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https://www.readbyqxmd.com/read/29050877/diacylglycerol-acyltransferase-2-of-mortierella-alpina-with-specificity-on-long-chain-polyunsaturated-fatty-acids-a-potential-tool-for-reconstituting-lipids-with-nutritional-value
#1
Sukanya Jeennor, Mayura Veerana, Jutamas Anantayanon, Sarocha Panchanawaporn, Chanikul Chutrakul, Kobkul Laoteng
Based on available genome sequences and bioinformatics tools, we searched for an uncharacterized open reading frame of Mortierella alpina (MaDGAT2) using diacylglycerol acyltransferase sequence (fungal DGAT type 2B) as a query. Functional characterization of the identified native and codon-optimized M. alpina genes were then performed by heterologous expression in Saccharomyces cerevisiae strain defective in synthesis of neutral lipid (NL). Lipid analysis of the yeast tranformant carrying MaDGAT2 showed that the NL biosynthesis and lipid particle formation were restored by the gene complementation...
October 16, 2017: Journal of Biotechnology
https://www.readbyqxmd.com/read/29042644/hiv-1-viral-protein-r-vpr-induces-fatty-liver-in-mice-via-lxr%C3%AE-and-ppar%C3%AE-dysregulation-implications-for-hiv-specific-pathogenesis-of-nafld
#2
Neeti Agarwal, Dinakar Iyer, Chiara Gabbi, Pradip Saha, Sanjeet G Patel, Qianxing Mo, Benny Chang, Biman Goswami, Ulrich Schubert, Jeffrey B Kopp, Dorothy E Lewis, Ashok Balasubramanyam
HIV patients develop hepatic steatosis. We investigated hepatic steatosis in transgenic mice expressing the HIV-1 accessory protein Vpr (Vpr-Tg) in liver and adipose tissues, and WT mice infused with synthetic Vpr. Vpr-Tg mice developed increased liver triglyceride content and elevated ALT, bilirubin and alkaline phosphatase due to three hepatic defects: 1.6-fold accelerated de novo lipogenesis (DNL), 45% slower fatty acid ß-oxidation, and 40% decreased VLDL-triglyceride export. Accelerated hepatic DNL was due to coactivation by Vpr of liver X receptor-α (LXRα) with increased expression of its lipogenic targets Srebp1c, Chrebp, Lpk, Dgat, Fasn and Scd1, and intranuclear SREBP1c and ChREBP...
October 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29031100/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
#3
Ling Zheng, Jay Shockey, Feng Guo, Lingmin Shi, Xinguo Li, Lei Shan, Shubo Wan, Zhenying Peng
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...
October 6, 2017: Journal of Plant Physiology
https://www.readbyqxmd.com/read/28900030/multiple-mechanisms-contribute-to-increased-neutral-lipid-accumulation-in-yeast-producing-recombinant-variants-of-plant-diacylglycerol-acyltransferase-1
#4
Yang Xu, Guanqun Chen, Michael S Greer, Kristian Mark P Caldo, Geetha Ramakrishnan, Saleh Shah, Limin Wu, M Joanne Lemieux, Jocelyn Ozga, Randall J Weselake
The apparent bottleneck in the accumulation of oil during seed development in some oleaginous plant species is the formation of triacylglycerol (TAG) by the acyl-CoA-dependent acylation of sn-1,2-diacylglycerol catalyzed by diacylglycerol acyltransferase (DGAT, EC 2.3.1.20). Improving DGAT activity using protein engineering could lead to improvements in seed oil yield (e.g. in canola-type Brassica napus). Directed evolution of B. napus DGAT1 (BnaDGAT1) previously revealed that one of the regions where amino acid residue substitutions lead to higher performance in BnaDGAT1 is in the ninth predicted transmembrane domain (PTMD9)...
October 27, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28877685/positive-regulation-of-prostate-cancer-cell-growth-by-lipid-droplet-forming-and-processing-enzymes-dgat1-and-abhd5
#5
Ranjana Mitra, Thuc T Le, Priyatham Gorjala, Oscar B Goodman
BACKGROUND: Neoplastic cells proliferate rapidly and obtain requisite building blocks by reprogramming metabolic pathways that favor growth. Previously, we observed that prostate cancer cells uptake and store lipids in the form of lipid droplets, providing building blocks for membrane synthesis, to facilitate proliferation and growth. Mechanisms of lipid uptake, lipid droplet dynamics and their contribution to cancer growth have yet to be defined. This work is focused on elucidating the prostate cancer-specific modifications in lipid storage pathways so that these modified gene products can be identified and therapeutically targeted...
September 6, 2017: BMC Cancer
https://www.readbyqxmd.com/read/28874574/effect-of-cell-cycle-arrest-on-intermediate-metabolism-in-the-marine-diatom-phaeodactylum-tricornutum
#6
Joomi Kim, Christopher M Brown, Min Kyung Kim, Elizabeth H Burrows, Stéphane Bach, Desmond S Lun, Paul G Falkowski
The inhibitor NU 2058 [6-(cyclohexylmethoxy)-9H-purin-2-amine] leads to G1-phase cell cycle arrest in the marine diatom, Phaeodactylum tricornutum, by binding to two cyclin-dependent kinases, CDKA1 and CDKA2. NU 2058 has no effect on photosynthetic attributes, such as Fv/Fm, chlorophyll a/cell, levels of D2 PSII subunits, or RbcL; however, cell cycle arrest leads to unbalanced growth whereby photosynthetic products that can no longer be used for cell division are redirected toward carbohydrates and triacylglycerols (TAGs)...
September 19, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28818386/heterologous-expression-of-two-gpats-from-jatropha-curcas-alters-seed-oil-levels-in-transgenic-arabidopsis-thaliana
#7
Aparna Misra, Kasim Khan, Abhishek Niranjan, Vinod Kumar, Vidhu A Sane
Oils and fats are stored in endosperm during seed development in the form of triacylglycerols. Three acyltransferases: glycerol-3-phosphate acyltransferase (GPAT), lysophosphatidyl acyltransferase (LPAT) and diacylglycerol acyltransferase (DGAT) are involved in the storage lipid biosynthesis and catalyze the stepwise acylation of glycerol backbone. In this study two members of GPAT gene family (JcGPAT1 and JcGPAT2) from Jatropha seeds were identified and characterized. Sequence analysis suggested that JcGPAT1 and JcGPAT2 are homologous to Arabidopsis acyltransferase-1 (ATS1) and AtGPAT9 respectively...
October 2017: Plant Science: An International Journal of Experimental Plant Biology
https://www.readbyqxmd.com/read/28768178/triglyceride-synthesis-by-dgat1-protects-adipocytes-from-lipid-induced-er-stress-during-lipolysis
#8
Chandramohan Chitraju, Niklas Mejhert, Joel T Haas, L Grisell Diaz-Ramirez, Carrie A Grueter, Jason E Imbriglio, Shirly Pinto, Suneil K Koliwad, Tobias C Walther, Robert V Farese
Triglyceride (TG) storage in adipose tissue provides the major reservoir for metabolic energy in mammals. During lipolysis, fatty acids (FAs) are hydrolyzed from adipocyte TG stores and transported to other tissues for fuel. For unclear reasons, a large portion of hydrolyzed FAs in adipocytes is re-esterified to TGs in a "futile," ATP-consuming, energy dissipating cycle. Here we show that FA re-esterification during adipocyte lipolysis is mediated by DGAT1, an ER-localized DGAT enzyme. Surprisingly, this re-esterification cycle does not preserve TG mass but instead functions to protect the ER from lipotoxic stress and related consequences, such as adipose tissue inflammation...
August 1, 2017: Cell Metabolism
https://www.readbyqxmd.com/read/28763157/a-unifying-mathematical-model-of-lipid-droplet-metabolism-reveals-key-molecular-players-in-the-development-of-hepatic-steatosis
#9
Christin Wallstab, Dimitra Eleftheriadou, Theresa Schulz, Georg Damm, Daniel Seehofer, Jürgen Borlak, Hermann-Georg Holzhütter, Nikolaus Berndt
The liver responds to elevated plasma concentrations of free fatty acids (FFAs) with an enhanced uptake of FFAs and their esterification to triacylglycerol (TAG). On the long term, this may result in massive hepatic TAG accumulation called steatosis hepatitis. In hepatocytes, the poor water-soluble TAG is packed in specialized organelles: Lipid droplets (LDs) serving as transient cellular deposit and lipoproteins (LPs) transporting TAG and cholesterol esters to extra-hepatic tissues. The dynamics of these organelles is controlled by a variety of regulatory surface proteins (RSPs)...
October 2017: FEBS Journal
https://www.readbyqxmd.com/read/28739155/discovery-of-a-low-systemic-exposure-dgat-1-inhibitor-with-a-picolinoylpyrrolidine-2-carboxylic-acid-moiety
#10
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...
September 1, 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
#11
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
#12
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
#13
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
#14
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
#15
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
#16
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
#17
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...
October 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28641384/acute-testosterone-deficiency-alters-adipose-tissue-fatty-acid-storage
#18
RANDOMIZED CONTROLLED TRIAL
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...
August 1, 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
#19
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...
November 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
#20
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
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