peripheral tissues, and associated bioinformatics from monkeys that self-administer EtOH using a standardized experimental paradigm to the broader alcohol research community. This resource provides a translational platform from which we can better

The effect of prior alcohol consumption on the ataxic response to alcohol in high-alcohol preferring mice

PubMed Central

Fritz, Brandon M.; Boehm, Stephen L.

2014-01-01

We have previously shown that ethanol-naïve high-alcohol preferring (HAP) mice, genetically predis-posed to consume large quantities of alcohol, exhibited heightened sensitivity and more rapid acute functional tolerance (AFT) to alcohol-induced ataxia compared to low-alcohol preferring mice. The goal of the present study was to evaluate the effect of prior alcohol self-administration on these responses in HAP mice. Naïve male and female adult HAP mice from the second replicate of selection (HAP2) underwent 18 days of 24-h, 2-bottle choice drinking for 10% ethanol vs. water, or water only. After 18 days of fluid access, mice were tested for ataxic sensitivity and rapid AFT following a 1.75 g/kg injection of ethanol on a static dowel apparatus in Experiment 1. In Experiment 2, a separate group of mice was tested for more protracted AFT development using a dual-injection approach where a second, larger (2.0 g/kg) injection of ethanol was given following the initial recovery of performance on the task. HAP2 mice that had prior access to alcohol exhibited a blunted ataxic response to the acute alcohol challenge, but this pre-exposure did not alter rapid within-session AFT capacity in Experiment 1 or more protracted AFT capacity in Experiment 2. These findings suggest that the typically observed increase in alcohol consumption in these mice may be influenced by ataxic functional tolerance development, but is not mediated by a greater capacity for ethanol exposure to positively influence within-session ataxic tolerance. PMID:25454537

A Multidimensional Model of Mothers’ Perceptions of Parent Alcohol Socialization and Adolescent Alcohol Misuse

PubMed Central

Ennett, Susan T.; Jackson, Christine; Cole, Veronica T.; Haws, Susan; Foshee, Vangie A.; Reyes, Heathe Luz McNaughton; Burns, Alison Reimuller; Cox, Melissa J.; Cai, Li

2015-01-01

We assessed a multidimensional model of parent alcohol socialization in which key socialization factors were considered simultaneously to identify combinations of factors that increase or decrease risk for development of adolescent alcohol misuse. Of interest was the interplay between putative risk and protective factors, such as whether the typically detrimental effects on youth drinking of parenting practices tolerant of some adolescent alcohol use are mitigated by an effective overall approach to parenting and parental modeling of modest alcohol use. The sample included 1,530 adolescents and their mothers; adolescents’ mean age was 13.0 (SD = .99) at the initial assessment. Latent profile analysis was conducted of mothers’ reports of their attitude toward teen drinking, alcohol-specific parenting practices, parental alcohol use and problem use, and overall approach to parenting. The profiles were used to predict trajectories of adolescent alcohol misuse from early to middle adolescence. Four profiles were identified: two profiles reflected conservative alcohol-specific parenting practices and two reflected alcohol-tolerant practices, all in the context of other attributes. Alcohol misuse accelerated more rapidly from grade 6 through 10 in the two alcohol-tolerant compared with conservative profiles. Results suggest that maternal tolerance of some youth alcohol use, even in the presence of dimensions of an effective parenting style and low parental alcohol use and problem use, is not an effective strategy for reducing risky adolescent alcohol use. PMID:26415053

Quantifying alcohol-related emergency admissions in a UK tertiary referral hospital: a cross-sectional study of chronic alcohol dependency and acute alcohol intoxication

PubMed Central

Vardy, J; Keliher, T; Fisher, J; Ritchie, F; Bell, C; Chekroud, M; Clarey, F; Blackwood, L; Barry, L; Paton, E; Clark, A; Connelly, R

2016-01-01

Objectives Alcohol is responsible for a proportion of emergency admissions to hospital, with acute alcohol intoxication and chronic alcohol dependency (CAD) implicated. This study aims to quantify the proportion of hospital admissions through our emergency department (ED) which were thought by the admitting doctor to be (largely or partially) a result of alcohol consumption. Setting ED of a UK tertiary referral hospital. Participants All ED admissions occurring over 14 weeks from 1 September to 8 December 2012. Data obtained for 5497 of 5746 admissions (95.67%). Primary outcome measures Proportion of emergency admissions related to alcohol as defined by the admitting ED clinician. Secondary outcome measures Proportion of emergency admissions due to alcohol diagnosed with acute alcohol intoxication or CAD according to ICD-10 criteria. Results 1152 (21.0%, 95% CI 19.9% to 22.0%) of emergency admissions were thought to be due to alcohol. 74.6% of patients admitted due to alcohol had CAD, and significantly greater than the 26.4% with ‘Severe’ or ‘Very Severe’ acute alcohol intoxication (p<0.001). Admissions due to alcohol differed to admissions not due to alcohol being on average younger (45 vs 56 years, p<0.001) more often male (73.4% vs 45.1% males, p<0.001) and more likely to have a diagnosis synonymous with alcohol or related to recreational drug use, pancreatitis, deliberate self-harm, head injury, gastritis, suicidal ideation, upper gastrointestinal bleeds or seizures (p<0.001). An increase in admissions due to alcohol on Saturdays reflects a surge in admissions with acute alcohol intoxication above the weekly average (p=0.003). Conclusions Alcohol was thought to be implicated in 21% of emergency admissions in this cohort. CAD is responsible for a significantly greater proportion of admissions due to alcohol than acute intoxication. Interventions designed to reduce alcohol-related admissions must incorporate measures to tackle CAD. PMID:27324707

Quantifying alcohol-related emergency admissions in a UK tertiary referral hospital: a cross-sectional study of chronic alcohol dependency and acute alcohol intoxication.

PubMed

Vardy, J; Keliher, T; Fisher, J; Ritchie, F; Bell, C; Chekroud, M; Clarey, F; Blackwood, L; Barry, L; Paton, E; Clark, A; Connelly, R

2016-06-20

Alcohol is responsible for a proportion of emergency admissions to hospital, with acute alcohol intoxication and chronic alcohol dependency (CAD) implicated. This study aims to quantify the proportion of hospital admissions through our emergency department (ED) which were thought by the admitting doctor to be (largely or partially) a result of alcohol consumption. ED of a UK tertiary referral hospital. All ED admissions occurring over 14 weeks from 1 September to 8 December 2012. Data obtained for 5497 of 5746 admissions (95.67%). Proportion of emergency admissions related to alcohol as defined by the admitting ED clinician. Proportion of emergency admissions due to alcohol diagnosed with acute alcohol intoxication or CAD according to ICD-10 criteria. 1152 (21.0%, 95% CI 19.9% to 22.0%) of emergency admissions were thought to be due to alcohol. 74.6% of patients admitted due to alcohol had CAD, and significantly greater than the 26.4% with 'Severe' or 'Very Severe' acute alcohol intoxication (p<0.001). Admissions due to alcohol differed to admissions not due to alcohol being on average younger (45 vs 56 years, p<0.001) more often male (73.4% vs 45.1% males, p<0.001) and more likely to have a diagnosis synonymous with alcohol or related to recreational drug use, pancreatitis, deliberate self-harm, head injury, gastritis, suicidal ideation, upper gastrointestinal bleeds or seizures (p<0.001). An increase in admissions due to alcohol on Saturdays reflects a surge in admissions with acute alcohol intoxication above the weekly average (p=0.003). Alcohol was thought to be implicated in 21% of emergency admissions in this cohort. CAD is responsible for a significantly greater proportion of admissions due to alcohol than acute intoxication. Interventions designed to reduce alcohol-related admissions must incorporate measures to tackle CAD. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

Salivary alcohol dehydrogenase in non-smoking and smoking alcohol-dependent persons.

PubMed

Waszkiewicz, Napoleon; Jelski, Wojciech; Zalewska, Anna; Szulc, Agata; Szmitkowski, Maciej; Zwierz, Krzysztof; Szajda, Sławomir Dariusz

2014-09-01

Increasing attention to the importance of saliva testing is not surprising because smoking and alcohol drinking act synergistically on oral tissues, and their metabolite levels, e.g., acetaldehyde, are much higher in saliva than in blood. The activity of salivary alcohol dehydrogenase (ADH) comes from oral microbiota, mucosa, and salivary glands. The purpose of this study was to investigate the involvement of ADH in the oral health pathology of smoking (AS) and non-smoking (ANS) alcohol-dependent males. The results indicated that the AS group had a more significant and longer duration (until the 30th day of alcohol abstinence) decrease in ADH activity and output than the ANS group (until the 15th day of alcohol abstinence) compared to controls (social drinkers; C). The decreased salivary flow (SF) in alcoholics was observed longer in the ANS group (until the 30th day of alcohol abstinence), whereas in the AS group SF normalized at the 15th day, probably due to the irritating effect of tobacco smoke on the oral mucosa. Because saliva was centrifuged to remove cells and debris (including microbial cells), the detected salivary ADH activity was derived from salivary glands and/or oral mucosa. A more profound and longer decrease in ADH activity/output in smoking than non-smoking alcoholics was likely due to the damaged salivary glands and/or oral mucosa, caused by the synergistic effect of alcohol drinking and smoking. The lower values of salivary ADH in smoking than non-smoking alcoholics might also be partly due to the reversed/inhibited ADH reaction by high levels of accumulated acetaldehyde. Copyright © 2014 Elsevier Inc. All rights reserved.

Alcohol consumption and burden of disease in the Americas in 2012: implications for alcohol policy.

PubMed

Shield, Kevin D; Monteiro, Maristela; Roerecke, Michael; Smith, Blake; Rehm, Jürgen

2015-12-01

To describe the volume and patterns of alcohol consumption up to and including 2012, and to estimate the burden of disease attributable to alcohol consumption as measured in deaths and disability-adjusted life years (DALYs) lost in the Americas in 2012. Measures of alcohol consumption were obtained from the World Health Organization (WHO) Global Information System on Alcohol and Health (GISAH). The burden of alcohol consumption was estimated in both deaths and DALYs lost based on mortality data obtained from WHO, using alcohol-attributable fractions. Regional groupings for the Americas were based on the WHO classifications for 2004 (according to child and adult mortality). Regional variations were observed in the overall volume of alcohol consumed, the proportion of the alcohol market attributable to unrecorded alcohol consumption, drinking patterns, prevalence of drinking, and prevalence of heavy episodic drinking, with inhabitants of the Americas consuming more alcohol (8.4 L of pure alcohol per adult in 2012) compared to the world average. The Americas also experienced a high burden of disease attributable to alcohol consumption (4.7% of all deaths and 6.7% of all DALYs lost), especially in terms of injuries attributable to alcohol consumption. Alcohol is consumed in a harmful manner in the Americas, leading to a high burden of disease, especially in terms of injuries. New cost-effective alcohol policies, such as increasing alcohol taxation, increasing the minimum legal age to purchase alcohol, and decreasing the maximum legal blood alcohol content while driving, should be implemented to decrease the harmful consumption of alcohol and the resulting burden of disease.

The Cognitive and Behavioural Impact of Alcohol Promoting and Alcohol Warning Advertisements: An Experimental Study

PubMed Central

Brown, Kyle G.; Stautz, Kaidy; Hollands, Gareth J.; Winpenny, Eleanor M.; Marteau, Theresa M.

2016-01-01

Aims To assess the immediate effect of alcohol promoting and alcohol warning advertisements on implicit and explicit attitudes towards alcohol and on alcohol seeking behaviour. Methods We conducted a between-participants online experiment in which participants were randomly assigned to view one of three sets of advertisements: (a) alcohol promoting, (b) alcohol warning, or (c) unrelated to alcohol. A total of 373 participants (59.5% female) aged 18–40 (M = 28.03) living in the UK were recruited online through a research agency. Positive and negative implicit attitudes and explicit attitudes towards alcohol were assessed before and after advertisements were viewed. Alcohol seeking behaviour was measured by participants' choice of either an alcohol-related or non-alcohol-related voucher offered ostensibly as a reward for participation. Self-reported past week alcohol consumption was also recorded. Results There were no main effects on any of the outcome measures. In heavier drinkers, viewing alcohol promoting advertisements increased positive implicit attitudes (standardized beta = 0.15, P = 0.04) and decreased negative implicit attitudes (standardized beta = −0.17, P = 0.02). In heavier drinkers, viewing alcohol warning advertisements decreased negative implicit attitudes (standardized beta = −0.19, P = 0.01). Conclusions Viewing alcohol promoting advertisements has a cognitive impact on heavier drinkers, increasing positive and reducing negative implicit attitudes towards alcohol. Viewing alcohol warning advertisements reduces negative implicit attitudes towards alcohol in heavier drinkers, suggestive of a reactance effect. PMID:26391367

The Neurobiology of Alcohol Consumption and Alcoholism: An Integrative History1

PubMed Central

Tabakoff, Boris; Hoffman, Paula L.

2013-01-01

Studies of the neurobiological predisposition to consume alcohol (ethanol) and to transition to uncontrolled drinking behavior (alcoholism), as well as studies of the effects of alcohol on brain function, started a logarithmic growth phase after the repeal of the 18th Amendment to the United States Constitution. Although the early studies were primitive by current technological standards, they clearly demonstrated the effects of alcohol on brain structure and function, and by the end of the 20th century left little doubt that alcoholism is a “disease” of the brain. This review traces the history of developments in the understanding of ethanol’s effects on the most prominent inhibitory and excitatory systems of brain (GABA and glutamate neurotransmission). This neurobiological information is integrated with knowledge of ethanol’s actions on other neurotransmitter systems to produce an anatomical and functional map of ethanol’s properties. Our intent is limited in scope, but is meant to provide context and integration of the actions of ethanol on the major neurobiologic systems which produce reinforcement for alcohol consumption and changes in brain chemistry that lead to addiction. The developmental history of neurobehavioral theories of the transition from alcohol drinking to alcohol addiction is presented and juxtaposed to the neurobiological findings. Depending on one’s point of view, we may, at this point in history, know more, or less, than we think we know about the neurobiology of alcoholism. PMID:24141171

75 FR 42450 - National Institute on Alcohol Abuse and Alcoholism; Notice of Closed Meeting

Federal Register 2010, 2011, 2012, 2013, 2014

2010-07-21

... Alcohol Abuse and Alcoholism; Notice of Closed Meeting Pursuant to section 10(d) of the Federal Advisory... and Alcoholism Initial Review Group; Epidemiology, Prevention and Behavior Research Review... Alcohol Abuse and Alcoholism, Office of Extramural Activities, Extramural Project Review Branch, 5635...

Impulsivity and alcohol demand in relation to combined alcohol and caffeine use.

PubMed

Amlung, Michael; Few, Lauren R; Howland, Jonathan; Rohsenow, Damaris J; Metrik, Jane; MacKillop, James

2013-12-01

Problematic alcohol use among college students continues to be a prominent concern in the United States, including the growing trend of consuming caffeinated alcoholic beverages (CABs). Epidemiologically, CAB use is associated with incremental risks from drinking, although these relationships could be due to common predisposing factors rather than specifically due to CABs. This study investigated the relationship between CAB use, alcohol misuse, and person-level characteristics, including impulsive personality traits, delayed reward discounting, and behavioral economic demand for alcohol use. Participants were 273 regularly drinking undergraduate students. Frequency of CAB use was assessed over the past month. A multidimensional assessment of impulsivity included the UPPS-P questionnaire, which measures positive and negative urgency, premeditation (lack thereof), perseverance (lack thereof), and sensation seeking (Lynam, Smith, Whiteside, & Cyders, 2007), and a validated questionnaire-based measure of delayed reward discounting. Demand was assessed via a hypothetical alcohol purchase task. Frequency of CAB consumption was significantly higher in men than in women and was also associated with higher impulsivity on the majority of the UPPS-P subscales, steeper delayed reward discounting, and greater demand for alcohol. Significant correlations between CAB use and both alcohol demand and lack of premeditation remained present after including level of alcohol misuse in partial correlations. In a hierarchical linear regression incorporating demographic, demand, and impulsivity variables, CAB frequency continued to be a significant predictor of hazardous alcohol use. These results suggest that although there are significant associations between CAB consumption and gender, impulsivity, and alcohol demand, CAB use continues to be associated with alcohol misuse after controlling for these variables.

Tooth Decay in Alcohol Abusers Compared to Alcohol and Drug Abusers

PubMed Central

Dasanayake, Ananda P.; Warnakulasuriya, Saman; Harris, Colin K.; Cooper, Derek J.; Peters, Timothy J.; Gelbier, Stanley

2010-01-01

Alcohol and drug abuse are detrimental to general and oral health. Though we know the effects of these harmful habits on oral mucosa, their independent and combined effect on the dental caries experience is unknown and worthy of investigation. We compared 363 “alcohol only” abusers to 300 “alcohol and drug” abusers to test the hypothesis that various components of their dental caries experience are significantly different due to plausible sociobiological explanations. After controlling for the potential confounders, we observe that the “alcohol and drug” group had a 38% higher risk of having decayed teeth compared to the “alcohol only” group (P < .05). As expected, those who belonged to a higher social class (OR = 1.98; 95%  CI = 1.43–2.75) and drank wine (OR = 1.85; 95%  CI = 1.16–2.96) had a higher risk of having more filled teeth. We conclude that the risk of tooth decay among “alcohol only” abusers is significantly lower compared to “alcohol and drug” abusers. PMID:20379366

Clearinghouse: alcohol and poppers.

PubMed

1999-03-01

Ten articles from magazines and journals are referenced on the subjects of alcohol and poppers. Topics include alcohol consumption and HIV/AIDS-related risky sexual behavior, alcohol and drug abuse, and self-esteem, gender, and alcohol use. Contact information is provided.

Voucher-Based Reinforcement for Alcohol Abstinence Using the Ethyl-Glucuronide Alcohol Biomarker

ERIC Educational Resources Information Center

McDonell, Michael G.; Howell, Donelle N,; McPherson, Sterling; Cameron, Jennifer M.; Srebnik, Debra; Roll, John M.; Ries, Richard K.

2012-01-01

This study assessed the effects of a contingency management (CM) intervention for alcohol consumption in 10 alcohol-dependent participants. An ABCA design was used. Vouchers were provided contingent on results of ethyl glucuronide (EtG) urine tests (an alcohol biomarker with a 2-day detection period) and alcohol breath tests during the C phase.…

78 FR 21616 - National Institute on Alcohol Abuse and Alcoholism; Notice of Closed Meeting

Federal Register 2010, 2011, 2012, 2013, 2014

2013-04-11

... Alcohol Abuse and Alcoholism; Notice of Closed Meeting Pursuant to section 10(d) of the Federal Advisory... and Alcoholism Initial Review Group Clinical, Treatment and Health Services Research Review... on Alcohol Abuse & Alcoholism, National Institutes of Health, 5635 Fishers Lane, Rm. 2019, Rockville...

The moderating role of implicit alcohol-related cognitions in hazardous alcohol use

PubMed Central

Cavanagh, Lucia; Obasi, Ezemenari M.

2015-01-01

The present study applied the Go/No-Go Association Test (GNAT; Nosek & Banaji, 2001) to measure alcohol-related implicit cognitions. Additionally, it assessed the role of implicit cognitions as a potential moderator in the relationship between explicit predictors of alcohol use and hazardous drinking behavior. University undergraduate students (N = 214) completed self-report questionnaires assessing reasons for drinking and reported alcohol use. Participants also completed two GNATs assessing implicit-alcohol-related cognitions associated with attitude (good-bad) and perceived safety (safe-dangerous). As expected, participants held implicit appraisals of alcohol as ‘‘bad’’ and ‘‘dangerous’’ in the context of nonalcoholic drinks, and as ‘‘good’’ and ‘‘safe’’ in the context of licit and illicit drugs. Implicit alcohol-related cognitions moderated the relationship between drinking to cope with negative affect and hazardous drinking and drinking due to cues or craving and hazardous drinking. These findings highlight the multidimensional nature of implicit cognitions and the role of negative implicit alcohol-related associations in moderating relationships between explicit processes and subsequent alcohol use behaviors. PMID:26989352

Body mass index and alcohol consumption: family history of alcoholism as a moderator.

PubMed

Gearhardt, Ashley N; Corbin, William R

2009-06-01

Recent research suggests that excess food consumption may be conceptualized as an addictive behavior. Much of the evidence comes from neurobiological similarities between drug and food consumption. In addition, an inverse relation between alcohol consumption and body mass index (BMI) has been observed. Previous research has hypothesized that this inverse relation is attributable to competition between food and alcohol for similar neurotransmitter receptors. The current study explored this neurobiological hypothesis further by examining the influence of an indicator of biological risk associated with alcohol problems (family history of alcoholism) on the relationship between alcohol and food intake. Data from 37,259 participants in the National Epidemiologic Survey on Alcohol and Related Conditions (NESARC) were included in the study. BMI, family history of alcoholism, gender, and race/ethnicity were assessed as predictors of typical drinking frequency and estimated blood alcohol concentration (BAC). An inverse relationship between alcohol consumption and BMI was demonstrated. An attenuation of family history effects on drinking behavior was evident for obese compared to nonobese participants. The results suggest a neurobiological link between alcohol use and food consumption, consistent with theories characterizing excess food consumption as an addictive behavior. Copyright (c) 2009 APA, all rights reserved.

Alcohol-Approach Inclinations and Drinking Identity as Predictors of Behavioral Economic Demand for Alcohol

PubMed Central

Ramirez, Jason J.; Dennhardt, Ashley A.; Baldwin, Scott A.; Murphy, James G.; Lindgren, Kristen P.

2016-01-01

Behavioral economic demand curve indices of alcohol consumption reflect decisions to consume alcohol at varying costs. Although these indices predict alcohol-related problems beyond established predictors, little is known about the determinants of elevated demand. Two cognitive constructs that may underlie alcohol demand are alcohol-approach inclinations and drinking identity. The aim of this study was to evaluate implicit and explicit measures of these constructs as predictors of alcohol demand curve indices. College student drinkers (N = 223, 59% female) completed implicit and explicit measures of drinking identity and alcohol-approach inclinations at three timepoints separated by three-month intervals, and completed the Alcohol Purchase Task to assess demand at Time 3. Given no change in our alcohol-approach inclinations and drinking identity measures over time, random intercept-only models were used to predict two demand indices: Amplitude, which represents maximum hypothetical alcohol consumption and expenditures, and Persistence, which represents sensitivity to increasing prices. When modeled separately, implicit and explicit measures of drinking identity and alcohol-approach inclinations positively predicted demand indices. When implicit and explicit measures were included in the same model, both measures of drinking identity predicted Amplitude, but only explicit drinking identity predicted Persistence. In contrast, explicit measures of alcohol-approach inclinations, but not implicit measures, predicted both demand indices. Therefore, there was more support for explicit, versus implicit, measures as unique predictors of alcohol demand. Overall, drinking identity and alcohol-approach inclinations both exhibit positive associations with alcohol demand and represent potentially modifiable cognitive constructs that may underlie elevated demand in college student drinkers. PMID:27379444

78 FR 65347 - National Institute on Alcohol Abuse and Alcoholism; Notice of Closed Meeting

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2013-10-31

... Alcohol Abuse and Alcoholism; Notice of Closed Meeting Pursuant to section 10(d) of the Federal Advisory... clearly unwarranted invasion of personal privacy. Name of Committee: National Institute on Alcohol Abuse...: National Institute of Alcohol Abuse and Alcoholism, 5635 Fishers Lane (Teleconference), Rockville, MD 20855...

78 FR 41940 - National Institute on Alcohol Abuse and Alcoholism; Notice of Closed Meeting

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2013-07-12

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78 FR 55088 - National Institute on Alcohol Abuse and Alcoholism; Notice of Closed Meeting

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2013-09-09

... Alcohol Abuse and Alcoholism; Notice of Closed Meeting Pursuant to section 10(d) of the Federal Advisory... clearly unwarranted invasion of personal privacy. Name of Committee: National Institute on Alcohol Abuse... review and evaluate grant applications. Place: National Institute on Alcohol Abuse and Alcoholism, 5635...

78 FR 25755 - National Institute on Alcohol Abuse and Alcoholism; Notice of Closed Meeting

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2013-05-02

... Alcohol Abuse and Alcoholism; Notice of Closed Meeting Pursuant to section 10(d) of the Federal Advisory... clearly unwarranted invasion of personal privacy. Name of Committee: National Institute on Alcohol Abuse... Review Officer, National Institute on Alcohol Abuse and Alcoholism, 5635 Fishers Lane, Room 2109...

77 FR 54919 - National Institute on Alcohol Abuse and Alcoholism; Notice of Closed Meeting

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2012-09-06

... Alcohol Abuse and Alcoholism; Notice of Closed Meeting Pursuant to section 10(d) of the Federal Advisory... clearly unwarranted invasion of personal privacy. Name of Committee: National Institute on Alcohol Abuse... Officer, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, 5635 Fishers...

78 FR 75927 - National Institute on Alcohol Abuse and Alcoholism; Notice of Closed Meeting

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2013-12-13

... Alcohol Abuse and Alcoholism; Notice of Closed Meeting Pursuant to section 10(d) of the Federal Advisory... clearly unwarranted invasion of personal privacy. Name of Committee: National Institute on Alcohol Abuse... Institute on Alcohol Abuse and Alcoholism, 5635 Fishers Lane, (Teleconference), Rockville, MD 20852. Contact...

77 FR 43098 - National Institute on Alcohol Abuse and Alcoholism; Notice of Closed Meeting

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2012-07-23

... Alcohol Abuse and Alcoholism; Notice of Closed Meeting Pursuant to section 10(d) of the Federal Advisory... clearly unwarranted invasion of personal privacy. Name of Committee: National Institute on Alcohol Abuse and Alcoholism Special Emphasis Panel; Alcohol Center Grants--Parent Committee. Date: August 10, 2012...

75 FR 10293 - National Institute on Alcohol Abuse and Alcoholism; Notice of Closed Meeting

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2010-03-05

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77 FR 22793 - National Institute on Alcohol Abuse and Alcoholism; Notice of Closed Meeting

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2012-04-17

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75 FR 69091 - National Institute on Alcohol Abuse and Alcoholism; Notice of Closed Meeting

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2010-11-10

... Alcohol Abuse and Alcoholism; Notice of Closed Meeting Pursuant to section 10(d) of the Federal Advisory... unwarranted invasion of personal privacy. Name of Committee: National Institute on Alcohol Abuse and..., Scientific Review Officer, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health...

76 FR 49494 - National Institute on Alcohol Abuse and Alcoholism; Notice of Closed Meeting

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2011-08-10

... Alcohol Abuse and Alcoholism; Notice of Closed Meeting Pursuant to section 10(d) of the Federal Advisory... evaluation of individual intramural programs and projects conducted by the NATIONAL INSTITUTE ON ALCOHOL... evaluate Laboratory of Neuroimaging. Place: National Institutes of Alcohol Abuse and Alcoholism, 5635...

76 FR 44599 - National Institute on Alcohol Abuse and Alcoholism; Notice of Closed Meeting

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2011-07-26

... Alcohol Abuse and Alcoholism; Notice of Closed Meeting Pursuant to section 10(d) of the Federal Advisory... clearly unwarranted invasion of personal privacy. Name of Committee: National Institute on Alcohol Abuse...: Katrina L. Foster, PhD, Scientific Review Administrator, National Institutes on Alcohol Abuse & Alcoholism...

76 FR 26311 - National Institute on Alcohol Abuse and Alcoholism; Notice of Closed Meeting

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2011-05-06

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76 FR 26308 - National Institute on Alcohol Abuse and Alcoholism; Notice of Closed Meeting

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2011-05-06

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77 FR 70171 - National Institute on Alcohol Abuse and Alcoholism; Notice of Closed Meeting

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2012-11-23

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76 FR 44600 - National Institute on Alcohol Abuse and Alcoholism; Notice of Closed Meeting

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2011-07-26

... Alcohol Abuse and Alcoholism; Notice of Closed Meeting Pursuant to section 10(d) of the Federal Advisory... clearly unwarranted invasion of personal privacy. Name of Committee: National Institute on Alcohol Abuse..., Scientific Review Officer, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health...

78 FR 63483 - National Institute on Alcohol Abuse and Alcoholism; Notice of Closed Meeting

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2013-10-24

... Alcohol Abuse and Alcoholism; Notice of Closed Meeting Pursuant to section 10(d) of the Federal Advisory... Alcohol Abuse and Alcoholism Special Emphasis Panel NIAAA Member Conflict Applications--Epidemiology and....273, Alcohol Research Programs; National Institutes of Health, HHS) Dated: October 18, 2013. Carolyn A...

75 FR 42451 - National Institute on Alcohol Abuse and Alcoholism; Notice of Closed Meeting

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2010-07-21

... Alcohol Abuse and Alcoholism; Notice of Closed Meeting Pursuant to section 10(d) of the Federal Advisory... and Alcoholism, Initial Review Group, Neuroscience Review Subcommittee. Date: November 2-3, 2010. Time..., Scientific Review Officer, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health...

Associations between alcohol outlet densities and adolescent alcohol consumption: a study in Australian students.

PubMed

Rowland, B; Toumbourou, J W; Satyen, L; Tooley, G; Hall, J; Livingston, M; Williams, J

2014-01-01

To assess whether the density of alcohol sales outlets in specific geographic communities is associated with adolescent alcohol consumption. A cross-sectional representative sample of secondary school students from Victoria, Australia (N=10,143), aged between 12 and 17 years, self-reported on alcohol use in the last 30 days in 2009. The density of alcohol outlets per local community area was merged with this information. After controlling for risk factors, multilevel modelling (MLM) revealed a statistical interaction between age and density on alcohol consumption. While older adolescents had higher alcohol consumption, increases in the density of alcohol outlets were only significantly associated with increased risk of alcohol consumption for adolescents between the ages of 12 and 14. Increased alcohol availability was associated with an increased risk of alcohol consumption specifically for early adolescents (12 and 14 years). Potential mechanisms as to how density is associated with direct and indirect alcohol availability, such as through parents or older siblings, need to be explored in future research. © 2013 Elsevier Ltd. All rights reserved.

HOW CAN WE USE OUR KNOWLEDGE OF ALCOHOL-TOBACCO INTERACTIONS TO REDUCE ALCOHOL USE?

PubMed Central

McKee, Sherry A.; Weinberger, Andrea H.

2013-01-01

Currently, 8.5% of the US population meets criteria for alcohol use disorders, with a total cost to the US economy estimated at $234 billion per year. Alcohol and tobacco use share a high degree of co-morbidity and interact across many levels of analysis. This review begins by highlighting alcohol and tobacco co-morbidity and presenting evidence that tobacco increases the risk for alcohol misuse and likely has a causal role in this relationship. We then discuss how knowledge of alcohol and tobacco interactions can be used to reduce alcohol use focusing on whether; 1) smoking status can be used as a clinical indicator for alcohol misuse; 2) tobacco policies reduce alcohol use; and 3) nAChR medications can be used to treat alcohol use disorders. PMID:23157448

Meta-Analysis of the Association of Alcohol-Related Social Media Use with Alcohol Consumption and Alcohol-Related Problems in Adolescents and Young Adults.

PubMed

Curtis, Brenda L; Lookatch, Samantha J; Ramo, Danielle E; McKay, James R; Feinn, Richard S; Kranzler, Henry R

2018-06-01

Despite the pervasive use of social media by young adults, there is comparatively little known about whether, and how, engagement in social media influences this group's drinking patterns and risk of alcohol-related problems. We examined the relations between young adults' alcohol-related social media engagement (defined as the posting, liking, commenting, and viewing of alcohol-related social media content) and their drinking behavior and problems. We conducted a systematic review and meta-analysis of studies evaluating the association of alcohol consumption and alcohol-related problems with alcohol-related social media engagement. Summary baseline variables regarding the social media platform used (e.g., Facebook and Twitter), social media measures assessed (e.g., number of alcohol photographs posted), alcohol measures (e.g., Alcohol Use Disorders Identification Test and Timeline Follow back Interview), and the number of time points at which data were collected were extracted from each published study. We used the Q statistic to examine heterogeneity in the correlations between alcohol-related social media engagement and both drinking behavior and alcohol-related problems. Because there was significant heterogeneity, we used a random-effects model to evaluate the difference from zero of the weighted aggregate correlations. We used metaregression with study characteristics as moderators to test for moderators of the observed heterogeneity. Following screening, 19 articles met inclusion criteria for the meta-analysis. The primary findings indicated a statistically significant relationship and moderate effect sizes between alcohol-related social media engagement and both alcohol consumption (r = 0.36, 95% CI: 0.29 to 0.44, p < 0.001) and alcohol-related problems (r = 0.37, 95% CI: 0.21 to 0.51, p < 0.001). There was significant heterogeneity among studies. Two significant predictors of heterogeneity were (i) whether there was joint measurement of alcohol

Alcohol consumption, masculinity, and alcohol-related violence and anti-social behaviour in sportspeople.

PubMed

O'Brien, Kerry S; Forrest, Walter; Greenlees, Iain; Rhind, Daniel; Jowett, Sophia; Pinsky, Ilana; Espelt, Albert; Bosque-Prous, Marina; Sonderlund, Anders Larrabee; Vergani, Matteo; Iqbal, Muhammad

2018-04-01

There is no research examining alcohol-related aggression and anti-social behaviour in UK or European sportspeople (athletes), and no research has examined relationships between masculinity, alcohol consumption, and alcohol-related aggression and antisocial behaviour in sportspeople (athletes). This study addresses this gap. Cross-sectional. A sample (N=2048; women=892, 44%) of in season sportspeople enrolled at UK universities (response 83%), completed measures of masculinity, alcohol consumption, within-sport (on-field) violence, and having been the perpetrator and/or victim of alcohol-related violent/aggressive and antisocial behaviour (e.g., hit/assaulted, vandalism, sexual assault). Logistic regressions examined predictors of alcohol-related violence/aggression and anti-social behaviours. Significant bivariate relationships between masculinity, within-sport violence, alcohol consumption, and alcohol-related aggression and anti-social behaviour were found for both men and women (p's<.001). Logistic regression adjusting for all variables showed that higher levels of masculinity and alcohol consumption in men and women were related to an increased odds of having conducted an aggressive, violent and/or anti-social act in the past 12 months when intoxicated. Odds ratios were largest for relationships between masculinity, alcohol consumption, within-sport violence, and interpersonal violence/aggression (p's<.001). A similar pattern of results was found for having been the victim of aggression and anti-social behaviour. Alcohol-related aggression and anti-social behaviour appear to be problematic in UK university sportspeople, and is related to masculinity and excessive drinking. Interventions that reduce excessive alcohol consumption, masculine norms and associated within-sport violence, could be effective in reducing alcohol-related aggression and antisocial behaviour in UK sportspeople. Copyright © 2017 Sports Medicine Australia. Published by Elsevier Ltd. All

Contribution of liver alcohol dehydrogenase to metabolism of alcohols in rats.

PubMed

Plapp, Bryce V; Leidal, Kevin G; Murch, Bruce P; Green, David W

2015-06-05

The kinetics of oxidation of various alcohols by purified rat liver alcohol dehydrogenase (ADH) were compared with the kinetics of elimination of the alcohols in rats in order to investigate the roles of ADH and other factors that contribute to the rates of metabolism of alcohols. Primary alcohols (ethanol, 1-propanol, 1-butanol, 2-methyl-1-propanol, 3-methyl-1-butanol) and diols (1,3-propanediol, 1,3-butanediol, 1,4-butanediol, 1,5-pentanediol) were eliminated in rats with zero-order kinetics at doses of 5-20 mmol/kg. Ethanol was eliminated most rapidly, at 7.9 mmol/kgh. Secondary alcohols (2-propanol-d7, 2-propanol, 2-butanol, 3-pentanol, cyclopentanol, cyclohexanol) were eliminated with first order kinetics at doses of 5-10 mmol/kg, and the corresponding ketones were formed and slowly eliminated with zero or first order kinetics. The rates of elimination of various alcohols were inhibited on average 73% (55% for 2-propanol to 90% for ethanol) by 1 mmol/kg of 4-methylpyrazole, a good inhibitor of ADH, indicating a major role for ADH in the metabolism of the alcohols. The Michaelis kinetic constants from in vitro studies (pH 7.3, 37 °C) with isolated rat liver enzyme were used to calculate the expected relative rates of metabolism in rats. The rates of elimination generally increased with increased activity of ADH, but a maximum rate of 6±1 mmol/kg h was observed for the best substrates, suggesting that ADH activity is not solely rate-limiting. Because secondary alcohols only require one NAD(+) for the conversion to ketones whereas primary alcohols require two equivalents of NAD(+) for oxidation to the carboxylic acids, it appears that the rate of oxidation of NADH to NAD(+) is not a major limiting factor for metabolism of these alcohols, but the rate-limiting factors are yet to be identified. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Contribution of Liver Alcohol Dehydrogenase to Metabolism of Alcohols in Rats

PubMed Central

Plapp, Bryce V.; Leidal, Kevin G.; Murch, Bruce P.; Green, David W.

2015-01-01

The kinetics of oxidation of various alcohols by purified rat liver alcohol dehydrogenase (ADH) were compared with the kinetics of elimination of the alcohols in rats in order to investigate the roles of ADH and other factors that contribute to the rates of metabolism of alcohols. Primary alcohols (ethanol, 1-propanol, 1-butanol, 2-methyl-1-propanol, 3-methyl-1-butanol) and diols (1,3-propanediol, 1,3-butanediol, 1,4-butanediol, 1,5-pentanediol) were eliminated in rats with zero-order kinetics at doses of 5–20 mmole/kg. Ethanol was eliminated most rapidly, at 7.9 mmole/kg•h. Secondary alcohols (2-propanol-d7, 2-propanol, 2-butanol, 3-pentanol, cyclopentanol, cyclohexanol) were eliminated with first order kinetics at doses of 5–10 mmole/kg, and the corresponding ketones were formed and slowly eliminated with zero or first order kinetics. The rates of elimination of various alcohols were inhibited on average 73% (55% for 2-propanol to 90% for ethanol) by 1 mmole/kg of 4-methylpyrazole, a good inhibitor of ADH, indicating a major role for ADH in the metabolism of the alcohols. The Michaelis kinetic constants from in vitro studies (pH 7.3, 37 °C) with isolated rat liver enzyme were used to calculate the expected relative rates of metabolism in rats. The rates of elimination generally increased with increased activity of ADH, but a maximum rate of 6 ± 1 mmole/kg•h was observed for the best substrates, suggesting that ADH activity is not solely rate-limiting. Because secondary alcohols only require one NAD+ for the conversion to ketones whereas primary alcohols require two equivalents of NAD+ for oxidation to the carboxylic acids, it appears that the rate of oxidation of NADH to NAD+ is not a major limiting factor for metabolism of these alcohols, but the rate-limiting factors are yet to be identified. PMID:25641189

78 FR 41938 - National Institute on Alcohol Abuse and Alcoholism; Notice of Closed Meeting

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2013-07-12

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78 FR 75929 - National Institute on Alcohol Abuse and Alcoholism; Notice of Closed Meeting

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2013-12-13

... Alcohol Abuse and Alcoholism; Notice of Closed Meeting Pursuant to section 10(d) of the Federal Advisory... clearly unwarranted invasion of personal privacy. Name of Committee: National Institute on Alcohol Abuse... Alcohol Abuse and Alcoholism, 5635 Fishers Lane, T508, Rockville, MD 20852. Contact Person: Beata Buzas...

76 FR 44597 - National Institute on Alcohol Abuse and Alcoholism; Notice of Closed Meeting

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2011-07-26

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76 FR 44596 - National Institute on Alcohol Abuse and Alcoholism; Notice of Closed Meeting

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2011-07-26

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75 FR 42756 - National Institute on Alcohol Abuse and Alcoholism; Notice of Closed Meeting

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2010-07-22

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75 FR 24961 - National Institute on Alcohol Abuse and Alcoholism; Notice of Closed Meetings

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2010-05-06

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77 FR 70171 - National Institute on Alcohol Abuse and Alcoholism; Notice of Closed Meeting

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2012-11-23

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76 FR 44600 - National Institute on Alcohol Abuse and Alcoholism; Notice of Closed Meeting

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2011-07-26

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75 FR 69090 - National Institute on Alcohol Abuse and Alcoholism; Notice of Closed Meeting

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2010-11-10

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75 FR 57473 - National Institute on Alcohol Abuse and Alcoholism; Notice of Closed Meeting

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2010-09-21

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75 FR 53320 - National Institute on Alcohol Abuse and Alcoholism; Notice of Closed Meeting

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2010-08-31

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75 FR 42451 - National Institute on Alcohol Abuse and Alcoholism; Notice of Closed Meeting

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2010-07-21

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2011-09-27

... Alcohol Abuse and Alcoholism; Notice of Closed Meeting Pursuant to section 10(d) of the Federal Advisory... and Alcoholism Special Emphasis Panel, NIAAA Member Conflict Application Review. Date: October 26...: Richard A Rippe, PhD, Scientific Review Officer, National Institute on Alcohol Abuse and Alcoholism, 5635...

Animal models of alcoholism: neurobiology of high alcohol-drinking behavior in rodents.

PubMed

McBride, W J; Li, T K

1998-01-01

This review discusses efforts to develop rodent models for the study of neurobiological mechanisms underlying chronic alcohol drinking, alcoholism, and abnormal alcohol-seeking behavior. Selective breeding has produced stable lines of rats that reliably exhibit high and (for comparison purposes) low voluntary alcohol consumption. In addition, animal models of chronic ethanol self-administration have been developed in rodents, who do not have a genetic predisposition for high alcohol-seeking behavior, to explore environmental influences in ethanol drinking and the effects of physical dependence on alcohol self-administration. The selectively bred high-preference animals reliably self-administer ethanol by free-choice drinking and operantly respond for oral ethanol in amounts that produce pharmacologically meaningful blood alcohol concentrations (50 to 200 mg% and higher). In addition, the alcohol-preferring rats will self-administer ethanol by intragastric infusion. With chronic free-choice drinking, the high alcohol-preferring rats develop tolerance to the high-dose effects of ethanol and show signs of physical dependence after the withdrawal of alcohol. Compared with nonpreferring animals, the alcohol-preferring rats are less sensitive to the sedative-hypnotic effects of ethanol and develop tolerance more quickly to high-dose ethanol. Nonselected common stock rats can be trained to chronically self-administer ethanol following its initial presentation in a palatable sucrose or saccharin solution, and the gradual replacement of the sucrose or saccharin with ethanol (the sucrose/saccharin-fade technique). Moreover, rats that are trained in this manner and then made dependent by ethanol-vapor inhalation or liquid diet increase their ethanol self-administration during the withdrawal period. Both the selectively bred rats and common-stock rats demonstrate "relapse" and an alcohol deprivation effect following 2 or more weeks of abstinence. Systemic administration of

Towards a global alcohol policy: alcohol, public health and the role of WHO.

PubMed Central

Jernigan, D. H.; Monteiro, M.; Room, R.; Saxena, S.

2000-01-01

In 1983 the World Health Assembly declared alcohol-related problems to be among the world's major health concerns. Since then, alcohol consumption has risen in developing countries, where it takes a heavy toll. Alcohol-related problems are at epidemic levels in the successor states of the Soviet Union and are responsible for 3.5% of disability-adjusted life years (DALYs) lost globally. Substantial evidence exists of the relationship between the levels and patterns of alcohol consumption on the one hand and the incidence of alcohol-related problems on the other. Over the past 20 years, research has demonstrated the effectiveness of public policies involving, for example, taxation and restrictions on alcohol availability, in reducing alcohol-related problems. In the wake of rapid economic globalization, many of these policies at national and subnational levels have been eroded, often with the support of international financial and development organizations. Development agencies and international trade agreements have treated alcohol as a normal commodity, overlooking the adverse consequences of its consumption on productivity and health. WHO is in a strong position to take the lead in developing a global alcohol policy aimed at reducing alcohol-related problems, providing scientific and statistical support, capacity-building, disseminating effective strategies and collaborating with other international organizations. Such leadership can play a significant part in diminishing the health and social problems associated with alcohol use. PMID:10885168

Consumption of alcohol and risk of alcohol addiction among students in Poland.

PubMed

Wilczyński, Krzysztof; Witowski, Łukasz; Pawlik, Aleksandra; Krysta, Krzysztof; Krupka-Matuszczyk, Irena

2013-09-01

Alcohol consumption in our society is a known, and a widely discussed problem, due to the proven negative impact of excessive usage of spirits on health. Aim of the study was to evaluate the rate of consumption, and risk of an alcoholic disease among Polish students. Study was carried out using an authors' own questionnaire, made of a queries about amount and frequency of alcohol consumption, risky behaviors and knowledge about alcoholism. Research was conducted through community portals (f.e. facebook.com), and within 3 weeks time (from a 10(th) of January to 31(st) of January 2013) 1300 students from different Polish universities participated in it. Out of them, after removal of inadequate questionnaires, group of 1259 students (822 females, 437 males) was selected for further analysis. Average age equaled to 21.5, with the maximum of 27 and minimum of 18 years. For the statistical analysis StatSoft "Statistica" 10.0 software was used. The study shows that 95.5% of students use alcohol (mostly beer and vodka) and they tend to overuse it. 28.86% of respondents drank excessively more than 3 times during the month preceding research, 46% of subjects also had an alcoholic palimpsest more than once, 12.7% need an alcohol to enjoy a party and 0.83% of respondents can't control the amount of a one-time alcohol consumption. 3.32% of students may be in the group of a high alcoholism risk. Alcohol consumption is a common problem among Polish students. Most of respondents, mostly males, drink excessively and potentially risky for their health. There is a remarkable group of students endangered with alcohol addiction.

The International Alcohol Control (IAC) study-evaluating the impact of alcohol policies.

PubMed

Casswell, Sally; Meier, Petra; MacKintosh, Anne M; Brown, Abraham; Hastings, Gerard; Thamarangsi, Thaksaphon; Chaiyasong, Surasak; Chun, Sungsoo; Huckle, Taisia; Wall, Martin; You, Ru Q

2012-08-01

This paper describes a new multicountry collaborative project to assess the impact of alcohol control policy. Longitudinal surveys of drinkers in a number of participating countries and analysis of the policy context allow for the assessment of change over time within countries and comparison between countries. The design of the study is modeled on the International Tobacco Control study and aims to assess the impact of alcohol policies in different cultural contexts on policy-related behaviors and alcohol consumption. A survey instrument and protocol for policy analysis have been developed by the initial participating countries: England, Scotland, Thailand, South Korea, and New Zealand. The first round of data collection is scheduled for 2011-2012. The survey instrument (International Alcohol Control [IAC] survey) measures key policy relevant behaviors: place and time of purchase, amounts purchased and price paid; ease of access to alcohol purchase; alcohol marketing measures; social supply; perceptions of alcohol affordability and availability and salience of price; perceptions of enforcement; people's experiences with specific alcohol restrictions; support for policy and consumption (typical quantity, frequency using beverage and location-specific measures). The Policy Analysis Protocol (PoLAP) assesses relevant aspects of the policy environment including regulation and implementation. It has proved feasible to design instruments to collect detailed data on behaviors relevant to alcohol policy change and to assess the policy environment in different cultural settings. In a policy arena in which the interest groups and stakeholders have different perceptions of appropriate policy responses to alcohol-related harm, a robust methodology to assess the impact of policy will contribute to the debate. Copyright © 2012 by the Research Society on Alcoholism.

Effect of Maryland's 2011 Alcohol Sales Tax Increase on Alcohol-Positive Driving.

PubMed

Lavoie, Marie-Claude; Langenberg, Patricia; Villaveces, Andres; Dischinger, Patricia C; Simoni-Wastila, Linda; Hoke, Kathleen; Smith, Gordon S

2017-07-01

The 2011 Maryland alcohol sales tax increase from 6% to 9% provided an opportunity to evaluate the impact on rates of alcohol-positive drivers involved in injury crashes. Maryland police crash reports from 2001 to 2013 were analyzed using an interrupted time series design and a multivariable analysis employing generalized estimating equations models with a negative binomial distribution. Data were analyzed in 2014-2015. There was a significant gradual annual reduction of 6% in the population-based rate of all alcohol-positive drivers (p<0.03), and a 12% reduction for drivers aged 15-20 years (p<0.007), and 21-34 years (p<0.001) following the alcohol sales tax increase. There were no significant changes in rates of alcohol-positive drivers aged 35-54 years (rate ratio, 0.98; 95% CI=0.89, 1.09). Drivers aged ≥55 years had a significant immediate 10% increase in the rate of alcohol-positive drivers (rate ratio, 1.10; 95% CI=1.04, 1.16) and a gradual increase of 4.8% per year after the intervention. Models using different denominators and controlling for multiple factors including a proxy for unmeasured factors found similar results overall. The 2011 Maryland alcohol sales tax increase led to a significant reduction in the rate of all alcohol-positive drivers involved in injury crashes especially among drivers aged 15-34 years. This is the first study to examine the impact of alcohol sales taxes on crashes; previous research focused on excise tax. Increasing alcohol taxes is an important but often neglected intervention to reduce alcohol-impaired driving. Copyright © 2017 American Journal of Preventive Medicine. Published by Elsevier Inc. All rights reserved.

27 CFR 19.366 - Alcohol.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 27 Alcohol, Tobacco Products and Firearms 1 2011-04-01 2011-04-01 false Alcohol. 19.366 Section 19.366 Alcohol, Tobacco Products and Firearms ALCOHOL AND TOBACCO TAX AND TRADE BUREAU, DEPARTMENT OF THE..., and Removal of Products § 19.366 Alcohol. (a) Containers. A proprietor may put alcohol for industrial...

Reducing the standard serving size of alcoholic beverages prompts reductions in alcohol consumption.

PubMed

Kersbergen, Inge; Oldham, Melissa; Jones, Andrew; Field, Matt; Angus, Colin; Robinson, Eric

2018-05-14

To test whether reducing the standard serving size of alcoholic beverages would reduce voluntary alcohol consumption in a laboratory (study 1) and a real-world drinking environment (study 2). Additionally, we modelled the potential public health benefit of reducing the standard serving size of on-trade alcoholic beverages in the United Kingdom. Studies 1 and 2 were cluster-randomized experiments. In the additional study, we used the Sheffield Alcohol Policy Model to estimate the number of deaths and hospital admissions that would be averted per year in the United Kingdom if a policy that reduces alcohol serving sizes in the on-trade was introduced. A semi-naturalistic laboratory (study 1), a bar in Liverpool, UK (study 2). Students and university staff members (study 1: n = 114, mean age = 24.8 years, 74.6% female), residents from local community (study 2: n = 164, mean age = 34.9 years, 57.3% female). In study 1, participants were assigned randomly to receive standard or reduced serving sizes (by 25%) of alcohol during a laboratory drinking session. In study 2, customers at a bar were served alcohol in either standard or reduced serving sizes (by 28.6-33.3%). Outcome measures were units of alcohol consumed within 1 hour (study 1) and up to 3 hours (study 2). Serving size condition was the primary predictor. In study 1, a 25% reduction in alcohol serving size led to a 20.7-22.3% reduction in alcohol consumption. In study 2, a 28.6-33.3% reduction in alcohol serving size led to a 32.4-39.6% reduction in alcohol consumption. Modelling results indicated that decreasing the serving size of on-trade alcoholic beverages by 25% could reduce the number of alcohol-related hospital admissions and deaths per year in the United Kingdom by 4.4-10.5% and 5.6-13.2%, respectively. Reducing the serving size of alcoholic beverages in the United Kingdom appears to lead to a reduction in alcohol consumption within a single drinking occasion. © 2018 The Authors. Addiction

How alcohol industry organisations mislead the public about alcohol and cancer.

PubMed

Petticrew, Mark; Maani Hessari, Nason; Knai, Cécile; Weiderpass, Elisabete

2018-03-01

Alcohol consumption increases the risk of several types of cancer, including several common cancers. As part of their corporate social responsibility activities, the alcohol industry (AI) disseminates information about alcohol and cancer. We examined the information on this which the AI disseminates to the public through its 'social aspects and public relations organizations' and related bodies. The aim of the study was to determine its comprehensiveness and accuracy. Qualitative analysis of websites and documents from 27 AI organisations. All text relating to cancer was extracted and analysed thematically. Most of the organisations were found to disseminate misrepresentations of the evidence about the association between alcohol and cancer. Three main industry strategies were identified: (i) denial/omission: denying, omitting or disputing the evidence that alcohol consumption increases cancer risk; (ii) distortion: mentioning cancer, but misrepresenting the risk; and (iii) distraction: focussing discussion away from the independent effects of alcohol on common cancers. Breast cancer and colorectal cancer appeared to be a particular focus for this misrepresentation. The AI appears to be engaged in the extensive misrepresentation of evidence about the alcohol-related risk of cancer. These activities have parallels with those of the tobacco industry. This finding is important because the industry is involved in developing alcohol policy in many countries, and in disseminating health information to the public, including schoolchildren. Policymakers, academics, public health and other practitioners should reconsider the appropriateness of their relationships to these AI bodies. © 2017 Australasian Professional Society on Alcohol and other Drugs.

Neurologic complications of alcoholism.

PubMed

Noble, James M; Weimer, Louis H

2014-06-01

This review serves as an overview of neurologic conditions associated with alcohol abuse or withdrawal, including epidemiology, clinical symptoms, diagnostic approach, and treatment. Frequent alcohol abuse and frank alcoholism are very common among adults in the United States. Although rates decline with each decade, as many as 10% of the elderly drink excessively. Given the ubiquitous nature of alcoholism in society, its complications have been clinically recognized for generations, with recent advances focusing on improved understanding of ethanol's biochemical targets and the pathophysiology of its complications. The chronic effects of alcohol abuse are myriad and include neurologic complications through both direct and indirect effects on the central and peripheral nervous systems. These disorders include several encephalopathic states related to alcohol intoxication, withdrawal, and related nutritional deficiencies; acute and chronic toxic and nutritional peripheral neuropathies; and myopathy. Although prevention of alcoholism and its neurologic complications is the optimal strategy, this article reviews the specific treatment algorithms for alcohol withdrawal and its related nutritional deficiency states.