• Archives of Pharmacal Research
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• v.28 no.2
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• pp.164-168
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• 2005

The EtOAc extract of Youngia koidzumiana significantly inhibited the diacylglycerol acyltransferase (DGAT) from rat liver microsomes. Bioactivity-guided fractionation led to the isolation of nine compounds, the structures of which were established using physicochemical and spectral data. Of the isolated compounds, oleanolic acid (2), methyl ursolate (7) and corosolic aicd (8) inhibited DGAT, with $IC_{50}$ values of 31.7, 26.4, and $44.3{\mu}M$, respectively. However, sesquit-erpenoids showed only weak inhibitory effects toward DGAT.

• Archives of Pharmacal Research
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• v.25 no.4
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• pp.446-448
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• 2002

The inhibitory activity of tanshinones from Salvia miltiorrhiza was tested on rat liver diacylglycerol acyltransferase (DGAT). Cryptotanshinone (1) and 15,16-dihydrotanshinone I (3) exhibited potent DGAT inhibitory activities dose-dependently with $IC_{50}$ values of $10.5 {\;}{\mu\textrm{g}}/ml{\;}and{\;}11.1{\;}{\mu\textrm{g}}/ml$. However, tanshinone IIA (2) and tanshinone I (4) showed very weak inhibition ($IC_{50}{\;}value:{\;}>{\;}250{\;}{\mu\textrm{g}}/ml$). A dihydrofuran moiety was seemed to be responsible for the stronger inhibitory activity

• Korean Journal of Pharmacognosy
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• v.32 no.3 s.126
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• pp.193-199
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• 2001

The inhibitory effects of methanol extracts of 135 medicinal herbs on diacylglycerol acyltransferase (DGAT) activity were investigated. DGAT was partially purified from rat liver. Eleven kinds of methanol extracts of medicinal herbs including Evodiae Fructus showed a mild inhibitory effect with the concentration of $125\;{\mu}g/ml$ (above 40% inhibition). Six kinds of methanol extracts including Ephedrae Herba exhibited a weak inhibition. Among them, three kinds of butanol extracts (Sophorae Radix, Arecae Semen, Caesalpiniae Lignum) and the chloroform extracts of Evodiae Fructus showed significant inhibitory activities (above 60% inhibition) at the same concentration.

• Proceedings of the PSK Conference
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• 2002.10a
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• pp.375.4-376
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• 2002

Acyl CoA:diacylglycerol acyltransferase (DGAT) is a key enzyme involved in triacylglycerol synthesis. Too much accumulation of triacylglycerol in certain organs and tissues of the body causes high risk conditions of fatty liver. obesity and hypertriglyceridemia. leading to serious diseases of atherosclerosis. Therefore, DGAT inhibition may be worthwhile strategy for the treatment of triglyceride metabolism disorders. such as obesity or hypertriglyceridemia. (omitted)

• Proceedings of the PSK Conference
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• 2003.04a
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• pp.267.1-267.1
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• 2003

Diacylglycerol acyltransferase (DGAT) is a microsomal enzyme that plays a central role in the metabolism of cellular glycerolipid. Recently, the generation of DGA T-deficient mice has provided a better understanding of triglyceride synthesis and its relationship to obesity. Therefore DGAT is an attractive target for treatments of triglyceride metabolism disorders, such as obesity or hypertriglyceridemia. (omitted)

• Journal of Microbiology and Biotechnology
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• v.18 no.11
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• pp.1785-1788
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• 2008

Phenylpyropenes A, B, and C, isolated from Penicillium griseofulvum F1959, inhibited DGAT in rat liver microsomes with $IC_{50}$ values of $78.7{\pm}1.6$, $21.7{\pm}0.2$, and $11.04{\pm}0.2{\mu}M$, respectively. In addition, a kinetic analysis using a Lineweaver-Burk plot revealed that phenylpyropene C was a noncompetitive inhibitor of DGAT. The apparent Michaelis constant ($K_m$) value and inhibition constant ($K_i$) value were calculated to be $8{\mu}M$ and $10.48{\mu}M$, respectively. Moreover, phenylpyropene C inhibited triglyceride formation in HepG2 cells.

• Journal of the Korean Data and Information Science Society
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• v.26 no.6
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• pp.1249-1258
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• 2015

DGAT1(diacylglycerol O-acyltransferase1) gene is well known as a major gene of milk production in dairy cattle. This study was conducted to investigate how the DGAT1 gene effect on milk yield was appeared from the genome wide association (GWA) using high density whole genome SNP chip. The data set used in this study consisted of 353 Korean Holstein sires with 50k SNP genotypes and deregressed estimated breeding values of milk yield. After quality control 41,051 SNPs were selected and locations on chromosome were mapped using UMD 3.1. Bayesian regression of BayesB method (pi=0.99) was used to estimate the SNP effects and genomic breeding values. Percentages of variance explained by 1 Mb non-overlapping windows were calculated to detect the QTL region. As the result of this study, top 1 and 3 of 2,516 windows were seen around DGAT1 gene region and 0.51% and 0.48% of genetic variance were explained by these two windows. Although SNPs on the DGAT1 gene region are excluded in commercial 50k SNP chip, the effect of DGAT1 gene seem to be reflected on GWA by the SNPs which are in linkage disequilibrium with DGAT1 gene.

• BMB Reports
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• v.50 no.7
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• pp.367-372
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• 2017

Monoacylglycerol acyltransferase 1 (MGAT) is a microsomal enzyme that catalyzes the synthesis of diacylglycerol (DAG) and triacylglycerol (TAG). However, the subcellular localization and catalytic function domain of this enzyme is poorly understood. In this report, we identified that murine MGAT1 localizes to the endoplasmic reticulum (ER) under normal conditions, whereas MGAT1 co-localize to the lipid droplets (LD) under conditions of enriching fatty acids, contributing to TAG synthesis and LD expansion. For the enzyme activity, both the N-terminal transmembrane domain and catalytic HPHG motif are required. We also show that the transmembrane domain of MGAT1 consists of two hydrophobic regions in the N-terminus, and the consensus sequence FLXLXXXn, a putative neutral lipid-binding domain, exists in the first transmembrane domain. Finally, MGAT1 interacts with DGAT2, which serves to synergistically increase the TAG biosynthesis and LD expansion, leading to enhancement of lipid accumulation in the liver and fat.

• Natural Product Sciences
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• v.17 no.2
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• pp.117-122
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• 2011

We investigated the effect of Orostachys japonicus extracts on serum lipids, leptin and insulin level in hyperlipidemic rats. Also, diacylglycerol acyltransferase (DGAT) activity and thiobarbituric acid reactive substance (TBARS) were assessed. Inhibitory effect of DGAT related to triglyceride synthesis emerged approximately 96% in EtOAc fraction and showed 90% and 67%, respectively, in CHCl3 and BuOH fractions. Furthermore, the EtOAc and BuOH fractions inhibited 81% and 77%, respectively, in glycerol-3-phosphate acyl transferase (GPAT). Hyperlipidemia and obesity marker, contents of leptin and insulin on serum of hyperlipidemic rats, decreased 50% and 25%, respectively, compared with control group in treated EtOAc fraction. The oxidative stress marker, a concentration of TBARS, showed decrease of approximately 30% in treated EtOAc fraction. Moreover, high density lipoprotein (HDL)-cholesterol contents on serum of rats fed a hyperlipidemic diet were increased 10% and low density lipoprotein (LDL)-cholesterol decreased 50% as well as triglyceride amount of feces multiplied approximately two times more than control group in treated EtOAc fraction. The data suggest that the fractions of O. japonicus may be a potent biomaterial for treatment of hyperlipidemia or obesity.

• Journal of Microbiology and Biotechnology
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• v.33 no.12
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• pp.1563-1575
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• 2023

Acyl-coenzyme A (CoA):diacylglycerol acyltransferase 2 (DGAT2) catalyzes the last stage of triacylglycerol (TAG) synthesis, a process that forms ester bonds with diacylglycerols (DAG) and fatty acyl-CoA substrates. The enzymatic role of Dgat2 has been studied in various biological species. Still, the full description of how Dgat2 channels fatty acids in skeletal myocytes and the consequence thereof in glucose uptake have yet to be well established. Therefore, this study explored the mediating role of Dgat2 in glucose uptake and fatty acid partitioning under short interfering ribonucleic acid (siRNA)-mediated Dgat2 knockdown conditions. Cells transfected with Dgat2 siRNA downregulated glucose transporter type 4 (Glut4) messenger RNA (mRNA) expression and decreased the cellular uptake of [1-¹⁴C]-labeled 2-deoxyglucose up to 24.3% (p < 0.05). Suppression of Dgat2 deteriorated insulin-induced Akt phosphorylation. Dgat2 siRNA reduced [1-¹⁴C]-labeled oleic acid incorporation into TAG, but increased the level of [1-¹⁴C]-labeled free fatty acids at 3 h after initial fatty acid loading. In an experiment of chasing radioisotope-labeled fatty acids, Dgat2 suppression augmented the level of cellular free fatty acids. It decreased the level of re-esterification of free fatty acids to TAG by 67.6% during the chase period, and the remaining pulses of phospholipids and cholesteryl esters were decreased by 34.5% and 61%, respectively. Incorporating labeled fatty acids into beta-oxidation products increased in Dgat2 siRNA transfected cells without gene expression involving fatty acid oxidation. These results indicate that Dgat2 has regulatory function in glucose uptake, possibly through the reaction of TAG with endogenously released or recycled fatty acids.