• Title/Summary/Keyword: ACSL1

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An Essential Role of the N-Terminal Region of ACSL1 in Linking Free Fatty Acids to Mitochondrial β-Oxidation in C2C12 Myotubes

  • Nan, Jinyan;Lee, Ji Seon;Lee, Seung-Ah;Lee, Dong-Sup;Park, Kyong Soo;Chung, Sung Soo
    • Molecules and Cells
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    • v.44 no.9
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    • pp.637-646
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    • 2021
  • Free fatty acids are converted to acyl-CoA by long-chain acyl-CoA synthetases (ACSLs) before entering into metabolic pathways for lipid biosynthesis or degradation. ACSL family members have highly conserved amino acid sequences except for their N-terminal regions. Several reports have shown that ACSL1, among the ACSLs, is located in mitochondria and mainly leads fatty acids to the β-oxidation pathway in various cell types. In this study, we investigated how ACSL1 was localized in mitochondria and whether ACSL1 overexpression affected fatty acid oxidation (FAO) rates in C2C12 myotubes. We generated an ACSL1 mutant in which the N-terminal 100 amino acids were deleted and compared its localization and function with those of the ACSL1 wild type. We found that ACSL1 adjoined the outer membrane of mitochondria through interaction of its N-terminal region with carnitine palmitoyltransferase-1b (CPT1b) in C2C12 myotubes. In addition, overexpressed ACSL1, but not the ACSL1 mutant, increased FAO, and ameliorated palmitate-induced insulin resistance in C2C12 myotubes. These results suggested that targeting of ACSL1 to mitochondria is essential in increasing FAO in myotubes, which can reduce insulin resistance in obesity and related metabolic disorders.

Glycolytic and oxidative muscles under acute glucose supplementation differ in their metabolic responses to fatty acyl-CoA synthetase gene suppression

  • Jung, Yun Hee;Bu, So Young
    • Journal of Nutrition and Health
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    • v.55 no.1
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    • pp.70-84
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    • 2022
  • Purpose: Skeletal muscles display significant heterogeneity in metabolic responses, owing to the composition of metabolically distinct fiber types. Recently, numerous studies have reported that in skeletal muscles, suppression of genes related to fatty acid channeling alters the triacylglycerol (TAG) synthesis and switches the energy substrates. However, such responses may differ, depending on the type of muscle fiber. Hence, we conducted in vitro and animal studies to compare the metabolic responses of different types of skeletal muscle fibers to the deficiency of fatty acyl-CoA synthetase (Acsl)6, one of the main fatty acid-activating enzymes. Methods: Differentiated skeletal myotubes were transfected with selected Acsl6 short interfering RNA (siRNA), and C57BL/6J mice were subjected to siRNA to induce Acsl6 deficiency. TAG accumulation and expression levels of insulin signaling proteins in response to acute glucose supplementation were measured in immortalized cell-based skeletal myotubes, oxidative muscles (OM), and glycolytic muscles (GM) derived from the animals. Results: Under conditions of high glucose supplementation, suppression of the Acsl6 gene resulted in decreased TAG and glycogen synthesis in the C2C12 skeletal myotubes. The expression of Glut4, a glucose transporter, was similarly downregulated. In the animal study, the level of TAG accumulation in OM was higher than levels determined in GM. However, a similar decrease in TAG accumulation was obtained in the two muscle types in response to Acsl6 suppression. Moreover, Acsl6 suppression enhanced the phosphorylation of insulin signaling proteins (Foxo-1, mTORc-1) only in GM, while no such changes were observed in OM. In addition, the induction ratio of phosphorylated proteins in response to glucose or Acsl6 suppression was significantly higher in GM than in OM. Conclusion: The results of this study demonstrate that Acsl6 differentially regulates the energy metabolism of skeletal muscles in response to glucose supplementation, thereby indicating that the fiber type or fiber composition of mixed muscles may skew the results of metabolic studies.

Regulation of Long-Chain Acyl-CoA Synthetase 4 Expression with Progesterone and Estradiol-$17{\beta}$ (프로게스테론과 에스트라디올 $17{\beta}$에 의한 Long-Chain Acyl-CoA Synthetase 4의 발현 조절)

  • Park, Hyo-Young;Kang, Man-Jong
    • Reproductive and Developmental Biology
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    • v.35 no.3
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    • pp.215-219
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    • 2011
  • Acyl-CoA synthetase 4(ACSL4) is an arachidonate-preferring enzyme abundant in steroidogenic tissues and postulated to modulate eicosanoid production. The human and mouse ACSL4 gene are mapped on chromosome X. The female mice heterozygous for ACSL4 deficiency became pregnant less frequent1y and produced small litters, with 40% of embryos surviving gestation. In this study, we examined the regulation of ACS4 by estradiol-$17{\beta}$ and progesterone (P4) in the human endometrial cancer cell line HTB-1B. ACSL4 mRNA was increased in a dose-dependent manner. Also, expression of ACSL4 gene was up-regulated in a time-dependent manner in HTB-1B cells. However, combined treatment with progesterone and estradiol-$17{\beta}$ modestly decreased the levels of ACS4L mRNA as compared with the estradiol-$17{\beta}$ and progesterone respectively. Overall, these results suggest that the ACSL4 gene is regulated by progesterone and estradiol-$17{\beta}$ in the HTB-1B cells.

A Study on the Vibration Analysis of Linear Stepping Motor using FEM and ACSL (유한요소법과 ACSL을 이용한 Linear Stepping Motor의 진동해석에 관한 연구)

  • 이상호;정도영
    • Journal of the Korean Institute of Illuminating and Electrical Installation Engineers
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    • v.18 no.1
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    • pp.122-128
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    • 2004
  • In this paper, the vibration characteristics of a linear stepping motor(LSM) are analyzed using the ACSL. A magnetic equivalent circuit is based on the structure of the LSM, and then the electric equivalent circuit of the LSM is derived by solving equations for the magnetic equivalent circuit. A normal force is calculated using finite element method(FEM). And the vibration characteristics(continuous vibration) of the LSM are simulated by the ACSL(Advanced Continuous Simulation language) with the voltage equations, the thrust equation, the normal force equation and the kinetic equation.

A Study on the Vibration Characteristics of 2-phase Linear Stepping Motor (2相 Linear Stepping Motor의 진동특성에 관한 연구)

  • 오홍석;김동희;이상호;정도영;김춘삼
    • The Transactions of the Korean Institute of Power Electronics
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    • v.4 no.6
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    • pp.554-560
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    • 1999
  • In this paper, a vibration suppression method using an energy stored in winding inductance and an induced v voltage of the Linear Stepping Motor(LSM) is shown, and it is applied to a new one-phase excitation method A And a magnetic equivalent circuit is based on the structure of the LSM, and then the electric equivalent circuit of the LSM is derived by solving equations for the magnetic equivalent circuit. Several dynamic characteristics of the LSM are analyzed by the ACSL with the voltage equations, the force equations and the kinetic equation, a and are measured by experimental system.

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Comparative analysis on genome-wide DNA methylation in longissimus dorsi muscle between Small Tailed Han and Dorper×Small Tailed Han crossbred sheep

  • Cao, Yang;Jin, Hai-Guo;Ma, Hui-Hai;Zhao, Zhi-Hui
    • Asian-Australasian Journal of Animal Sciences
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    • v.30 no.11
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    • pp.1529-1539
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    • 2017
  • Objective: The objective of this study was to compare the DNA methylation profile in the longissimus dorsi muscle between Small Tailed Han and Dorper${\times}$Small Tailed Han crossbred sheep which were known to exhibit significant difference in meat-production. Methods: Six samples (three in each group) were subjected to the methylated DNA immunoprecipitation sequencing (MeDIP-seq) and subsequent bioinformatics analyses to detect differentially methylated regions (DMRs) between the two groups. Results: 23.08 Gb clean data from six samples were generated and 808 DMRs were identified in gene body or their neighboring up/downstream regions. Compared with Small Tailed Han sheep, we observed a tendency toward a global loss of DNA methylation in these DMRs in the crossbred group. Gene ontology enrichment analysis found several gene sets which were hypomethylated in gene-body region, including nucleoside binding, motor activity, phospholipid binding and cell junction. Numerous genes were found to be differentially methylated between the two groups with several genes significantly differentially methylated, including transforming growth factor beta 3 (TGFB3), acyl-CoA synthetase long chain family member 1 (ACSL1), ryanodine receptor 1 (RYR1), acyl-CoA oxidase 2 (ACOX2), peroxisome proliferator activated receptor-gamma2 (PPARG2), netrin 1 (NTN1), ras and rab interactor 2 (RIN2), microtubule associated protein RP/EB family member 1 (MAPRE1), ADAM metallopeptidase with thrombospondin type 1 motif 2 (ADAMTS2), myomesin 1 (MYOM1), zinc finger, DHHC type containing 13 (ZDHHC13), and SH3 and PX domains 2B (SH3PXD2B). The real-time quantitative polymerase chain reaction validation showed that the 12 genes are differentially expressed between the two groups. Conclusion: In the current study, a tendency to a global loss of DNA methylation in these DMRs in the crossbred group was found. Twelve genes, TGFB3, ACSL1, RYR1, ACOX2, PPARG2, NTN1, RIN2, MAPRE1, ADAMTS2, MYOM1, ZDHHC13, and SH3PXD2B, were found to be differentially methylated between the two groups by gene ontology enrichment analysis. There are differences in the expression of 12 genes, of which ACSL1, RIN2, and ADAMTS2 have a negative correlation with methylation levels and the data suggest that DNA methylation levels in DMRs of the 3 genes may have an influence on the expression. These results will serve as a valuable resource for DNA methylation investigations on screening candidate genes which might be related to meat production in sheep.

Apolipoprotein H: a novel regulator of fat accumulation in duck myoblasts

  • Ziyi, Pan;Guoqing, Du;Guoyu, Li;Dongsheng, Wu;Xingyong, Chen;Zhaoyu, Geng
    • Journal of Animal Science and Technology
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    • v.64 no.6
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    • pp.1199-1214
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    • 2022
  • Apolipoprotein H (APOH) primarily engages in fat metabolism and inflammatory disease response. This study aimed to investigate the effects of APOH on fat synthesis in duck myoblasts (CS2s) by APOH overexpression and knockdown. CS2s overexpressing APOH showed enhanced triglyceride (TG) and cholesterol (CHOL) contents and elevated the mRNA and protein expression of AKT serine/threonine kinase 1 (AKT1), ELOVL fatty acid elongase 6 (ELOVL6), and acetyl-CoA carboxylase 1 (ACC1) while reducing the expression of protein kinase AMP-activated catalytic subunit alpha 1 (AMPK), peroxisome proliferator activated receptor gamma (PPARG), acyl-CoA synthetase long chain family member 1 (ACSL1), and lipoprotein lipase (LPL). The results showed that knockdown of APOH in CS2s reduced the content of TG and CHOL, reduced the expression of ACC1, ELOVL6, and AKT1, and increased the gene and protein expression of PPARG, LPL, ACSL1, and AMPK. Our results showed that APOH affected lipid deposition in myoblasts by inhibiting fatty acid beta-oxidation and promoting fatty acid biosynthesis by regulating the expression of the AKT/AMPK pathway. This study provides the necessary basic information for the role of APOH in fat accumulation in duck myoblasts for the first time and enables researchers to study the genes related to fat deposition in meat ducks in a new direction.

Korean pine nut oil replacement decreases intestinal lipid uptake while improves hepatic lipid metabolism in mice

  • Zhu, Shuang;Park, Soyoung;Lim, Yeseo;Shin, Sunhye;Han, Sung Nim
    • Nutrition Research and Practice
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    • v.10 no.5
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    • pp.477-486
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    • 2016
  • BACKGROUND/OBJECTIVES: Consumption of pine nut oil (PNO) was shown to reduce weight gain and attenuate hepatic steatosis in mice fed a high-fat diet (HFD). The aim of this study was to examine the effects of PNO on both intestinal and hepatic lipid metabolism in mice fed control or HFD. MATERIALS/METHODS: Five-week-old C57BL/6 mice were fed control diets containing 10% energy fat from either Soybean Oil (SBO) or PNO, or HFD containing 15% energy fat from lard and 30% energy fat from SBO or PNO for 12 weeks. Expression of genes related to intestinal fatty acid (FA) uptake and channeling (Cd36, Fatp4, Acsl5, Acbp), intestinal chylomicron synthesis (Mtp, ApoB48, ApoA4), hepatic lipid uptake and channeling (Lrp1, Fatp5, Acsl1, Acbp), hepatic triacylglycerol (TAG) lipolysis and FA oxidation (Atgl, Cpt1a, Acadl, Ehhadh, Acaa1), as well as very low-density lipoprotein (VLDL) assembly (ApoB100) were determined by real-time PCR. RESULTS: In intestine, significantly lower Cd36 mRNA expression (P<0.05) and a tendency of lower ApoA4 mRNA levels (P = 0.07) was observed in PNO-fed mice, indicating that PNO consumption may decrease intestinal FA uptake and chylomicron assembly. PNO consumption tended to result in higher hepatic mRNA levels of Atgl (P = 0.08) and Cpt1a (P = 0.05). Significantly higher hepatic mRNA levels of Acadl and ApoB100 were detected in mice fed PNO diet (P<0.05). These results suggest that PNO could increase hepatic TAG metabolism; mitochondrial fatty acid oxidation and VLDL assembly. CONCLUSIONS: PNO replacement in the diet might function in prevention of excessive lipid uptake by intestine and improve hepatic lipid metabolism in both control diet and HFD fed mice.

A Voltage Disturbance Detection Method for Computer Application Lods (컴퓨터 응용 부하들을 위한 전압 외란 검출 방법)

  • 이상훈;최재호
    • The Transactions of the Korean Institute of Power Electronics
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    • v.5 no.6
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    • pp.584-591
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    • 2000
  • Power Quality Compensator(PQC) has been installed to protect the sensitive loads against the voltage disturbances, such as voltage sag and interruption. In general, static switch is used for the purpose of link between utility and PQC. So transfer operation of the static switch play a important part in the PQC. Many studies on the structure and control of PQC have been progressed in active, but these researches have been rarely mentioned about any voltage-disturbances-detection method to start the PQC operation. In this paper, a new voltage-disturbances-detection algorithm for computer application loads using the CBEMA/ITIC curve is proposed for transfer operation of the static switch. The proposed detection algorithm is implemented to get fast detecting time through the comparison of instantaneous 3-phase voltage values transferred to DC values in the synchronous reference frame with the operating reference values. To get the robust characteristics against the noise, a first order digital filter is designed. The magnitude falling and phase delay caused by the filter are compensated through the error normalizing and numerical analysis using transfer function, respectively. Finally, the validity of the proposed algorithm is proved by ACSL simulation and experimental results.

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Design of IM Control System for Industrial Sewing Ma-chines

  • Hwang, Dae-kyu;Oh, Tae-Seok;Kim, Il-Hwan
    • 제어로봇시스템학회:학술대회논문집
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    • 2002.10a
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    • pp.91.3-91
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    • 2002
  • This paper describes a design of an induction motor control system for industrial sewing machines. On the basis of vector control principle, the control system is simulated by using the ACSL, implemented on a DSP(TMS320C31).A space vector modulation is used as the inverter switching strategy. For the application of industrial sewing machines, A fast acceleration (deceleration) and removal of velocity ripples are required, because a sewing quality and sewing machines life time depends on these characteristics. The designed control system has fast dynamic characteristics and small speed vibration. The result is applied to the industrial sewing machine and result are shown.

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