Yong Sung Lee

Hanyang University, Sŏul, Seoul, South Korea

Are you Yong Sung Lee?

Claim your profile

Publications (28)73.31 Total impact

  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Doublesex and Mab-3-related transcription factor (Dmrt) gene family members have rarely been identified or characterized in aquatic invertebrates. In this study, we identified and characterized three DM domain-containing genes - Dmrt11E, Dmrt93B, and Dmrt99B - in the monogonont rotifer, Brachionus koreanus. DM domains of the proteins encoded by the B. koreanus Dmrt (Bk-Dmrt) genes had high similarities to DM domains of other invertebrate species. To understand the potential effects of environmental stressors on the transcriptional expression of Dmrt genes in rotifers, we exposed B. koreanus to a wide range of UV-B radiation and different concentrations of benzo[a]pyrene (B[a]P) over different time courses. Transcript levels of all Bk-Dmrt genes decreased significantly in response to relatively high doses of UV-B irradiation, and were also downregulated in response to exposure to UV-B radiation over time. Transcript levels of all Bk-Dmrt genes were downregulated in response to B[a]P exposure for 24 h. This decrease in expression of all Bk-Dmrt genes was concomitant with the growth retardation induced by UV-B and B[a]P exposure. We concluded that both environmental stressors have detrimental effects on transcriptional regulation of all Bk-Dmrt genes, especially relatively high doses of these stressors, leading to growth retardation. However, further studies are required to better understand the potential role of Dmrt genes in environmental stressor-triggered growth retardation in the rotifer B. koreanus.
    Comparative Biochemistry and Physiology Part B Biochemistry and Molecular Biology 08/2014; 174B(36):44. · 2.07 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: In this study, we investigated the effects of the water-accommodated fraction (WAF) of crude oil on the development and reproduction of the intertidal copepod Tigriopus japonicus through life-cycle experiments. Furthermore, we investigated the mechanisms underlying the toxic effects of WAF on this benthic organism by studying expression patterns of cytochrome P450 (CYP) genes. Development of T. japonicus was delayed and molting was interrupted in response to WAF exposure. Hatching rate was also significantly reduced in response to WAF exposure. Activities of antioxidant enzymes such as glutathione S-transferase (GST), glutathione reductase (GR), and catalase (CAT) were increased by WAF exposure in a concentration-dependent manner. These results indicated that WAF exposure resulted in oxidative stress, which in turn was associated with dysfunctional development and reproduction. To evaluate the involvement of cytochrome P450 (CYP) genes, we cloned the entire repertoire of CYP genes in T. japonicus (n = 52) and found that the CYP genes belonged to five different clans (i.e., Clans 2, 3, 4, mitochondrial, and 20). We then examined expression patterns of these 52 CYP genes in response to WAF exposure. Three TJ-CYP genes (CYP3024A2, CYP3024A3, and CYP3027C2) belonging to CYP clan 3 were significantly induced by WAF exposure in a time- and concentration-dependent manner. We identified aryl hydrocarbon responsive elements (AhRE), xenobiotic responsive elements (XREs), and metal response elements (MRE) in the promoter regions of these three CYP genes, suggesting that these genes are involved in detoxification of toxicants. Overall, our results indicate that WAF can trigger oxidative stress and thus induce dysfunctional development and reproduction in the copepod T. japonicus. Furthermore, we identified three TJ-CYP genes that represent potential biomarkers of oil pollution.
    Aquatic Toxicology 08/2014; 152:308-317. · 3.51 Impact Factor
  • Source
    Aquatic Toxicology 07/2014; · 3.51 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Kim, B.-M., J.-S. Rhee, C.-B. Jeong, S.-J. Lee, Y.S. Lee, I.-Y. Choi, and J.-S. Lee,
    Aquatic Toxicology 07/2014; · 3.51 Impact Factor
  • Aquatic Toxicology 06/2014; · 3.51 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: In this study, we investigated the effects of the water-accommodated fraction (WAF) of crude oil on the development and reproduction of the intertidal copepod Tigriopus japonicus through life-cycle experiments. Furthermore, we investigated the mechanisms underlying the toxic effects of WAF on this benthic organism by studying expression patterns of cytochrome P450 (CYP) genes. Development of T. japonicus was delayed and molting was interrupted in response to WAF exposure. Hatching rate was also significantly reduced in response to WAF exposure. Activities of antioxidant enzymes such as glutathione S-transferase (GST), glutathione reductase (GR), and catalase (CAT) were increased by WAF exposure in a concentration-dependent manner. These results indicated that WAF exposure resulted in oxidative stress, which in turn was associated with dysfunctional development and reproduction. To evaluate the involvement of cytochrome P450 (CYP) genes, we cloned the entire repertoire of CYP genes in T. japonicus (n=52) and found that the CYP genes belonged to five different clans (i.e., Clans 2, 3, 4, mitochondrial, and 20). We then examined expression patterns of these 52 CYP genes in response to WAF exposure. Three TJ-CYP genes (CYP3024A2, CYP3024A3, and CYP3027C2) belonging to CYP clan 3 were significantly induced by WAF exposure in a time- and concentration-dependent manner. We identified aryl hydrocarbon responsive elements (AhRE), xenobiotic responsive elements (XREs), and metal response elements (MRE) in the promoter regions of these three CYP genes, suggesting that these genes are involved in detoxification of toxicants. Overall, our results indicate that WAF can trigger oxidative stress and thus induce dysfunctional development and reproduction in the copepod T. japonicus. Furthermore, we identified three TJ-CYP genes that represent potential biomarkers of oil pollution.
    Aquatic toxicology (Amsterdam, Netherlands) 05/2014; 152C:308-317. · 3.12 Impact Factor
  • Source
    Comparative Biochemistry and Physiology Part C Toxicology & Pharmacology 05/2014; · 2.71 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Nuclear radioisotope accidents are potentially ecologically devastating due to their impact on marine organisms. To examine the effects of exposure of a marine organism to radioisotopes, we irradiated the intertidal copepod Tigriopus japonicus with several doses of gamma radiation and analyzed the effects on mortality, fecundity, and molting by assessing antioxidant enzyme activities and gene expression patterns. No mortality was observed at 96h, even in response to exposure to a high dose (800Gy) of radiation, but mortality rate was significantly increased 120h (5 days) after exposure to 600 or 800Gy gamma ray radiation. We observed a dose-dependent reduction in fecundity of ovigerous females; even the group irradiated with 50Gy showed a significant reduction in fecundity, suggesting that gamma rays are likely to have a population level effect. In addition, we observed growth retardation, particularly at the nauplius stage, in individuals after gamma irradiation. In fact, nauplii irradiated with more than 200Gy, though able to molt to copepodite stage 1, did not develop into adults. Upon gamma radiation, T. japonicus showed a dose-dependent increase in reactive oxygen species (ROS) levels, the activities of several antioxidant enzymes, and expression of double-stranded DNA break damage genes (e.g. DNA-PK, Ku70, Ku80). At a low level (sub-lethal dose) of gamma irradiation, we found dose-dependent upregulation of p53, implying cellular damage in T. japonicus in response to sub-lethal doses of gamma irradiation, suggesting that T. japonicus is not susceptible to sub-lethal doses of gamma irradiation. Additionally, antioxidant genes, phase II enzyme (e.g. GSTs), and cellular chaperone genes (e.g. Hsps) that are involved in cellular defense mechanisms also showed the same expression patterns for sublethal doses of gamma irradiation (50-200Gy). These findings indicate that sublethal doses of gamma radiation can induce oxidative stress-mediated DNA damage and increase the expression of antioxidant enzymes and proteins with chaperone-related functions, thereby significantly affecting life history parameters such as fecundity and molting in the copepod T. japonicus.
    Aquatic toxicology (Amsterdam, Netherlands) 04/2014; 152C:264-272. · 3.12 Impact Factor
  • Aquatic Toxicology 04/2014; · 3.51 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Despite being a strong toxicant for aquatic ecosystems, the effect of benzo[a]pyrene (B[a]P) on whole cytochrome P450 (CYP) biotransformation mechanisms has not been deeply investigated in aquatic organisms. To understand the mode of action of B[a]P on CYP molecular responses in fish, we analyzed the full spectrum of cyp genes and the activities of enzymes that are involved in detoxification and antioxidant defense systems after exposure to different concentrations of B[a]P over different time courses in the marine medaka, Oryzias melastigma. Upon B[a]P exposure, we found significant downregulation of cyp genes associated with steroidogenesis with decreased concentrations of actual hormones including estradiol (E2) and testosterone (11-KT), indicating that B[a]P-treated groups were closely associated with the dysfunction of hormone synthesis in a dose-dependent manner. In addition, B[a]P exposure strongly influenced transcriptional levels of antioxidant-related genes and their enzyme activities. Based on these results, we suggest that B[a]P induced the CYPs-involved systematic biotransformation mechanism with oxidative stress in the juvenile marine medaka, resulting in changes of endogenous hormonal levels and transcriptional levels of several steroidogenic metabolism-related CYPs.
    Aquatic toxicology (Amsterdam, Netherlands) 04/2014; 152C:232-243. · 3.12 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: To investigate effect of endocrine disrupting chemicals (EDCs) on the circadian rhythm pathway, we cloned clock and circadian rhythmic pathway-associated genes (e.g. Per2, Cry1, Cry2, and BMAL1) in the self-fertilizing mangrove killifish Kryptolebias marmoratus. Initially, we obtained 2,223 bp (741 aa) of open reading frame (ORF) for the K. marmoratus clock gene (Km-clock). The gene consisted of 5,791 bp of genomic DNA spanning 17 exons. In order to perform an integrated analysis of the circadian rhythmic pathway, we also cloned the BMAL1, Cry1, Cry2, and Per2 genes from K. marmoratus and registered these sequences in GenBank. The promoter region of Km-clock had 1 aryl hydrocarbon receptor element (AhRE, GTGCGTGACA) and 8 estrogen receptor (ER) half-sites, indicating that the AhRE and ER half sites would likely be associated with regulation of clock protein activity during EDCs-induced cellular stress. The Km-clock protein domains (bHLH, PAS1, PAS2) were highly conserved in five additional fish species (zebrafish, Japanese medaka, Southern platyfish, Nile tilapia, and spotted green pufferfish), suggesting that the fish clock protein may play an important role in controlling endogenous circadian rhythms. The promoter regions of Km-BMAL1, -Cry1, -Cry2, and -Per2 were found to contain several xenobiotic response elements (XREs), indicating that EDCs may be able to alter the expression of these genes. To analyze the endogenous circadian rhythm in K. marmoratus, we measured expression of Km-clock and other circadian rhythmic genes (e.g. Per2, Cry1, Cry2, and BMAL1) in different tissues, and found ubiquitous expression, although there were different patterns of transcript amplification during different developmental stages. In an estrogen (E2)-exposed group, Km-clock expression was down-regulated, however, a hydroxytamoxifen (TMX, nonsteroid estrogen antagonist)-exposed group showed an upregulated pattern of Km-clock expression, suggesting that expression of Km-clock is closely associated with exposure to EDCs. In response to exposure to bisphenol A (BPA) and 4-tert-octyphenol (OP), Km-clock expression was down-regulated in pituitary/brain, muscle, and skin in both gender types (hermaphrodite and secondary male). In juvenile K. marmoratus liver tissue, expression of Km-clock and other circadian rhythmic pathway-associated genes showed a regular oscillation pattern over a period of approximately 24 hours during a 12L:12D cycle. However, the circadian rhythm of BPA-exposed juvenile K. marmoratus liver tissue was perturbed over a 12L:12D period. This study will aid in our understanding of how EDCs perturb endogenous circadian rhythms, particularly in BPA-exposed fish liver tissue.
    Comparative Biochemistry and Physiology Part C Toxicology & Pharmacology 04/2014; · 2.71 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: To investigate the effect of endocrine disrupting chemicals (EDCs) on the circadian rhythm pathway, we cloned clock and circadian rhythmic pathway-associated genes (e.g. Per2, Cry1, Cry2, and BMAL1) in the self-fertilizing mangrove killifish Kryptolebias marmoratus. Initially, we obtained 2223 bp (741 aa) of open reading frame (ORF) for the K. marmoratus clock gene (Km-clock). The gene consisted of 5791 bp of genomic DNA spanning 17 exons. In order to perform an integrated analysis of the circadian rhythmic pathway, we also cloned the BMAL1, Cry1, Cry2, and Per2 genes from K. marmoratus and registered these sequences in GenBank. The promoter region of Km-clock had 1 aryl hydrocarbon receptor element (AhRE, GTGCGTGACA) and 8 estrogen receptor (ER) half-sites, indicating that the AhRE and ER half sites would likely be associated with regulation of clock protein activity during EDCs-induced cellular stress. The Km-clock protein domains (bHLH, PAS1, PAS2) were highly conserved in five additional fish species (zebrafish, Japanese medaka, Southern platyfish, Nile tilapia, and spotted green pufferfish), suggesting that the fish clock protein may play an important role in controlling endogenous circadian rhythms. The promoter regions of Km-BMAL1, -Cry1, -Cry2, and -Per2 were found to contain several xenobiotic response elements (XREs), indicating that EDCs may be able to alter the expression of these genes. To analyze the endogenous circadian rhythm in K. marmoratus, we measured expression of Km-clock and other circadian rhythmic genes (e.g. Per2, Cry1, Cry2, and BMAL1) in different tissues, and found ubiquitous expression, although there were different patterns of transcript amplification during different developmental stages. In an estrogen (E2)-exposed group, Km-clock expression was down-regulated, however, a hydroxytamoxifen (TMX, nonsteroid estrogen antagonist)-exposed group showed an upregulated pattern of Km-clock expression, suggesting that the expression of Km-clock is closely associated with exposure to EDCs. In response to the exposure of bisphenol A (BPA) and 4-tert-octyphenol (OP), Km-clock expression was down-regulated in the pituitary/brain, muscle, and skin in both gender types (hermaphrodite and secondary male). In juvenile K. marmoratus liver tissue, expression of Km-clock and other circadian rhythmic pathway-associated genes showed a regular oscillation pattern over a period of approximately 24 h during a 12L:12D cycle. However, the circadian rhythm of BPA-exposed juvenile K. marmoratus liver tissue was perturbed over a 12L:12D period. This study will aid in our understanding of how EDCs perturb endogenous circadian rhythms, particularly in BPA-exposed fish liver tissue.
    Comparative Biochemistry and Physiology Part C Toxicology & Pharmacology 04/2014; · 2.71 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Nuclear radioisotope accidents are potentially ecologically devastating due to their impact on marine organisms. To examine the effects of exposure of a marine organism to radioisotopes, we irradiated the intertidal copepod Tigriopus japonicus with several doses of gamma radiation and analyzed the effects on mortality, fecundity, and molting by assessing antioxidant enzyme activities and gene expression patterns. No mortality was observed at 96 h, even in response to exposure to a high dose (800 Gy) of radiation, but mortality rate was significantly increased 120 h (5 days) after exposure to 600 or 800 Gy gamma ray radiation. We observed a dose-dependent reduction in fecundity of ovigerous females; even the group irradiated with 50 Gy showed a significant reduction in fecundity, suggesting that gamma rays are likely to have a population level effect. In addition, we observed growth retardation, particularly at the nauplius stage, in individuals after gamma irradiation. In fact, nauplii irradiated with more than 200 Gy, though able to molt to copepodite stage 1, did not develop into adults. Upon gamma radiation, T. japonicus showed a dose-dependent increase in reactive oxygen species (ROS) levels, the activities of several antioxidant enzymes, and expression of double-stranded DNA break damage genes (e.g. DNA-PK, Ku70, Ku80). At a low level (sub-lethal dose) of gamma irradiation, we found dose-dependent upregulation of p53, implying cellular damage in T. japonicus in response to sub-lethal doses of gamma irradiation, suggesting that T. japonicus is not susceptible to sub-lethal doses of gamma irradiation. Additionally, antioxidant genes, phase II enzyme (e.g. GSTs), and cellular chaperone genes (e.g. Hsps) that are involved in cellular defense mechanisms also showed the same expression patterns for sublethal doses of gamma irradiation (50–200 Gy). These findings indicate that sublethal doses of gamma radiation can induce oxidative stress-mediated DNA damage and increase the expression of antioxidant enzymes and proteins with chaperone-related functions, thereby significantly affecting life history parameters such as fecundity and molting in the copepod T. japonicus.
    Aquatic Toxicology. 01/2014; 152:264–272.
  • [Show abstract] [Hide abstract]
    ABSTRACT: Despite being a strong toxicant for aquatic ecosystems, the effect of benzo[a]pyrene (B[a]P) on whole cytochrome P450 (CYP) biotransformation mechanisms has not been deeply investigated in aquatic organisms. To understand the mode of action of B[a]P on CYP molecular responses in fish, we analyzed the full spectrum of cyp genes and the activities of enzymes that are involved in detoxification and antioxidant defense systems after exposure to different concentrations of B[a]P over different time courses in the marine medaka, Oryzias melastigma. Upon B[a]P exposure, we found significant downregulation of cyp genes associated with steroidogenesis with decreased concentrations of actual hormones including estradiol (E2) and testosterone (11-KT), indicating that B[a]P-treated groups were closely associated with the dysfunction of hormone synthesis in a dose-dependent manner. In addition, B[a]P exposure strongly influenced transcriptional levels of antioxidant-related genes and their enzyme activities. Based on these results, we suggest that B[a]P induced the CYPs-involved systematic biotransformation mechanism with oxidative stress in the juvenile marine medaka, resulting in changes of endogenous hormonal levels and transcriptional levels of several steroidogenic metabolism-related CYPs.
    Aquatic Toxicology. 01/2014; 152:232–243.
  • [Show abstract] [Hide abstract]
    ABSTRACT: A culture medium provides the major environmental conditions for cells in vitro. Replenishment of a culture medium causes an abrupt change in the extracellular environment for maintaining cells in a certain state. As a primitive form of a complex system, a stem cell is likely to be influenced by culture conditions that can change the destination of development. To understand how the change in extracellular environment can influence a biological system, we studied the effect of culture media replacement on the gene expression of differentiating neural progenitor cells. From time-series microarray gene expression data of neural progenitor cells, we observed a periodic wave that was synchronized with intermittent culture media replacement. We identified three modes that mostly contribute to the periodic patterns in gene expression and investigated mode-related genes that are sensitive to the changes in the extracellular environment. The biological significance of the three modes was explored, such as progressive development and cell fate decision, extracellular matrix reassembly, and cell growth regulation in response to stress. In addition, we explored systemic influences of media replacement on differentiating neural progenitor cells. Intermittent culture media replacement interrupts expression of genes that participate in the major processes of differentiating neural progenitor cells. This study shows how the abrupt changes in the cell environment influence gene expression systematically.
    Molecular BioSystems 11/2011; 8(2):602-8. · 3.35 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: A time-series microarray experiment is useful to study the changes in the expression of a large number of genes over time. Many methods for clustering genes using gene expression profiles have been suggested, but it is not easy to interpret the biological significance of the results or utilize these methods for understanding the dynamics of gene regulatory systems. In this study, we introduce an algorithm for readjusting the boundaries of clusters by adopting the advantages of both k-means and singular value decomposition (SVD). In addition, we suggest a methodology for searching the principal genes that can be the most crucial genes in regulation of clusters. We found 34 principal genes from 171 clusters having strong concentratedness in their expression patterns and distinct ranges of oscillatory phases, by using a time-series microarray dataset of mouse embryonic stem (ES) cells after induction of dopaminergic neural differentiation. The biological significance of the principal genes examined in the literature supports the feasibility of our algorithms in that the hierarchy of clusters may lead the manifestation of the phenotypes, e.g., the development of the nervous system.
    Bio Systems 01/2009; 95(1):17-25. · 1.27 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Kaempferol is the major flavonol in green tea and exhibits many biomedically useful properties such as antioxidative, cytoprotective and anti-apoptotic activities. To elucidate its effects on the skin, we investigated the transcriptional profiles of kaempferol-treated HaCaT cells using cDNA microarray analysis and identified 147 transcripts that exhibited significant changes in expression. Of these, 18 were up-regulated and 129 were down-regulated. These transcripts were then classified into 12 categories according to their functional roles: cell adhesion/cytoskeleton, cell cycle, redox homeostasis, immune/defense responses, metabolism, protein biosynthesis/modification, intracellular transport, RNA processing, DNA modification/ replication, regulation of transcription, signal transduction and transport. We then analyzed the promoter sequences of differentially-regulated genes and identified over-represented regulatory sites and candidate transcription factors (TFs) for gene regulation by kaempferol. These included c-REL, SAP-1, Ahr-ARNT, Nrf-2, Elk-1, SPI-B, NF-kappaB and p65. In addition, we validated the microarray results and promoter analyses using conventional methods such as real-time PCR and ELISA-based transcription factor assay. Our microarray analysis has provided useful information for determining the genetic regulatory network affected by kaempferol, and this approach will be useful for elucidating gene-phytochemical interactions.
    Experimental and Molecular Medicine 05/2008; 40(2):208-19. · 2.57 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: The quality of cDNA microarray data is crucial for expanding its application to other research areas, such as the study of gene regulatory networks. Despite the fact that a number of algorithms have been suggested to increase the accuracy of microarray gene expression data, it is necessary to obtain reliable microarray images by improving wet-lab experiments. As the first step of a cDNA microarray experiment, spotting cDNA probes is critical to determining the quality of spot images. We developed a governing equation of cDNA deposition during evaporation of a drop in the microarray spotting process. The governing equation included four parameters: the surface site density on the support, the extrapolated equilibrium constant for the binding of cDNA molecules with surface sites on glass slides, the macromolecular interaction factor, and the volume constant of a drop of cDNA solution. We simulated cDNA deposition from the single model equation by varying the value of the parameters. The morphology of the resulting cDNA deposit can be classified into three types: a doughnut shape, a peak shape, and a volcano shape. The spot morphology can be changed into a flat shape by varying the experimental conditions while considering the parameters of the governing equation of cDNA deposition. The four parameters were estimated by fitting the governing equation to the real microarray images. With the results of the simulation and the parameter estimation, the phenomenon of the formation of cDNA deposits in each type was investigated. This study explains how various spot shapes can exist and suggests which parameters are to be adjusted for obtaining a good spot. This system is able to explore the cDNA microarray spotting process in a predictable, manageable and descriptive manner. We hope it can provide a way to predict the incidents that can occur during a real cDNA microarray experiment, and produce useful data for several research applications involving cDNA microarrays.
    BMC Bioinformatics 02/2007; 8:485. · 3.02 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: We reported previously that genistein enhances the expression of genes involved in fatty acid catabolism through activation of peroxisome proliferator-activated receptor (PPAR) alpha in HepG2 cells, suggesting that genistein holds great promise for therapeutic applications to lipid abnormalities such as obesity and hyperlipidemia in humans. In this study, we examined the changes in hepatic transcriptional profiles using cDNA microarrays in mice with high-fat diet (HFD)-induced obesity supplemented with genistein. C57BL/6J male mice (n = 10/group) were fed a low-fat diet (LFD), a HFD, or a HFD supplemented with 2 g/kg genistein (HFD+GEN) for 12 wk. Mice fed the HFD had abnormal lipid profiles and significantly greater body weight and visceral fat accumulation than the LFD-fed group. Genistein supplementation improved lipid profiles and hepatic steatosis and attenuated the increases in body weight and visceral fat in HFD-fed mice. The cDNA microarrays revealed marked alterations in the expression of 107 genes in the mice fed the HFD and/or the HFD+GEN. Of 97 transcripts altered in the HFD-fed group, 84 genes were normalized by genistein supplementation. However, several genes involved in fatty acid catabolism were not normalized but were still upregulated in the HFD+GEN-fed group, relative to the LFD-fed group. Furthermore, carnitine O-octanoyltransferase, which accelerates fatty acid oxidation, was not affected by the HFD, but was induced by genistein supplementation. These results are consistent with our previous study showing that genistein is an activator of PPAR alpha in vitro. This study showed beneficial effects of genistein supplementation in preventing the development of obesity and metabolic abnormalities in mice with diet-induced obesity. Our results also provide interesting information about the genes associated with the beneficial effects of genistein as well as the mechanisms underlying the development and maintenance of the obesity phenotype in vivo.
    Journal of Nutrition 02/2005; 135(1):33-41. · 4.20 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: To understand the molecular mechanisms underlying alterations in the pathophysiologic status of dietary obesity, we examined hepatic genes differentially expressed in a long-term high-fat intake-induced obesity mouse model. C57BL/6J male mice were fed with two kinds of diets for 12 weeks; a low-fat diet (LFD), a high-fat diet (HFD; n=8), and the expression levels of approximately 10,000 transcripts in liver tissues from the two groups were assessed using cDNA microarray analysis. Twelve-week feeding with the HFD resulted in significant increase in body weight, visceral fat accumulation and circulating cholesterol concentration, compared with the LFD group. The cDNA microarray analysis revealed marked differences in the expressions of 97 hepatic genes. These genes were categorized into seven groups:metabolism; defense, stress, and inflammation responses; signal transduction, apoptosis, and cell cycle; transcription regulation; protein synthesis and modification; transport; and cellular adhesion, cytoskeleton and trafficking. The expression of genes involved in fatty acid catabolism and ketone body synthesis, such as acyl-CoA oxidase1 (Acox1) and HMG-CoA lyase (Hmgcl), was significantly increased, and expression of genes involved in lipogenesis and cholesterol synthesis, such as acetyl-CoA synthetase2 (Acs2), fatty acid synthase (Fasn), and squalene epoxidase (Sqle), was drastically decreased in the HFD group. Interestingly, the genes implicated in defense and stress responses, such as glutathione S-transferases (GSTs) and heat shock proteins (Hsps), were also highly represented in the HFD group. Besides, a number of previously unappreciated regulatory molecules were changed by the HFD. These results revealed a transcriptional adaptation to long-term HFD and provided interesting information about the molecules involved in the development and maintenance of the obesity phenotype in vivo.
    Gene 10/2004; 340(1):99-109. · 2.20 Impact Factor

Publication Stats

322 Citations
73.31 Total Impact Points

Institutions

  • 2002–2014
    • Hanyang University
      • • Graduate School of Biomedical Engineering
      • • Department of Biomedical Science
      • • College of Medicine
      Sŏul, Seoul, South Korea
  • 2004
    • Amorepacific Corporation
      Sŏul, Seoul, South Korea
    • Hanyang University Medical Center
      Sŏul, Seoul, South Korea