• Journal of Ginseng Research
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• v.43 no.3
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• pp.442-451
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• 2019

Background: Ginseng has a wide range of beneficial effects on health, such as the mitigation of minor and major inflammatory diseases, cancer, and cardiovascular diseases. There are abundant data regarding the health-enhancing properties of whole ginseng extracts and single ginsenosides; however, no study to date has determined the receptors that mediate the effects of ginseng extracts. In this study, for the first time, we explored whether the antiinflammatory effects of Rg3-enriched red ginseng extract (Rg3-RGE) are mediated by retinoid X receptor ${\alpha}$-peroxisome-proliferating receptor ${\gamma}$ ($RXR{\alpha}-PPAR{\gamma}$) heterodimer nuclear receptors. Methods: Nitric oxide assay, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazoliumbromide assay, quantitative reverse transcription polymerase chain reaction, nuclear hormone receptor-binding assay, and molecular docking analyses were used for this study. Results: Rg3-RGE exerted antiinflammatory effects via nuclear receptor heterodimers between $RXR{\alpha}$ and $PPAR{\gamma}$ agonists and antagonists. Conclusion: These findings indicate that Rg3-RGE can be considered a potent antiinflammatory agent, and these effects are likely mediated by the nuclear receptor $RXR{\alpha}-PPAR{\gamma}$ heterodimer.

• Journal of Ginseng Research
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• v.43 no.2
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• pp.319-325
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• 2019

Background: Ginsenoside Rf is a ginseng saponin found only in Panax ginseng that affects lipid metabolism. It also has neuroprotective and antiinflammatory properties. We previously showed that Korean Red Ginseng (KRG) inhibited the expression of cyclooxygenase-2 (COX-2) by hypoxia via peroxisome proliferator-activated receptor gamma ($PPAR{\gamma}$). The aim of the current study was to evaluate the possibility of ginsenoside Rf as an active ingredient of KRG in the inhibition of hypoxia-induced COX-2 via $PPAR{\gamma}$. Methods: The effects of ginsenoside Rf on the upregulation of COX-2 by hypoxia and its antimigration effects were evaluated in A549 cells. Docking of ginsenoside Rf was performed with the $PPAR{\gamma}$ structure using Surflex-Dock in Sybyl-X 2.1.1. Results: $PPAR{\gamma}$ protein levels and peroxisome proliferator response element promoter activities were promoted by ginsenoside Rf. Inhibition of COX-2 expression by ginsenoside Rf was blocked by the $PPAR{\gamma}-specific$ inhibitor, T0070907. The $PPAR{\gamma}$ inhibitor also blocked the ability of ginsenoside Rf to suppress cell migration under hypoxia. The docking simulation results indicate that ginsenoside Rf binds to the active site of $PPAR{\gamma}$. Conclusions: Our results demonstrate that ginsenoside Rf inhibits hypoxia induced-COX-2 expression and cellular migration, which are dependent on $PPAR{\gamma}$ activation. These results suggest that ginsenoside Rf has an antiinflammatory effect under hypoxic conditions. Moreover, docking analysis of ginsenoside Rf into the active site of $PPAR{\gamma}$ suggests that the compound binds to $PPAR{\gamma}$ in a position similar to that of known agonists.

• Biomolecules & Therapeutics
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• v.31 no.3
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• pp.312-318
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• 2023

The natural flavonoid macakurzin C (1) exhibited adiponectin biosynthesis-inducing activity during adipogenesis in human bone marrow mesenchymal stem cells and its molecular mechanism was directly associated with a pan-peroxisome proliferator-activated receptor (PPAR) modulator affecting all three PPAR subtypes α, γ, and δ. In this study, increases in adiponectin biosynthesis-inducing activity by macakurzin C derivatives (2-7) were studied. The most potent adiponectin biosynthesis-inducing compound 6, macakurzin C 3,5-dimethylether, was elucidated as a dual PPARα/γ modulator. Compound 6 may exhibit the most potent activity because of the antagonistic relationship between PPARδ and PPARγ. Docking studies revealed that the O-methylation of macakurzin C to generate compound 6 significantly disrupted PPARδ binding. Compound 6 has therapeutic potential in hypoadiponectinemia-related metabolic diseases.

• Radiation Oncology Journal
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• v.30 no.2
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• pp.88-95
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• 2012

Purpose: The fibrates are ligands for peroxisome proliferator-activated receptor (PPAR) ${\alpha}$ and used clinically as hypolipidemic drugs. The fibrates are known to cause peroxisome proliferation, enhance superoxide dismutase (SOD) expression and catalase activity. The antioxidant actions of the fibrates may modify radiation sensitivity. Here, we investigated the change of the radiation sensitivity in two cervix cancer cell lines in combination with fenofibrate (FF). Materials and Methods: Activity and protein expression of SOD were measured according to the concentration of FF. The mRNA expressions were measured by using real time reverse-transcription polymerase chain reaction. Combined cytotoxic effect of FF and radiation was measured by using clonogenic assay. Results: In HeLa cells total SOD activity was increased with increasing FF doses up to 30 ${\mu}M$. In the other hand, the catalase activity was increased a little. As with activity the protein expression of SOD1 and SOD2 was increased with increasing doses of FF. The mRNAs of SOD1, SOD2, $PPAR{\alpha}$ and $PPAR{\gamma}$ were increased with increasing doses of FF. The reactive oxygen species (ROS) produced by radiation was decreased by preincubation with FF. The surviving fractions (SF) by combining FF and radiation was higher than those of radiation alone. In Me180 cells SOD and catalase activity were not increased with FF. Also, the mRNAs of SOD1, SOD2, and $PPAR{\alpha}$ were not increased with FF. However, the mRNA of $PPAR{\gamma}$ was increased with FF. Conclusion: FF can reduce radiation sensitivity by ROS scavenging via SOD induction in HeLa. SOD induction by FF is related with $PPAR{\alpha}$.

• 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 Life Science
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• v.30 no.7
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• pp.640-650
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• 2020

Fibroblast growth factor 21 (FGF21) is an atypical member of the FGF protein family which is highly synthesized in the liver, pancreas, and adipose tissue. Depending on the expression tissue, FGF21 uses endo- or paracrine features to regulate several metabolic pathways including glucose metabolism and energy homeostasis. Different physiologically stressful conditions such as starvation, a ketogenic diet, extreme cold, and mitochondrial dysfunction are known to induce FGF21 synthesis in various tissues to exert either adaptive or defensive mechanisms. More specifically, peroxisome proliferator-activated receptor gamma and peroxisome proliferator-activated receptor alpha control FGF21 expression in adipose tissue and liver, respectively. In addition, the pharmacologic administration of FGF21 has been reported to decrease the body weight and improve the insulin sensitivity and lipoprotein profiles of obese mice and type 2 diabetes patients meaning that FGF21 has attracted huge interest as a therapeutic agent for type 2 diabetes, obesity, and non-alcoholic fatty liver disease. However, understanding FGF21 remains complicated due to the paradoxical condition of its tissue-dependent expression. For example, nutrient deprivation largely increases hepatic FGF21 levels whereas adipose tissue-derived FGF21 is increased under feeding condition. This review discusses the issues of interest that have arisen from existing publications, including the tissue-specific function of FGF21 and its action mechanism. We also summarize the current stage of a clinical trial using several FGF21 analogs.

• Journal of Korean Medicine for Obesity Research
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• v.4 no.1
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• pp.1-11
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• 2004

Objectives: The effects of peroxisome proliferator-activated receptor ${\gamma}2\;(PPAR{\gamma}2)$ Pro12Ala (P12A) polymorphism on body mass index (BMI) and type 2 diabetes are well documented; however, until now, only a few studies have evaluated the effects of this polymorphism on body fat distribution. This study was conducted to elucidate the effects of this polymorphism on computed tomography (CT)-measured body fat distribution and other obesity-related parameters in Korean female subjects. Methods & Results: The frequencies of $PPAR{\gamma}2$ genotypes were: PP type, 93.0%; PA type, 6.8%; and AA type, 0.2%. The frequency of the A allele was 0.035. Body weight (P .012), BMI (P .012), and waist-to-hip ratio (WHR) (P .001) were significantly higher in subjects with PA/AA compared with subjects with PP. When body composition was analyzed by bioimpedance analysis, lean body mass and body water content were similar between the 2 groups. However, body fat mass (P .003) and body fat percent (P .025) were significantly higher in subjects with PA/AA compared with subjects with PP. Among overweight subjects with BMI of greater than 25, PA/AA was associated with significantly higher abdominal subcutaneous fat (P .000), abdominal visceral fat (P .031), and subcutaneous upper and lower thigh adipose tissue (P .010 and .013). However, among lean subjects with BMI of less than 25, no significant differences associated with $PPAR{\gamma}2$ genotype were found, suggesting that the fat-accumulating effects of the PA/AA genotype were evident only among overweight subjects, but not among lean subjects. When serum lipid profiles, glucose, and liver function indicators were compared among overweight subjects, no significant difference associated with $PPAR{\gamma}2$ genotype was found. Changes in body weight, BMI, WHR, and body fat mass were measured among overweight subjects who finished a 1-month weight lose program of a hypocaloric diet and exercise; no significant differences associated with $PPAR{\gamma}2$ genotype were found. Conclusions: The results of this study suggest that the $PPAR{\gamma}2$ PA/AA genotype is associated with increased subcutaneous and visceral fat areas in overweight Korean female subjects, but does not significantly affect serum biochemical parameters and outcomes of weight loss programs.

• Journal of Life Science
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• v.23 no.4
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• pp.510-517
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• 2013

This study was performed to evaluate the antiobesity effect of supercritical fluid extracts (SFC) and marc methanol extracts (SFM) from Cinnamomum verum in 3T3-L1 preadipocytes. In inducing the differentiation of 3T3-L1 preadipocytes in the presence of an adipogenic cocktail, iso-butylmethylanthine (IBMX), dexamathasone, and insulin, treatment with fraction residue SFC and SFM. SFC significantly reduced the mRNA expression of the transcription factor peroxisome proliferator-activate-dreceptor-${\gamma}$ ($PPAR{\gamma}$), the sterol regulatory-element-binding protein-1c (SREBP1c), and the CCAAT enhancer-binding-protein ${\alpha}$ ($C/EBP{\alpha}$) in a concentration-dependent manner. Moreover, SFC markedly down-regulated acyl-CoA synthetase-1 (ASC1), fatty acid synthesis (FAS), fatty acid transport-1 (FATP1), fatty acid binding protein 4 (FABP4), and perilipin. These findings suggest that SFC may be a potential therapeutic adjunct for obesity by targeting the differentiation of preadipocytes, as well as their functions.

• Molecules and Cells
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• v.37 no.1
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• pp.74-80
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• 2014

The peroxisome is an intracellular organelle that responds dynamically to environmental changes. Various model organisms have been used to study the roles of peroxisomal proteins in maintaining cellular homeostasis. By taking advantage of the zebrafish model whose early stage of embryogenesis is dependent on yolk components, we examined the developmental roles of the D-bifunctional protein (Dbp), an essential enzyme in the peroxisomal ${\beta}$-oxidation. The knockdown of dbp in zebrafish phenocopied clinical manifestations of its deficiency in human, including defective craniofacial morphogenesis, growth retardation, and abnormal neuronal development. Overexpression of murine Dbp rescued the morphological phenotypes induced by dbp knockdown, indicative of conserved roles of Dbp during zebrafish and mammalian development. Knockdown of dbp impaired normal development of blood, blood vessels, and most strikingly, endoderm-derived organs including the liver and pancreas - a phenotype not reported elsewhere in connection with peroxisome dysfunction. Taken together, our results demonstrate for the first time that zebrafish might be a useful model animal to study the role of peroxisomes during vertebrate development.

• Proceedings of the PSK Conference
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• 2000.04a
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• pp.139.2-139.2
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• 2000