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https://www.readbyqxmd.com/read/28739155/discovery-of-a-low-systemic-exposure-dgat-1-inhibitor-with-a-picolinoylpyrrolidine-2-carboxylic-acid-moiety
#1
Jianwei Yan, Gaihong Wang, Xiangyu Dang, Binbin Guo, Wuhong Chen, Ting Wang, Limin Zeng, Heyao Wang, Youhong Hu
A series of diacylglycerol O-acyltransferase 1 (DGAT-1) inhibitors with a picolinoylpyrrolidine-2-carboxylic acid moiety were designed and synthesized. Of these compounds, compound 22 exhibited excellent DGAT-1-inhibitory activity (hDGAT-1 enzyme assay, 50% inhibitory concentration [IC50]=3.5±0.9nM) and effectively reduced the intracellular triglyceride contents in 3T3-L1, HepG2 and Caco-2 cells. A preliminary study of the plasma and tissue distributions of compound 22 in mice revealed low plasma exposure and high concentrations in different segments of the intestine and liver, which may facilitate targeting DGAT-1...
July 14, 2017: Bioorganic & Medicinal Chemistry
https://www.readbyqxmd.com/read/28725265/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
#2
Nannan Zhang, Zejing Mao, Ling Luo, Xia Wan, Fenghong Huang, Yangmin Gong
BACKGROUND: 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)...
2017: Biotechnology for Biofuels
https://www.readbyqxmd.com/read/28703942/low-temperature-and-phosphate-deficiency-responsive-elements-control-dgtt3-expression-in-chlamydomonas-reinhardtii
#3
Xiaowen Fei, Ping Li, Xinghan Li, Xiaodong Deng
acyl-CoA:Diacylglycerol acyltransferases (DGAT) catalyse the final step of the triacylglycerol biosynthesis. Two major gene families have been shown to encode DGATs, DGAT1 and DGAT2. Abiotic factors such as low temperatures, nitrogen or phosphorus deficiency was reported to play important roles in the growth and development in green algae. Whether DGATs are induced by low temperatures or phosphorus deficiency, and the corresponding promoter elements are not reported yet. In this study, we found DGTT3 to have a significant response to low temperatures, phosphorus deficiency, and other stresses, such as high concentrations of NaCl, 20 μM GA, and 20 μM abscisic acid...
July 13, 2017: Journal of Eukaryotic Microbiology
https://www.readbyqxmd.com/read/28700690/inactivation-of-human-dgat2-by-oxidative-stress-on-cysteine-residues
#4
Sunhee Jung, Miri Choi, Kwangman Choi, Eun Bin Kwon, Mingu Kang, Dong-Eun Kim, Hyejeong Jeong, Janghwan Kim, Jong Heon Kim, Mun Ock Kim, Sang-Bae Han, Sungchan Cho
Diacylglycerol acyltransferases (DGATs) have a crucial role in the biosynthesis of triacylglycerol (TG), the major storage form of metabolic energy in eukaryotic organisms. Even though DGAT2, one of two distinct DGATs, has a vital role in TG biosynthesis, little is known about the regulation of DGAT2 activity. In this study, we examined the role of cysteine and its oxidation in the enzymatic activity of human DGAT2 in vitro. Human DGAT2 activity was considerably inhibited not only by thiol-modifying reagents (NEM and IA) but also by ROS-related chemicals (H2O2 and β-lapachone), while human DGAT1 and GPAT1 were little affected...
2017: PloS One
https://www.readbyqxmd.com/read/28694845/a-type-i-diacylglycerol-acyltransferase-modulates-triacylglycerol-biosynthesis-and-fatty-acid-composition-in-the-oleaginous-microalga-nannochloropsis-oceanica
#5
Hehong Wei, Ying Shi, Xiaonian Ma, Yufang Pan, Hanhua Hu, Yantao Li, Ming Luo, Henri Gerken, Jin Liu
BACKGROUND: Photosynthetic oleaginous microalgae are considered promising feedstocks for biofuels. The marine microalga, Nannochloropsis oceanica, has been attracting ever-increasing interest because of its fast growth, high triacylglycerol (TAG) content, and available genome sequence and genetic tools. Diacylglycerol acyltransferase (DGAT) catalyzes the last and committed step of TAG biosynthesis in the acyl-CoA-dependent pathway. Previous studies have identified 13 putative DGAT-encoding genes in the genome of N...
2017: Biotechnology for Biofuels
https://www.readbyqxmd.com/read/28672939/triptolide-suppresses-ultraviolet-b-enhanced-sebum-production-by-inhibiting-the-biosynthesis-of-triacylglycerol-in-hamster-sebaceous-glands-in-vivo-and-in-vitro
#6
Takashi Sato, Noriko Akimoto, Aiko Takahashi, Akira Ito
Ultraviolet B (UVB) irradiation causes alterations in cutaneous barrier function, including excessive production of sebum in sebaceous glands, which is associated with the aggravation of acne. This study aimed to evaluate the inhibitory effects of triptolide, a diterpenoid triepoxide from Tripterygium wilfordii Hook F, on sebocytic lipogenesis in UVB-irradiated hamster skin in vivo and in vitro. Topical application of triptolide decreased the UVB-enhanced sebum accumulation in the sebaceous glands of hamster skin...
July 2017: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/28649761/functional-assessment-of-plant-and-microalgal-lipid-pathway-genes-in-yeast-to-enhance-microbial-industrial-oil-production
#7
Huadong Peng, Lalehvash Moghaddam, Anthony Brinin, Brett Williams, Sagadevan Mundree, Victoria S Haritos
As promising alternatives to fossil-derived oils, microbial lipids are important as industrial feedstocks for biofuels and oleochemicals. Our broad aim is to increase lipid content in oleaginous yeast through expression of lipid accumulation genes and use Saccharomyces cerevisiae to functionally assess genes obtained from oil-producing plants and microalgae. Lipid accumulation genes DGAT (diacylglycerol acyltransferase), PDAT (phospholipid: diacylglycerol acyltransferase) and ROD1 (phosphatidylcholine: diacylglycerol choline-phosphotransferase) were separately expressed in yeast and lipid production measured by fluorescence, solvent extraction, TLC and GC of fatty acid methyl esters...
June 25, 2017: Biotechnology and Applied Biochemistry
https://www.readbyqxmd.com/read/28642195/how-lipid-droplets-tag-along-glycerolipid-synthetic-enzymes-and-lipid-storage
#8
REVIEW
Huan Wang, Michael V Airola, Karen Reue
Triacylglycerols (TAG) serve as the predominant form of energy storage in mammalian cells, and TAG synthesis influences conditions such as obesity, fatty liver, and insulin resistance. In most tissues, the glycerol 3-phosphate pathway enzymes are responsible for TAG synthesis, and the regulation and function of these enzymes is therefore important for metabolic homeostasis. Here we review the sites and regulation of glycerol-3-phosphate acyltransferase (GPAT), acylglycerol-3-phosphate acyltransferase (AGPAT), lipin/phosphatidic acid phosphatase (PAP), and diacylglycerol acyltransferase (DGAT) enzyme action...
June 19, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28641384/acute-testosterone-deficiency-alters-adipose-tissue-fatty-acid-storage
#9
Sylvia Santosa, Nikki C Bush, Michael D Jensen
Context: Although the long-term effects of testosterone on adipose tissue lipid metabolism in men have been defined, the short-term regulation of these effects is not well understood. Objective: We examined the effects of acute testosterone withdrawal on subcutaneous abdominal and femoral adipose tissue fatty acid (FA) storage and cellular mechanisms. Design: This was a prospective, randomized trial. Setting: Mayo Clinic Clinical Research Unit...
June 21, 2017: Journal of Clinical Endocrinology and Metabolism
https://www.readbyqxmd.com/read/28625352/rna-seq-and-metabolic-flux-analysis-of-tetraselmis-sp-m8-during-nitrogen-starvation-reveals-a-two-stage-lipid-accumulation-mechanism
#10
David K Y Lim, Holger Schuhmann, Skye R Thomas-Hall, Kenneth C K Chan, Taylor J Wass, Felipe Aguilera, T Catalina Adarme-Vega, Cristiana G O Dal'Molin, Glen J Thorpe, Jacqueline Batley, David Edwards, Peer M Schenk
To map out key lipid-related pathways that lead to rapid triacylglyceride accumulation in oleaginous microalgae, RNA-Seq was performed with Tetraselmis sp. M8 at 24h after exhaustion of exogenous nitrogen to reveal molecular changes during early stationary phase. Further gene expression profiling by quantitative real-time PCR at 16-72h revealed a distinct shift in expression of the fatty acid/triacylglyceride biosynthesis and β-oxidation pathways, when cells transitioned from log-phase into early-stationary and stationary phase...
June 6, 2017: Bioresource Technology
https://www.readbyqxmd.com/read/28615668/improving-the-detection-of-pathways-in-genome-wide-association-studies-by-combined-effects-of-snps-from-linkage-disequilibrium-blocks
#11
Huiying Zhao, Dale R Nyholt, Yuanhao Yang, Jihua Wang, Yuedong Yang
Genome-wide association studies (GWAS) have successfully identified single variants associated with diseases. To increase the power of GWAS, gene-based and pathway-based tests are commonly employed to detect more risk factors. However, the gene- and pathway-based association tests may be biased towards genes or pathways containing a large number of single-nucleotide polymorphisms (SNPs) with small P-values caused by high linkage disequilibrium (LD) correlations. To address such bias, numerous pathway-based methods have been developed...
June 14, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28577437/rutin-exhibits-hepatoprotective-effects-in-a-mouse-model-of-non-alcoholic-fatty-liver-disease-by-reducing-hepatic-lipid-levels-and-mitigating-lipid-induced-oxidative-injuries
#12
Qingsheng Liu, Ran Pan, Lei Ding, Fuli Zhang, Linfeng Hu, Bin Ding, Linwensi Zhu, Yongliang Xia, Xiaobing Dou
Nonalcoholic fatty liver disease (NAFLD) is characterized by excessive accumulation of hepatic lipids and oxidative injury of hepatocytes. Rutin is a natural flavonoid with significant roles in combating cellular oxidative stress and regulating lipid metabolism. The current study aims to investigate the molecular mechanisms underlying rutin's hypolipidemic and hepatoprotective effects in nonalcoholic fatty liver disease. Rutin treatment was applied to male C57BL/6 mice maintained on a high-fat diet and HepG2 cells challenged with oleic acid...
August 2017: International Immunopharmacology
https://www.readbyqxmd.com/read/28507704/elucidation-of-salicylate-attachment-in-celesticetin-biosynthesis-opens-the-door-to-create-a-library-of-more-efficient-hybrid-lincosamide-antibiotics
#13
S Kadlcik, Z Kamenik, D Vasek, M Nedved, J Janata
Lincosamides, which are produced by streptomycetes, compose a small but clinically important class of antibiotics. The recent elucidation of the condensation and post-condensation biosynthetic steps of the lincosamides lincomycin and celesticetin revealed several unexpected reaction mechanisms. Here, we prepared recombinant proteins involved in the celesticetin biosynthetic pathway and used them for in vitro assays that were monitored by LC-MS. Our results elucidate the last biosynthetic step of celesticetin: the attachment of salicylic acid is catalyzed by the Ccb2 acyl-CoA ligase and the Ccb1 acyltransferase...
May 1, 2017: Chemical Science
https://www.readbyqxmd.com/read/28465060/biosynthesis-of-the-fatty-acid-isopropyl-esters-by-engineered-escherichia-coli
#14
Hong Pan, Lihua Zhang, Xun Li, Daoyi Guo
The fatty acid methyl esters and fatty acid ethyl esters are known as biodiesels which are considered to be renewable, nontoxic and biodegradable biofuels. However, the conventional biodiesels show a high crystallization temperature which is one of the most critical obstacles against the widespread biodiesel usage. The high crystallization temperature of biodiesel can be reduced by replacing the methyl or ethyl ester with an isopropyl moiety. Here we report on a strategy to establish biosynthesis of the fatty acid isopropyl esters(FAIPEs) from the simple substrate glucose in Escherichia coli with heterologous coexpression of atoB encoded acetyl-CoA acetyltransferase and atoAD encode acetoacetyl-CoA transferase from E...
July 2017: Enzyme and Microbial Technology
https://www.readbyqxmd.com/read/28455945/the-influence-of-delipidation-on-triglyceride-and-lipin1-of-porcine-embryos-derived-from-parthenogenetic-activation
#15
Y Zeng, C Wang, Y Niu, D Chi, M Xu, L Si, X Qu, J Li
Proteins in the LIPIN family play key roles in lipid synthesis mainly on triacylglycerol (TAG) biosynthesis, and they also act as transcriptional coactivators to regulate the expression of genes involved in lipid metabolism with other nuclear factors. Hence, this study was designed to investigate LIPIN1 in pig oocytes and embryos by the delipidation. After delipidation, the content of lipids (LDs) and TAG in MII oocyte was significantly reduced; however, a similar increasing tendency of TAG was shown during embryos development...
April 29, 2017: Reproduction in Domestic Animals, Zuchthygiene
https://www.readbyqxmd.com/read/28448543/heterologous-expression-of-a-thermophilic-diacylglycerol-acyltransferase-triggers-triglyceride-accumulation-in-escherichia-coli
#16
Beatriz Lázaro, Juan A Villa, Omar Santín, Matilde Cabezas, Cintia D F Milagre, Fernando de la Cruz, Gabriel Moncalián
Triglycerides (TAGs), the major storage molecules of metabolic energy and source of fatty acids, are produced as single cell oil by some oleogenic microorganisms. However, these microorganisms require strict culture conditions, show low carbon source flexibilities, lack efficient genetic modification tools and in some cases pose safety concerns. TAGs have essential applications such as behaving as a source for added-value fatty acids or giving rise to the production of biodiesel. Hence, new alternative methods are urgently required for obtaining these oils...
2017: PloS One
https://www.readbyqxmd.com/read/28328322/novel-lc-ms-ms-and-high-throughput-mass-spectrometric-assays-for-monoacylglycerol-acyltransferase-inhibitors
#17
Jenson Qi, John A Masucci, Wensheng Lang, Margery A Connelly, Gary W Caldwell, Ioanna Petrounia, Jennifer Kirkpatrick, Alexander N Barnakov, Geoffrey Struble, Robyn Miller, Keli Dzordzorine, Gee-Hong Kuo, Michael Gaul, Alessandro Pocai, Seunghun Lee
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)...
April 2017: SLAS Discovery
https://www.readbyqxmd.com/read/28325847/a-specialized-diacylglycerol-acyltransferase-contributes-to-the-extreme-medium-chain-fatty-acid-content-of-cuphea-seed-oil
#18
Umidjon Iskandarov, Jillian E Silva, Hae Jin Kim, Mariette Andersson, Rebecca E Cahoon, Keithanne Mockaitis, Edgar B Cahoon
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)...
May 2017: Plant Physiology
https://www.readbyqxmd.com/read/28274201/analysis-of-triglyceride-synthesis-unveils-a-green-algal-soluble-diacylglycerol-acyltransferase-and-provides-clues-to-potential-enzymatic-components-of-the-chloroplast-pathway
#19
Carolina Bagnato, María B Prados, Gisela R Franchini, Natalia Scaglia, Silvia E Miranda, María V Beligni
BACKGROUND: Microalgal triglyceride (TAG) synthesis has attracted considerable attention. Particular emphasis has been put towards characterizing the algal homologs of the canonical rate-limiting enzymes, diacylglycerol acyltransferase (DGAT) and phospholipid:diacylglycerol acyltransferase (PDAT). Less work has been done to analyze homologs from a phylogenetic perspective. In this work, we used HMMER iterative profiling and phylogenetic and functional analyses to determine the number and sequence characteristics of algal DGAT and PDAT, as well as related sequences that constitute their corresponding superfamilies...
March 9, 2017: BMC Genomics
https://www.readbyqxmd.com/read/28247196/identification-and-characterization-of-a-novel-diacylglycerol-acyltransferase-gene-from-mortierella-alpina
#20
Xin-An Luo, Yuan-Min Zhu, Ting-Ting Liu, Xiao-Peng Wang, Peng-Peng Zhou, Zhen-Dong Bao, Long-Jiang Yu
OBJECTIVES: To clone and express a diacylglycerol acyltransferase (DGAT) gene from Mortierella alpina in Saccharomyces cerevisiae and characterize oil production and fatty acid composition of the resulting recombinant RESULTS: A new, full-length cDNA, putatively encoding a DGAT, was cloned from M. alpina. We subsequently cloned the gene, except the transmembrane-encoding region, termed MaDGAT, its molecular mass was 31.3 kDa. MaDGAT shares 75% identity with a DGAT from Mortierella verticillata NRRL 6337...
February 28, 2017: Biotechnology Letters
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