Genomes and Genes
diacylglycerol o acyltransferase
Summary: An enzyme that catalyses the last step of the TRIACYLGLYCEROL synthesis reaction in which diacylglycerol is covalently joined to LONG-CHAIN ACYL COA to form triglyceride. It was formerly categorized as EC 188.8.131.52.
- Herault F, Saez G, Robert E, Al Mohammad A, Davail S, Chartrin P, et al. Liver gene expression in relation to hepatic steatosis and lipid secretion in two duck species. Anim Genet. 2010;41:12-20 pubmed publisher..These results should shed light on gene expression that might underlie susceptibility to hepatic steatosis in humans. ..
- Liu L, Shi X, Bharadwaj K, Ikeda S, Yamashita H, Yagyu H, et al. DGAT1 expression increases heart triglyceride content but ameliorates lipotoxicity. J Biol Chem. 2009;284:36312-23 pubmed publisher..Moreover, induction of DGAT1 could be beneficial in the setting of excess heart accumulation of toxic lipids. ..
- Siloto R, Truksa M, He X, McKeon T, Weselake R. Simple methods to detect triacylglycerol biosynthesis in a yeast-based recombinant system. Lipids. 2009;44:963-73 pubmed publisher..The methods can be used for a variety of applications such as isolation of novel genes, directed evolution, gene-specific drug screening and will facilitate novel approaches in the research of TAG-SE. ..
- Wongsiriroj N, Piantedosi R, Palczewski K, Goldberg I, Johnston T, Li E, et al. The molecular basis of retinoid absorption: a genetic dissection. J Biol Chem. 2008;283:13510-9 pubmed publisher..Contrary to what has been proposed in the literature based on in vitro studies, CRBPII does not directly prevent retinol from being acted upon by DGAT1 or other intestinal ARATs in vivo. ..
- Herker E, Harris C, Hernandez C, Carpentier A, Kaehlcke K, Rosenberg A, et al. Efficient hepatitis C virus particle formation requires diacylglycerol acyltransferase-1. Nat Med. 2010;16:1295-8 pubmed publisher..Inhibition of DGAT1 activity or RNAi-mediated knockdown of DGAT1 severely impairs infectious virion production, implicating DGAT1 as a new target for antiviral therapy. ..
- Shi Y, Cheng D. Beyond triglyceride synthesis: the dynamic functional roles of MGAT and DGAT enzymes in energy metabolism. Am J Physiol Endocrinol Metab. 2009;297:E10-8 pubmed publisher..Consequently, selective inhibition of MGAT or DGAT enzymes by synthetic compounds may provide novel treatment for obesity and its related metabolic complications. ..
- Yang K, Noh J, Kim Y, Gang G, Hwang J, Yang S, et al. Differential modulatory effects of rosiglitazone and pioglitazone on white adipose tissue in db/db mice. Life Sci. 2010;87:405-10 pubmed publisher..these results suggest that pioglitazone activates lipid deposition by increasing lipid synthesis and transport, but rosiglitazone stimulates ?-oxidation and energy expenditure in adipocytes of db/db mice. ..
- Sirakova T, Dubey V, Deb C, Daniel J, Korotkova T, Abomoelak B, et al. Identification of a diacylglycerol acyltransferase gene involved in accumulation of triacylglycerol in Mycobacterium tuberculosis under stress. Microbiology. 2006;152:2717-25 pubmed..If TG storage is needed for the long-term survival of M. tuberculosis under dormant conditions, the tgs1 product could be a suitable target for antilatency drugs. ..
- Barbosa da Silva M, Sonstegard T, Thallman R, Connor E, Schnabel R, Van Tassell C. Characterization of DGAT1 allelic effects in a sample of North American Holstein cattle. Anim Biotechnol. 2010;21:88-99 pubmed publisher..Because of the strong antagonism between fat and protein yield and how those traits influence economic indices, selection for DGAT1 genotypes will likely not find widespread application in the U.S. ..
- Skinner J, Shew T, Schwartz D, Tzekov A, Lepus C, Abumrad N, et al. Diacylglycerol enrichment of endoplasmic reticulum or lipid droplets recruits perilipin 3/TIP47 during lipid storage and mobilization. J Biol Chem. 2009;284:30941-8 pubmed publisher..Membrane-permeable DG also drove perilipin 4 and 5 onto the ER. Together the data suggest that these lipid droplet proteins are recruited to DG-enriched membranes thereby linking lipid coat proteins to the metabolic state of the cell. ..
- Garbarino J, Padamsee M, Wilcox L, Oelkers P, D Ambrosio D, Ruggles K, et al. Sterol and diacylglycerol acyltransferase deficiency triggers fatty acid-mediated cell death. J Biol Chem. 2009;284:30994-1005 pubmed publisher..In metazoans, many of these processes are implicated in insulin secretion thus linking lipotoxicity with early aspects of pancreatic beta-cell dysfunction, diabetes, and the metabolic syndrome. ..
- Talhari D, Moraes M, Castilho P, Oliveira O, Beltramini L, Araujo A. Interaction of a C-terminal peptide of Bos taurus diacylglycerol acyltransferase 1 with model membranes. Biochim Biophys Acta. 2009;1788:2320-5 pubmed publisher..Our results therefore provide molecular-level evidence for the interaction between this domain and the substrates OCoA and DOG for the synthesis of triacylglycerol. ..
- Heier C, Taschler U, Rengachari S, Oberer M, Wolinski H, Natter K, et al. Identification of Yju3p as functional orthologue of mammalian monoglyceride lipase in the yeast Saccharomycescerevisiae. Biochim Biophys Acta. 2010;1801:1063-71 pubmed publisher..In conclusion, our studies suggest that catabolic and anabolic reactions affect cellular MAG levels. Yju3p is the functional orthologue of mammalian MGL and is required for efficient degradation of MAG in yeast. ..
- Nakada Y, Aicher T, Le Huerou Y, Turner T, Pratt S, Gonzales S, et al. Novel acyl coenzyme A (CoA): diacylglycerol acyltransferase-1 inhibitors: synthesis and biological activities of diacylethylenediamine derivatives. Bioorg Med Chem. 2010;18:2785-95 pubmed publisher..Oral administration of 3x to mice with dietary-induced obesity resulted in reduced body weight gain and white adipose tissue weight. ..
- Lee B, Fast A, Zhu J, Cheng J, Buhman K. Intestine-specific expression of acyl CoA:diacylglycerol acyltransferase 1 reverses resistance to diet-induced hepatic steatosis and obesity in Dgat1-/- mice. J Lipid Res. 2010;51:1770-80 pubmed publisher..The results presented demonstrate that intestinal DGAT1 stimulates dietary fat secretion out of enterocytes and that altering this cellular function alters the fate of dietary fat in specific tissues. ..
- Sun F, Xie M, Xue J, Wang H. Osthol regulates hepatic PPAR alpha-mediated lipogenic gene expression in alcoholic fatty liver murine. Phytomedicine. 2010;17:669-73 pubmed publisher..It was concluded that osthol might regulate the gene expressions of DGAT, HMG-CoA reductase and CYP7A via increasing the PPAR alpha mRNA expression. ..
- Quintero M, Cabañas M, Arus C. 13C-labelling studies indicate compartmentalized synthesis of triacylglycerols in C6 rat glioma cells. Biochim Biophys Acta. 2010;1801:693-701 pubmed publisher..The results we have obtained with C6 cells may also apply to other cellular systems and should be taken into account when interpreting ML dynamics detected by NMR in vivo. ..
- Soumura M, Kume S, Isshiki K, Takeda N, Araki S, Tanaka Y, et al. Oleate and eicosapentaenoic acid attenuate palmitate-induced inflammation and apoptosis in renal proximal tubular cell. Biochem Biophys Res Commun. 2010;402:265-71 pubmed publisher..These results suggest that oleate and EPA have protective effects against the palmitate-induced renal tubular cell damage by inhibiting PKC? activation...
- Martinez Royo A, Ordovas L, Zaragoza P, Altarriba J, Serrano M, Rodellar C, et al. The bovine annexin 9 gene (ANXA9) is significantly associated with milk-fat yield in a Spanish Holstein-Friesian population. Res Vet Sci. 2010;88:452-5 pubmed publisher..Our results suggest that the ANXA9 gene polymorphism or a linked segregating QTL contributes to variation in milk-fat yield. ..
- Kimura K, Tomita N, Uemura H, Aki T, Ono K, Kamisaka Y. Improvement of Stearidonic acid production in Oleaginous Saccharomyces cerevisiae. Biosci Biotechnol Biochem. 2009;73:1447-9 pubmed..7 g/l alpha-linolenic acid for 7 d, 0.4 g of alpha-linolenic acid was accumulated and 44 mg of stearidonic acid was produced, mainly as a triacylglycerol in the 1 liter broth. ..
- Rosenblat M, Coleman R, Reddy S, Aviram M. Paraoxonase 2 attenuates macrophage triglyceride accumulation via inhibition of diacylglycerol acyltransferase 1. J Lipid Res. 2009;50:870-9 pubmed publisher..We thus conclude that PON2 attenuates macrophage triglyceride accumulation and foam cell formation via inhibition of microsomal DGAT1 activity, which appears to be sensitive to oxidative state. ..
- Rani S, Krishna T, Saha S, Negi A, Rajasekharan R. Defective in cuticular ridges (DCR) of Arabidopsis thaliana, a gene associated with surface cutin formation, encodes a soluble diacylglycerol acyltransferase. J Biol Chem. 2010;285:38337-47 pubmed publisher..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. ..
- Demeter R, Schopen G, Lansink A, Meuwissen M, van Arendonk J. Effects of milk fat composition, DGAT1, and SCD1 on fertility traits in Dutch Holstein cattle. J Dairy Sci. 2009;92:5720-9 pubmed publisher..Our results can be used to assess the correlated effects of breeding for improved milk fat composition on reproduction, thereby allowing for better evaluation of breeding programs before implementation. ..
- Banke N, Wende A, Leone T, O Donnell J, Abel E, Kelly D, et al. Preferential oxidation of triacylglyceride-derived fatty acids in heart is augmented by the nuclear receptor PPARalpha. Circ Res. 2010;107:233-41 pubmed publisher..Accelerated palmitoyl turnover in TAG, attributable to chronic PPARalpha activation, results in near requisite oxidation of LCFAs from TAG. ..
- Watson E, Fargali S, Okamoto H, Sadahiro M, Gordon R, Chakraborty T, et al. Analysis of knockout mice suggests a role for VGF in the control of fat storage and energy expenditure. BMC Physiol. 2009;9:19 pubmed publisher..Lastly, despite being hypermetabolic, VGF knockout mice were cold intolerant. We propose that VGF and/or VGF-derived peptides modulate sympathetic outflow pathways to regulate fat storage and energy expenditure. ..
- Conte G, Mele M, Chessa S, Castiglioni B, Serra A, Pagnacco G, et al. Diacylglycerol acyltransferase 1, stearoyl-CoA desaturase 1, and sterol regulatory element binding protein 1 gene polymorphisms and milk fatty acid composition in Italian Brown cattle. J Dairy Sci. 2010;93:753-63 pubmed publisher..However, the unbalanced distribution of alleles in all polymorphisms investigated suggested that the size of population should be increased to confirm the results of the present study. ..
- Yamamoto T, Yamaguchi H, Miki H, Shimada M, Nakada Y, Ogino M, et al. Coenzyme A: diacylglycerol acyltransferase 1 inhibitor ameliorates obesity, liver steatosis, and lipid metabolism abnormality in KKAy mice fed high-fat or high-carbohydrate diets. Eur J Pharmacol. 2010;640:243-9 pubmed publisher..These results suggest that Compound-Z is a promising and attractive agent not only for the treatment of obesity but also hepatic steatosis and circulating lipid abnormalities that are the leading causes of atherosclerosis. ..
- Choi J, Choi J, Lee S, Lee S, Kim K, Kim Y. Inhibitory activity of diacylglycerol acyltransferase by glabrol isolated from the roots of licorice. Arch Pharm Res. 2010;33:237-42 pubmed publisher..These data suggest that potential therapy for the treatment in obesity and type 2 diabetes patients by licorice roots might be related with its DGAT inhibitory effect. ..
- MaÃ±as FernÃ¡ndez A, Vilches FerrÃ³n M, Garrido CÃ¡rdenas J, Belarbi E, Alonso D, GarcÃa Maroto F. Cloning and molecular characterization of the acyl-CoA: diacylglycerol acyltransferase 1 (DGAT1) gene from Echium. Lipids. 2009;44:555-68 pubmed publisher..Transcript analysis for EpDGAT shows an ubiquitous expression of the gene which is increased in leaves during senescence. ..
- Villanueva C, Monetti M, Shih M, Zhou P, Watkins S, Bhanot S, et al. Specific role for acyl CoA:Diacylglycerol acyltransferase 1 (Dgat1) in hepatic steatosis due to exogenous fatty acids. Hepatology. 2009;50:434-42 pubmed publisher..Our findings identify a specific role for hepatic DGAT1 in esterification of exogenous fatty acids and indicate that DGAT1 contributes to hepatic steatosis induced by this mechanism. ..
- Takahashi N, Li F, Hua K, Deng J, Wang C, Bowers R, et al. Increased energy expenditure, dietary fat wasting, and resistance to diet-induced obesity in mice lacking renin. Cell Metab. 2007;6:506-12 pubmed..Most of the metabolic changes in Ren1c(-/-) mice were reversed by angiotensin II administration. These results support a role for angiotensin II in the pathogenesis of diet-induced obesity and insulin resistance. ..
- Srivastava R. Fenofibrate ameliorates diabetic and dyslipidemic profiles in KKAy mice partly via down-regulation of 11beta-HSD1, PEPCK and DGAT2. Comparison of PPARalpha, PPARgamma, and liver x receptor agonists. Eur J Pharmacol. 2009;607:258-63 pubmed publisher..It is also shown that the undesirable lipogenic effects of T090317 could be dampened by fenofibrate. ..
- Bong J, Cho K, Baik M. Comparison of gene expression profiling between bovine subcutaneous and intramuscular adipose tissues by serial analysis of gene expression. Cell Biol Int. 2009;34:125-33 pubmed publisher..Our SAGE experiment provides a differential gene expression profile in subcutaneous and intramuscular adipose tissues of Korean cattle. This information will be useful in developing method(s) to produce high-marble beef. ..
- Liu L, Shi X, Choi C, Shulman G, Klaus K, Nair K, et al. Paradoxical coupling of triglyceride synthesis and fatty acid oxidation in skeletal muscle overexpressing DGAT1. Diabetes. 2009;58:2516-24 pubmed publisher..Seemingly paradoxical, this phenomenon is characteristic of insulin-sensitive myofibers and suggests that DGAT1 plays an active role in metabolic "remodeling" of skeletal muscle coupled with insulin sensitization. ..
- Andrianov V, Borisjuk N, Pogrebnyak N, Brinker A, Dixon J, Spitsin S, et al. Tobacco as a production platform for biofuel: overexpression of Arabidopsis DGAT and LEC2 genes increases accumulation and shifts the composition of lipids in green biomass. Plant Biotechnol J. 2010;8:277-87 pubmed publisher..8% per dry weight of total extracted FA. The obtained data reveal the potential of metabolically modified plant biomass for the production of biofuel. ..
- Li R, Yu K, Hatanaka T, Hildebrand D. Vernonia DGATs increase accumulation of epoxy fatty acids in oil. Plant Biotechnol J. 2010;8:184-95 pubmed publisher..Both DGAT1 and DGAT2 increase epoxy fatty acid accumulation with DGAT2 having much greater impact...
- Schennink A, Stoop W, Visker M, van Der Poel J, Bovenhuis H, van Arendonk J. Short communication: Genome-wide scan for bovine milk-fat composition. II. Quantitative trait loci for long-chain fatty acids. J Dairy Sci. 2009;92:4676-82 pubmed publisher..Suggestive QTL were found on 16 other chromosomes. The diacylglycerol acyltransferase 1 (DGAT1) K232A polymorphism on BTA14, which is known to influence fatty acid composition, most likely explains the QTL that was detected on BTA14. ..
- Krapivner S, Iglesias M, Silveira A, Tegner J, Björkegren J, Hamsten A, et al. DGAT1 participates in the effect of HNF4A on hepatic secretion of triglyceride-rich lipoproteins. Arterioscler Thromb Vasc Biol. 2010;30:962-7 pubmed publisher..50, P<0.0001) and between DGAT1 mRNA levels and plasma triglyceride concentration (r(2)=0.09, P<0.01). This study identified DGAT1 as an important protein that participates in the effect of HNF4A on hepatic secretion of TRLs. ..
- Siloto R, Truksa M, Brownfield D, Good A, Weselake R. Directed evolution of acyl-CoA:diacylglycerol acyltransferase: development and characterization of Brassica napus DGAT1 mutagenized libraries. Plant Physiol Biochem. 2009;47:456-61 pubmed publisher..The directed evolution approach could lead to the development of an improved plant DGAT1 for increasing seed oil content in oleaginous crops. ..
- Matsuda D, Tomoda H. Triazolo compounds useful as diacylglycerol acyltransferase1 inhibitor - WO2009126624. Expert Opin Ther Pat. 2010;20:1097-102 pubmed publisher..Among them, four derivatives inhibited DGAT activity with IC(50) values of < 0.1 microM. ..
- Souza F, Mercadante M, Fonseca L, Ferreira L, Regatieri I, Ayres D, et al. Assessment of DGAT1 and LEP gene polymorphisms in three Nelore (Bos indicus) lines selected for growth and their relationship with growth and carcass traits. J Anim Sci. 2010;88:435-41 pubmed publisher..However, more studies, with larger data sets, are necessary before these makers can be used for marker-assisted selection. ..
- McFie P, Stone S, Banman S, Stone S. Topological orientation of acyl-CoA:diacylglycerol acyltransferase-1 (DGAT1) and identification of a putative active site histidine and the role of the n terminus in dimer/tetramer formation. J Biol Chem. 2010;285:37377-87 pubmed publisher..Finally, we show that the N-terminal domain of DGAT1 is not required for the catalytic activity of DGAT1 but, instead, may be involved in regulating enzyme activity and dimer/tetramer formation. ..
- Hou X, Moser S, Sarr M, Thompson G, Que F, Jensen M. Visceral and subcutaneous adipose tissue diacylglycerol acyltransferase activity in humans. Obesity (Silver Spring). 2009;17:1129-34 pubmed publisher..Our results are consistent with the hypothesis that interindividual variations in DGAT activity may be an important regulatory step in visceral adipose tissue FFA uptake/storage. ..
- Sun D, Jia J, Ma Y, Wang Y, Yu Y, Zhang Y. Effects of DGAT1 and GHR on milk yield and milk composition in the Chinese dairy population. Anim Genet. 2009;40:997-1000 pubmed publisher..279Phe by p.279Tyr may lead to a significant increase in protein percentage. Our findings indicate that DGAT1 p.232Ala and GHR p.279Phe could be used to increase milk yield and protein yield of Chinese Holstein cows. ..
- Zhang J, Roddy T, Ho P, Horvath C, Vickers C, Stout S, et al. Assay development and screening of human DGAT1 inhibitors with an LC/MS-based assay: application of mass spectrometry for large-scale primary screening. J Biomol Screen. 2010;15:695-702 pubmed publisher..Results indicated that, through these innovative approaches, the LC/MS-based screening method is both feasible and suitable for high-throughput primary screening. ..
- Pannier L, Mullen A, Hamill R, Stapleton P, Sweeney T. Association analysis of single nucleotide polymorphisms in DGAT1, TG and FABP4 genes and intramuscular fat in crossbred Bos taurus cattle. Meat Sci. 2010;85:515-8 pubmed publisher..The results confirm the lack of an association found by many other studies and suggest that these SNPs are not influential on the divergent IMF levels in the crossbred population tested. ..
- Festuccia W, Blanchard P, Richard D, Deshaies Y. Basal adrenergic tone is required for maximal stimulation of rat brown adipose tissue UCP1 expression by chronic PPAR-gamma activation. Am J Physiol Regul Integr Comp Physiol. 2010;299:R159-67 pubmed publisher..The residual sympathetic tone found under rosiglitazone treatment is, therefore, involved in the modulation of a subset of major components of PPAR-gamma-mediated BAT recruitment. ..
- King A, Segreti J, Larson K, Souers A, Kym P, Reilly R, et al. In vivo efficacy of acyl CoA: diacylglycerol acyltransferase (DGAT) 1 inhibition in rodent models of postprandial hyperlipidemia. Eur J Pharmacol. 2010;637:155-61 pubmed publisher..Therefore, by attenuating postprandial hyperlipidemia, DGAT-1 inhibition may represent a novel therapeutic approach to reduce cardiovascular risk. ..
- Liu Q, Siloto R, Weselake R. Role of cysteine residues in thiol modification of acyl-CoA:diacylglycerol acyltransferase 2 from yeast. Biochemistry. 2010;49:3237-45 pubmed publisher..Our work indicates that although this cysteine does not play a role in enzymatic catalysis, it may reside in a crucial position that is near a possible active site of DGAT2 or related to proper folding of the protein. ..