• Journal of Microbiology and Biotechnology
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• v.28 no.4
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• pp.597-605
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• 2018

Acyl-CoA oxidases (ACOXs) play important roles in lipid metabolism, including peroxisomal fatty acid ${\beta}$-oxidation by the conversion of acyl-CoAs to 2-trans-enoyl-CoAs. The yeast Yarrowia lipolytica can utilize fatty acids as a carbon source and thus has extensive biotechnological applications. The crystal structure of ACOX3 from Y. lipolytica (YlACOX3) was determined at a resolution of $2.5{\AA}$. It contained two molecules per asymmetric unit, and the monomeric structure was folded into four domains; $N{\alpha}$, $N{\beta}$, $C{\alpha}1$, and $C{\alpha}2$ domains. The cofactor flavin adenine dinucleotide was bound in the dimer interface. The substrate-binding pocket was located near the cofactor, and formed at the interface between the $N{\alpha}$, $N{\beta}$, and $C{\alpha}1$ domains. Comparisons with other ACOX structures provided structural insights into how YlACOX has a substrate preference for short-chain acyl-CoA. In addition, the structure of YlACOX3 was compared with those of medium- and long-chain ACOXs, and the structural basis for their differences in substrate specificity was discussed.

• Proceedings of the Botanical Society of Korea Conference
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• 1999.07a
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• pp.37-40
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• 1999

cDNAs for long- and short-chain acyl-CoA oxidases in fatty acid $\beta$-oxidation were isolated and were characterized their enzymatical and molecular properties. Both oxidases were exclusively localized in glyoxysomes, indicating that glyoxysomes can completely metabolize fatty acids to acyl-CoA by their cooperative action. In order to clarify the regulatory mechanisms underlying degradation of storage oil, we tried to obtain glyoxysome-deficient mutants of Arabidopsis. We screened 2,4-dichlorophenoxybutyric acid (2,4-DB) mutants of Arabidopsis which have defects in glyoxysomal fatty acid $\beta$-oxidation. Four mutants can be classified as carrying alleles at three independent loci, which we designated pedl, ped2, and ped3, respectively (where ped stands for peroxisome defective). The characteristics of these ped mutants are described.

• Biomedical Science Letters
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• v.16 no.4
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• pp.239-246
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• 2010

It is suggested that ovariectomy induces body weight gain primarily in the form of adipose tissue in rodents. Since liver peroxisome proliferator-activated receptor ${\alpha}$ (PPAR${\alpha}$) and uncoupling 2 (UCP2) are involved in the regulation of energy expenditure, it was investigated whether swim training regulates ovariectomy-induced adiposity and steatosis through liver PPAR${\alpha}$ and UCP2 activation in female ovariectomized mice, an animal model of postmenopausal women. Swim-trained mice had significantly decreased adipose tissue weights compared with sedentary control mice. Histological analysis showed that hepatic lipid accumulation was inhibited by swim training. Concomitantly, swim training significantly increased mRNA levels of PPAR${\alpha}$ and its target genes responsible for peroxisomal fatty acid ${\beta}$-oxidation, such as acyl-CoA oxidase, enoyl-CoA hydratase/3-hydroxyacyl-CoA dehydrogenase and thiolase in the liver. Moreover, swim training induced the mRNA expression of UCP2. These results suggest that swim training can effectively prevent adiposity and steatosis caused by ovariectomy, in part through activation of liver PPAR${\alpha}$ and UCP2 in female obese mice.

• Nutrition Research and Practice
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• v.7 no.3
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• pp.153-159
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• 2013

We investigated whether the combination of phytochemicals and acetic acid in the form of fruit vinegar provides an additive effect on changes of mRNA levels related to fatty acid oxidation in human hepatocyte (HepG2). Among the seven fruit vinegars (Rubuscoreanus, Opuntia, blueberry, cherry, red ginseng, mulberry, and pomegranate) studied, treatment of HepG2 with pomegranate vinegar (PV) at concentrations containing 1 mM acetic acid showed the highest in vitro potentiating effect on the mRNA expression levels of peroxisome proliferator-activated receptor ${\alpha}$, carnitinepalmitoyl transferase-1, and acyl-CoA oxidase compared to the control group (P < 0.05). Reversed-phase liquid chromatography in combination with quadrupole time-of-flight mass spectrometry analysis revealed four potential compounds (punicalagin B, ellagic acid, and two unidentified compounds) responsible for altered gene expression in HepG2 cells treated with PV as compared with the others. Further investigations are warranted to determine if drinking PV beverages may help to maintain a healthy body weight in overweight subjects.

• 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.

• Asian-Australasian Journal of Animal Sciences
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• v.28 no.8
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• pp.1075-1083
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• 2015

Adipose tissue deposited within muscle fibers, known as intramuscular fat (IMF or marbling), is a major determinant of meat quality and thereby affects its economic value. The biological mechanisms that determine IMF content are therefore of interest. In this study, 48 genes involved in the bovine peroxisome proliferator-activated receptor signaling pathway, which is involved in lipid metabolism, were investigated to identify candidate genes associated with IMF in the longissimus dorsi of Hanwoo (Korean cattle). Ten genes, retinoid X receptor alpha, peroxisome proliferator-activated receptor gamma (PPARG), phospholipid transfer protein, stearoyl-CoA desaturase, nuclear receptor subfamily 1 group H member 3, fatty acid binding protein 3 (FABP3), carnitine palmitoyltransferase II, acyl-Coenzyme A dehydrogenase long chain (ACADL), acyl-Coenzyme A oxidase 2 branched chain, and fatty acid binding protein 4, showed significant effects with regard to IMF and were differentially expressed between the low- and high-marbled groups (p<0.05). Analysis of the gene co-expression network based on Pearson's correlation coefficients identified 10 up-regulated genes in the high-marbled group that formed a major cluster. Among these genes, the PPARG-FABP4 gene pair exhibited the strongest correlation in the network. Glycerol kinase was found to play a role in mediating activation of the differentially expressed genes. We categorized the 10 significantly differentially expressed genes into the corresponding downstream pathways and investigated the direct interactive relationships among these genes. We suggest that fatty acid oxidation is the major downstream pathway affecting IMF content. The PPARG/RXRA complex triggers activation of target genes involved in fatty acid oxidation resulting in increased triglyceride formation by ATP production. Our findings highlight candidate genes associated with the IMF content of the loin muscle of Korean cattle and provide insight into the biological mechanisms that determine adipose deposition within muscle.

• Journal of Physiology & Pathology in Korean Medicine
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• v.28 no.3
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• pp.288-295
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• 2014

Bojungchiseub-tang (BJCST) has been used in symptoms and signs of edema, dampness-phlegm, kidney failure, and so on. BJCST is also expected to have strong anti-obesity activities. However, little is known about the mechanisms of its inhibitory effects on adipocyte differentiation and adipogenesis. In the present study, we examined the effects and mechanism of BJCST on transcription factors and adipogenic genes of 3T3-L1 preadipocytes to understand its inhibitory effects on adipocyte differentiation and adipogenesis. Our results showed that BJCST significantly inhibited differentiation and adipogenesis of 3T3-L1 preadipocytes in a dose-dependent manner. To elucidate the mechanism of the effects of BJCST on lowering lipid content in 3T3-L1 adipocytes, we examined whether BJCST modulate the expressions of transcription factors to induce adipogenesis and adipogenic genes related to regulate accumulation of lipids. As a result, the expression of steroid regulatory element-binding protein (SREBP)1, cytidine-cytidine-adenosine-adenosine-thymidine (CCAAT)/enhancer binding proteins ${\alpha}$ ($C/EBP{\alpha}$), $C/EBP{\beta}$, $C/EBP{\delta}$, and peroxisome proliferator-activated receptor ${\gamma}$ ($PPAR{\gamma}$) genes, which induce the adipose differentiation, liver X receptor $(LXR){\alpha}$ and fatty acid synthase (FAS) genes, which induce lipogenesis and adipose-specific aP2, Adipsin, lipoprotein lipase (LPL), CD36, TGF-${\beta}$, leptin and adiponectin genes, which compose fat formation were decreased. BJCST also reduced the expression of acyl CoA oxidase (ACO) and uncoupling protein (UCP) genes related to lipid oxidation. In conclusion, BJCST could regulate transcript factor related to induction of adipose differentiation and inhibited the accumulation of lipids and expression of adipogenic genes.

• Korean Journal of Food Science and Technology
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• v.48 no.4
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• pp.384-391
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• 2016

In previous studies, we confirmed that the ethanol extract of Polygonatum sibiricum (ID1216) has anti-obesity effects on high-fat diet-fed mice. To identify the obesity-related genes affected by ID1216, we studied its effects both in vivo and in vitro. In mice, single administration of ID1216 increased the expression of obesity-related genes including sirtuin1 (SIRT1), peroxisome proliferator-activated receptor ${\gamma}$ coactivator $1{\alpha}$ ($PGC1{\alpha}$) and peroxisome proliferator-activated receptor ${\alpha}$ ($PPAR{\alpha}$) compared to that in mice administered the vehicle; their downstream genes (uncoupling proteins, acyl-CoA oxidase, adipocyte protein 2, and hormone-sensitive lipase) were also increased by ID1216. In fully differentiated 3T3-L1 adipocytes, ID1216 showed the same effects on anti-obesity genes as those in the animal model. Based on these results, we propose that ID1216 has anti-obesity effects by regulating the $SIRT1-PGC1{\alpha}-PPAR{\alpha}$ pathway and their downstream genes, thereby controlling energy and lipid metabolisms.

• BMB Reports
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• v.52 no.9
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• pp.566-571
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• 2019

Lymphoma is one of the most curable types of cancer. However, drug resistance is the main challenge faced in lymphoma treatment. Peroxisomal acyl-CoA oxidase 1 (ACOX1) is the rate-limiting enzyme in fatty acid ${\beta}$-oxidation. Deregulation of ACOX1 has been linked to peroxisomal disorders and carcinogenesis in the liver. Currently, there is no information about the function of ACOX1 in lymphoma. In this study, we found that upregulation of ACOX1 promoted proliferation in lymphoma cells, while downregulation of ACOX1 inhibited proliferation and induced apoptosis. Additionally, overexpression of ACOX1 increased resistance to doxorubicin, while suppression of ACOX1 expression markedly potentiated doxorubicin-induced apoptosis. Interestingly, downregulation of ACOX1 promoted mitochondrial location of Bad, reduced mitochondrial membrane potential and provoked apoptosis by activating caspase-9 and caspase-3 related apoptotic pathway. Overexpression of ACOX1 alleviated doxorubicin-induced activation of caspase-9 and caspase-3 and decrease of mitochondrial membrane potential. Importantly, downregulation of ACOX1 increased p73, but not p53, expression. p73 expression was critical for apoptosis induction induced by ACOX1 downregulation. Also, overexpression of ACOX1 significantly reduced stability of p73 protein thereby reducing p73 expression. Thus, our study indicated that suppression of ACOX1 could be a novel and effective approach for treatment of lymphoma.

• Journal of Oriental Neuropsychiatry
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• v.20 no.1
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• pp.147-164
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• 2009

Objectives : We investigated the effects of Sopungsungi-won(Shu!engshunqiyuan) (SSEx1, SSEx2) to treat the metabolic syndrome by the molecular mechanism of regulation of PPAR and modulation of mitochondrial MCAD, VLCAD mRNA expression. Methods : Mouse NMu2Li liver cells and C2C12 skeletal muscle myogenic progenital cells were transiently transfected with expression plasmids for PPAR(PPAR${\alpha}$, PPAR${\delta}$), a luciferase reporter gene construct containing 3 copies of the PPRE from the rat acyl-CoA oxidase gene and ${\beta}$-galactosidase gene. Cells were treated with several concentrated kinds of SSEx1, SSEx2 at the initial time of culture and analyzed PPAR${\alpha}$, PPAR${\delta}$ reporter gene activity using spectrophotometer (405 nm). Total RNA was extracted from SSEx1, SSEx2 and measured mRNA levels of mitochondrial MCAD, VLCAD. Representative RT-PCR bands are shown. Results : 1. SSEx1 increased the expression of PPAR${\alpha}$ reporter gene activities at 0.1 ${\mu}$g/ml (p${\mu}$g/ml (p<0.05), SSEx2 at 0.1 ${\mu}$g/ml (p${\mu}$g/ml (p<0.05) significantly in NMu2Li liver cell lines. 2. SSEx1 increased the expression of PPAR${\alpha}$ reporter gene activities at 1 ${\mu}$g/ml (p${\mu}$g/ml (p${\alpha}$ reporter gene activities in C2C12 skeletal muscle cells. 4. SSEx1 increased the modulation of mitochondrial MCAD mRNA expression (p<0.05) significantly in NMu2Li liver cell lines. 5. SSEx1, SSEx2 both increased the modulation of mitochondrial MCAD mRNA expression (p<0.05) significantly in C2C12 skeletal muscle cells. Conclusions : These results show the SSEx1, SSEx2 can be used as therapeutic agent for metabolic syndrome and it's molecular mechanisms of PPAR more contribute to the activation of PPAR${\alpha}$ then PPAR${\delta}$ reporter gene activities and it's total RNA more contribute to the modulation of mitochondrial MCAD then VLCAD mRNA expression.