• 제목/요약/키워드: Fatty acid synthase

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Effects of Genistein Supplementation on Fatty Liver and Lipid Metabolism in Rats Fed High Fat Diet (고지방식이를 섭취하는 흰 쥐에서 제니스테인 보충이 지방간 및 지질대사에 미치는 영향)

  • Lee, Seon-Hye;Kim, Mi-Hyun;Park, Mi-Na;Lee, Yeon-Sook
    • Journal of Nutrition and Health
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    • v.40 no.8
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    • pp.693-700
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    • 2007
  • This study was performed to investigate the effects of genistein, a kind of soy isoflavones, on fatty liver and lipid metabolism in rats fed high fat diet. Twenty four male Sprague-Dawley rats were divided into four groups by dietary fat and genistein contents then raised for six weeks. The rats(n=6/group) were fed normal fat diet(NOR), high fat diet (HF), high fat with 0.1% genistein(HF+0.1%G) or high fat with 0.2% genistein(HF+0.2%G). Hepatic total lipid, triglyceride, total cholesterol and Serum GPT, as a marker for fatty liver, were significantly increased by high fat diet. Also, serum total lipid, triglyceride, total cholesterol, glucose and insulin concentration, hepatic lipogenic enzyme (fatty acid synthase and malic enzyme) activities were significantly increased by high fat diet. However, hepatic total lipid, triglyceride, total cholesterol and Serum GPT were significantly decreased by genistein intake. Also, genistein supplementation decreased serum total lipid, triglyceride, glucose and insulin concentration, hepatic lipogenic enzyme (fatty acid synthase and malic enzyme) activities. There were no differences by genistein level except for serum insulin. These results suggest that fatty liver induced by high fat diet was caused by increased serum lipid profiles and hepatic lipogenesis, whereas, genistein may be useful in inhibiting of fatty liver by reducing serum lipid profiles and hepatic lipogenesis.

Comparative Modeling and Molecular Dynamics Simulation of Substrate Binding in Human Fatty Acid Synthase: Enoyl Reductase and β-Ketoacyl Reductase Catalytic Domains

  • John, Arun;Umashankar, Vetrivel;Krishnakumar, Subramanian;Deepa, Perinkulam Ravi
    • Genomics & Informatics
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    • v.13 no.1
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    • pp.15-24
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    • 2015
  • Fatty acid synthase (FASN, EC 2.3.1.85), is a multi-enzyme dimer complex that plays a critical role in lipogenesis. This lipogenic enzyme has gained importance beyond its physiological role due to its implications in several clinical conditions-cancers, obesity, and diabetes. This has made FASN an attractive pharmacological target. Here, we have attempted to predict the theoretical models for the human enoyl reductase (ER) and ${\beta}$-ketoacyl reductase (KR) domains based on the porcine FASN crystal structure, which was the structurally closest template available at the time of this study. Comparative modeling methods were used for studying the structure-function relationships. Different validation studies revealed the predicted structures to be highly plausible. The respective substrates of ER and KR domains-namely, trans-butenoyl and ${\beta}$-ketobutyryl-were computationally docked into active sites using Glide in order to understand the probable binding mode. The molecular dynamics simulations of the apo and holo states of ER and KR showed stable backbone root mean square deviation trajectories with minimal deviation. Ramachandran plot analysis showed 96.0% of residues in the most favorable region for ER and 90.3% for the KR domain, respectively. Thus, the predicted models yielded significant insights into the substrate binding modes of the ER and KR catalytic domains and will aid in identifying novel chemical inhibitors of human FASN that target these domains.

Effects of Dietary Energy Density on Growth, Carcass Quality and mRNA Expression of Fatty Acid Synthase and Hormone-sensitive Lipase in Finishing Pigs

  • Liu, Z.H.;Yang, F.Y.;Kong, L.J.;Lai, C.H.;Piao, X.S.;Gu, Y.H.;Ou, X.Q.
    • Asian-Australasian Journal of Animal Sciences
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    • v.20 no.10
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    • pp.1587-1593
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    • 2007
  • A single factorial experiment was conducted to test the effects of three dietary levels of energy on mRNA expression of fatty acid synthase (FAS-mRNA) and hormone-sensitive lipase (HSL-mRNA) and their association with intramuscular fat in finishing pigs. 72 crossbred (Large $White{\times}Rongchang$) barrows with an average initial body weight of 20.71 (s.e. 0.1) kg, were randomly allotted to three dietary treatments (11.75, 13.05 and 14.36 MJ DE/kg) and fed until slaughtered at 100 or 101 kg. The diets were iso-nitrogenous and iso-essential amino acids. The growth performances including the duration of finishing were changed linearly (p<0.05) or quadratically (p<0.05) with increased dietary energy levels. The effects of dietary energy content on the percentage of external fat, intramuscular backfat and the fat thickness were linear (p<0.05). The content of dietary energy increased FAS-mRNA linearly or quadratically, while HSL-mRNA decreased linearly or quadratically in backfat and Longissmus dorsi muscle. Meanwhile, significant positive correlations (p<0.05) were found between energy level and intramuscular fat, FAS-mRNA or the ratio of FAS-mRNA to HSL-mRNA, between the ratio of FAS-mRNA to HSL-mRNA and intramuscular fat. However, the correlations between HSL mRNA and dietary energy or intramuscular fat were negative (p<0.05). The results indicated that dietary energy level regulates lipid accumulation, especially intramuscular fat, possibly by modulating the mRNA of FAS and HSL together rather than individually.

Protective Effects of Some Plant Extracts on Lipids Contents of Rats Treated with Carbon Tetrachloride (사염화탄소를 투여한 흰쥐의 지질농도에 미치는 식물추출물의 보호효과)

  • 최용순;김성완
    • Korean Journal of Plant Resources
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    • v.13 no.3
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    • pp.171-178
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    • 2000
  • This study was performed to investigate the possible effects of some plants protecting intact rat liver damaged by $CCl_4$. The extract of mugwort (Artemsiae capillaris), soybean sprout and pine leaf (Pinus strobus) inhibited markedly the in vitro activities of rat liver fatty acid synthase, whereas those of shiitake (Lentinus ododes), Houttuynia cortata, Acanthopanacis cortex and buckwheat leaves had less effects. Treatment with the water extract of pine leaf and soybean sprout caused a marked decrease in the $CCl_4$-induced toxicity in rat liver, judged from their effects on the levels of glutamic oxaloacetic transaminase (GOT) and glutamate pyruvic transaminase(GPT) in the serum. The extract of mugwort and soybean sprout reduced markedly the content of liver microsomal peroxides induced by $CCl_4$ treatment and serum TBA values, respectively. The extract of soybean sprout decreased efficiently the content of liver triglyceride elevated by $CCl_4$ treatment. Nevertheless, the extracts did not exert the supression of hepaticmegaly induced by $CCl_4$. The results suggest that soybean sprout and pine leaf may be potential sources improved the biochemical parameters like as peroxidation value or serum GOT and GPT, although these extracts had minimal effects in the increase of liver size induced by carbon tetrachloride.

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Effects of Growth Hormone Gene Polymorphism on Lipogenic Gene Expression Levels in Diaphragm Tissues of Japanese Black Heifers

  • Ardiyanti, Astrid;Abe, Tsuyoshi;Tameoka, Nanae;Kobayashi, Eiji;Shoji, Noriaki;Ohtani, Yoshihisa;Suzuki, Keiichi;Roh, Sang-Gun;Katoh, Kazuo
    • Asian-Australasian Journal of Animal Sciences
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    • v.25 no.8
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    • pp.1055-1062
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    • 2012
  • Two SNPs, i.e. L127V and T172M, of bovine growth hormone (GH) causing the presence of GH gene haplotypes A, B, and C was previously shown to alter intramuscular fatty acid (FA) composition in Japanese Black (JB) heifers. To determine the SNP effect on somatotropic hormone concentration and lipogenesis, we measured plasma GH, insulin, and insulin-like growth factor-1 (IGF-1) concentrations. We also measured mRNA levels of fatty acid synthase (FASN), stearoyl-coA desaturase (SCD), and sterol regulatory element binding proteins-1 (SREBP-1) and FA composition in diaphragm tissues. Heifers with genotype CC had the lowest plasma insulin concentration and FASN and SCD mRNA levels among genotypes. FASN mRNA levels in haplotype A tended to positively correlate with saturated FA (SFA) content and negatively correlated with C18:2 and unsaturated FA (USFA) contents. SCD mRNA levels in haplotype A positively correlated with monounsaturated FA (MUFA) contents and negatively correlated with C18:0 content. They also tended to positively correlate with C16:1, C18:1, and USFA contents and USFA/SFA ratio and negatively correlate with SFA content. Taken together, GH gene polymorphism affects the lipogenic genes expression levels and their relationships with fatty acid compositions in diaphragm tissues of JB heifers at 31 months of age.

MaoC Mediated Biosynthesis of Medium-chain-length Polyhydroxyalkanoates in Recombinant Escherichia coli from Fatty Acid (재조합 대장균에서 MaoC를 이용한 지방산으로부터의 중간사슬길이 폴리하이드록시알칸산 생산 연구)

  • Park, Si Jae;Lee, Seung Hwan;Oh, Young Hoon;Lee, Sang Yup
    • KSBB Journal
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    • v.29 no.4
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    • pp.244-249
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    • 2014
  • Biosynthesis pathway of medium-chain-length (MCL) polyhydroxyalkanoates (PHA) from fatty acid ${\beta}$-oxidation pathway was constructed in recombinant Escherichia coli by introducing the Pseudomonas sp. 61-3 PHA synthase gene (phaC2) and the maoC genes from Pseudomonas putida, Sinorhizobium meliloti, and Ralstonia eutropha. The metabolic link between fatty acid ${\beta}$-oxidation pathway and PHA biosynthesis pathway was constructed by MaoC, which is homologous to P. aeruginosa (R)-specific enoyl-CoA hydratase (PhaJ1). When the E. coli W3110 strains expressing the phaC2 gene and one of the maoC genes from P. putida, Sinorhizobium meliloti, and Ralstonia eutropha were cultured in LB medium containing 2 g/L of sodium decanoate as a carbon source, MCL-PHA that mainly consists of 3-hydroxyhexanoate (3HHx), 3-hydroxyoctanoate (3HO) and 3-hydroxydecanoate (3HD), was produced. The monomer composition of PHA and PHA contents varied depending on MaoC employed for the production of PHA. The highest PHA content of 18.7 wt% was achieved in recombinant E. coli W3110 expressing the phaC2 gene and the P. putida maoC gene. These results suggest that MCL-PHA biosynthesis pathway can be constructed in recombinant E. coli strains from the b-oxidation pathway by employing MaoC able to supply (R)-3-hydroxyacyl-CoA, the substrate of PHA synthase.

Anti-hyperlipidemic Effects of Scutellariae Radix, Aucklandiae Radix and Bupleuri Radix (SAB) extract in FL83B cells (지방간 유도 세포모델에서 황금(黃芩), 목향(木香), 시호(柴胡) 복합 추출물의 이상지질혈증에 대한 효과)

  • Do, Hyun Ju;Kim, Kyungho;Oh, Tae Woo
    • The Korea Journal of Herbology
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    • v.35 no.5
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    • pp.23-31
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    • 2020
  • Objectives : This study was conducted to evaluate the anti-hyperlipidemia effect of Scutellariae Radix, Aucklandiae Radix and Bupleuri Radix(SAB). Methods : FL83B cells were mouse liver hepatocytes, and we used this cell line. FL83B cells were treated with 0.5 mM oleic acid(OA) for 24 h, SAB extract was treated. After OA treatment, intracellular triglyceride (TG) and free fatty acid contents were measured with AdiopoRed™ assay and Free Fatty Acid Quantitation assay kit, respectively. Further, we evaluated several lipogenesis and metabolic markers such as sterol regulatory element-binding transcription factor-1c (SREBP-1c), acetyl-CoA carboxylase (ACC), fatty acid synthase (FAS), 3-hydroxy3-methyl-glutaryl CoA reductase (HMGCR), hormone-sensitive lipase (HSL), carnitine palmitoyltransferase (CPT-1), peroxisome proliferator activated receptor alpha (PPARα), and cluster of differentiation (CD36) using RT-PCR and Western-blot analysis. Results : OA markedly increased intracellular TG and free fatty acid, which plays a key role in reducing hepatic lipid accumulation, in FL83B cells. These increases were alleviated by SAB extract. The mRNA and protein expression of Fatty acid(FA) oxidation factors (CPT-1, PPARα), lipolysis factor(HSL), FA transporter(CD36), cholesterol synthesis factors (HMGCoA) and Lipodenesis (SREBP-1c, FAS, and ACC-1) were significantly increased by treatment of SAB extract in the OA-induced fatty liver cell model. Conclusions : In summary, the treat of SAB extract showed a significant reduction of the influx of fatty acids into hepatocytes, promoted the oxidation of fatty acids, and regulated fat synthesis-related factors, thereby regulating the accumulation of TG and free fatty acids.

Relationships between Single Nucleotide Polymorphism Markers and Meat Quality Traits of Duroc Breeding Stocks in Korea

  • Choi, J.S.;Jin, S.K.;Jeong, Y.H.;Jung, Y.C.;Jung, J.H.;Shim, K.S.;Choi, Y.I.
    • Asian-Australasian Journal of Animal Sciences
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    • v.29 no.9
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    • pp.1229-1238
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    • 2016
  • This study was conducted to determine the relationships of five intragenic single nucleotide polymorphism (SNP) markers (protein kinase adenosine monophosphate-activated ${\gamma}3$ subunit [PRKAG3], fatty acid synthase [FASN], calpastatin [CAST], high mobility group AT-hook 1 [HMGA1], and melanocortin-4 receptor [MC4R]) and meat quality traits of Duroc breeding stocks in Korea. A total of 200 purebred Duroc gilts from 8 sires and 40 dams at 4 pig breeding farms from 2010 to 2011 reaching market weight (110 kg) were slaughtered and their carcasses were chilled overnight. Longissimus dorsi muscles were removed from the carcass after 24 h of slaughter and used to determine pork properties including carcass weight, backfat thickness, moisture, intramuscular fat, $pH_{24h}$, shear force, redness, texture, and fatty acid composition. The PRKAG3, FASN, CAST, and MC4R gene SNPs were significantly associated with the meat quality traits (p<0.003). The meats of PRKAG3 (A 0.024/G 0.976) AA genotype had higher pH, redness and texture than those from PRKAG3 GG genotype. Meats of FASN (C 0.301/A 0.699) AA genotype had higher backfat thickness, texture, stearic acid, oleic acid and polyunsaturated fatty acid than FASN CC genotype. While the carcasses of CAST (A 0.373/G 0.627) AA genotype had thicker backfat, and lower shear force, palmitoleic acid and oleic acid content, they had higher stearic acid content than those from the CAST GG genotype. The MC4R (G 0.208/A 0.792) AA genotype were involved in increasing backfat thickness, carcass weight, moisture and saturated fatty acid content, and decreasing unsaturated fatty acid content in Duroc meat. These results indicated that the five SNP markers tested can be a help to select Duroc breed to improve carcass and meat quality properties in crossbred pigs.

${\beta}$-ketoacyl-acyl carrier protein synthases for fatty acid biosynthesis in bacteria

  • Lee, Hee-Jung;Youn, Youn-Ji;Ok, Jung-In;Lee, Jung-Won;Park, Hyo-Young;Cho, Kyung-Hae;Choi, Keum-Hwa
    • Proceedings of the PSK Conference
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    • 2002.10a
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    • pp.315.3-316
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    • 2002
  • A universal set of genes encodes the components of dissociated. type II. fa11y acid synthase system that is responsible for producing the multitude of fa11y acid structures found in bacterial membranes. We examined the biochemical basis for the production of fatty acids by bacteria. Several genes from HaemophHus influenzae Rd and three genes from Enterococcus faecalis V583 were predicted to encode homologs of the ${\beta}$-ketoacyl-acyl carrier protein synthases I or II or III of Escherichia coli(FabB or BabF, or FabH)were identified in the genomic database. The protein products were expressed. purified, and biochemically characterized. efFabH and hF abH carried out the initial condensation reaction of fatty acid biosynthesis with acetyl-Coenzyme A as a primer. and hFabB and efFabF1 carried out the elongation condensation reaction of fatty acid biosynthesis with myrixtoyl-ACP.

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Effect of Changes in the Composition of Cellular Fatty Acids on Membrane Fluidity of Rhodobacter sphaeroides

  • Kim, Eui-Jin;Lee, Jeong K.
    • Journal of Microbiology and Biotechnology
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    • v.25 no.2
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    • pp.162-173
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    • 2015
  • The cellular fatty acid composition is important for metabolic plasticity in Rhodobacter sphaeroides. We explored the effects of changing the cellular ratio of unsaturated fatty acids (UFAs) to saturated fatty acids (SFAs) in R. sphaeroides by overexpressing several key fatty acid biosynthetic enzymes through the use of expression plasmid pRK415. Bacteria containing the plasmid pRKfabI1 with the fabI1 gene that encodes enoyl-acyl carrier protein (ACP) reductase showed a reduction in the cellular UFA to SFA ratio from 4 (80% UFA) to 2 (65% UFA) and had decreased membrane fluidity and reduced cell growth. Additionally, the ratio of UFA to SFA of the chromatophore vesicles from pRKfabI1-containing cells was similarly lowered, and the cell had decreased levels of light-harvesting complexes, but no change in intracytoplasmic membrane (ICM) content or photosynthetic (PS) gene expression. Both inhibition of enoyl-ACP reductase with diazaborine and addition of exogenous UFA restored membrane fluidity, cell growth, and the UFA to SFA ratio to wild-type levels in this strain. R. sphaeroides containing the pRKfabB plasmid with the fabB gene that encodes the enzyme β-ketoacyl-ACP synthase I exhibited an increased UFA to SFA ratio from 4 (80% UFA) to 9 (90% UFA), but showed no change in membrane fluidity or growth rate relative to control cells. Thus, membrane fluidity in R. sphaeroides remains fairly unchanged when membrane UFA levels are between 80% and 90%, whereas membrane fluidity, cell growth, and cellular composition are affected when UFA levels are below 80%.