• Title/Summary/Keyword: PPAR

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PPAR-Gamma Pro12Ala Polymorphism and Gastric Cancer Risk in a Turkish Population

  • Canbay, Emel;Kurnaz, Ozlem;Canbay, Bahar;Bugra, Dursun;Cakmakoglu, Bedia;Bulut, Turker;Yamaner, Sumer;Sokucu, Necmettin;Buyukuncu, Yilmaz;Yilmaz-Aydogan, Hulya
    • Asian Pacific Journal of Cancer Prevention
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    • v.13 no.11
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    • pp.5875-5878
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    • 2012
  • Background: Peroxisome proliferator-activated receptor gamma ($PPAR{\gamma}$) is a ligand dependent transcription factor involved in various processes, including carcinogenesis. We aimed to investigate any possible association of the $PPAR{\gamma}$ Pro12Ala (rs1801282) polymorphism with risk of developing gastric cancer (GC). Patients and Methods: A hospital based case control study was designed covering 50 patients with GC and 120 healthy controls. The frequencies of $PPAR{\gamma}$ Pro12Ala (rs1801282) were determined using a polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) assay. Results: The Ala12 allele of the $PPAR{\gamma}$ Pro12Ala G gene was associated with a 1.95 fold increased risk of GC development (p: 0.022; 95% CI: 1.58-2.40). Subgroup analyses showed that the same allele was also associated with metastasis (p: 0.000; OR:4.09; 95%CI:2.273-7.368) and differentiation (p: 0.004; OR:1.95; 95%CI:1.335-2.875) in patients with GC. Conclusion: This study suggests that the $PPAR{\gamma}$ Pro12Ala G (Ala12) allele might be associated with development, differentiation and metastatic process of GC in the Turkish population. Further studies conducted in larger study groups and in different ethnic populations will be needed to clarify the exact role of the $PPAR{\gamma}$ Pro12Ala polymorphism in GC.

The Anti-obesity Effects of Gambi-hwan Extract on Obese Rats Induced by High-fat Diet through the Expression of UCP-1 and PPAR-${\delta}$

  • Lee, Beom-Joon;Ryu, Jae-Hwan;Kim, Jae-Wan;Park, Jong-Hun;Park, Jae-Woo
    • The Journal of Korean Medicine
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    • v.28 no.4
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    • pp.136-147
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    • 2007
  • Objective : Recently there are a lot of attempts to treat obesity through energy expenditure. Especially UCP-1 and PPAR-${\delta}$ is known to play a key role for energy dissipation through the increasing thermogenesis. Gambi-hwan extract is a traditional medicine made of herbs containing the polyunsaturate fatty acids related to the energy expenditure. It is expected to reduce the weight by means of the expression of UCP-1 and PPAR-${\delta}$. Meterial and Method : We divided 21 rats into 3 groups and assigned 8 rats respectively. The normal group was administered normal diet, the control group was administered high-fat diet, and the G50 group was administered high-fat diet with Gambi-hwan extracts50 mg/kg. And then the weights of body, food intake, the changes of lipids in blood stream, and the expressions of UCP-1 and PPAR-${\delta}$ on adipose tissues were measured respectively. Result : The reduction of body weight and the increasing tendency of expression of UCP-1 and PPAR-${\delta}$ mRNA were shown in G50 group. In the G50 group the Triglyceride level is decreased and the HDL-cholesterol level and the expression of PPAR-${\delta}$ and UCP-1 protein on Visceral adipose tissue were significantly increased. Conclusion : This result indicates that Gambi-hwan Extract upregulate the expression of UCP-1 and PPAR-${\delta}$ in adipose tissue, which may contribute to reducing the weight of adipose tissue.

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Expression of Peroxisome Proliferator-Activated Receptor Gamma in Helicobacter Pylori-associated Mouse Gastric Cancer Tissue and Human Gastric Epithelial Cells.

  • Oh, Sang-yeon;Nam, Ki-taek;Jang, Dong-deuk;Yang, Ki-hwa;Hahm, Ki-baik;Kim, Dae-yong
    • Proceedings of the Korean Society of Veterinary Pathology Conference
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    • 2003.10a
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    • pp.11-11
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    • 2003
  • Peroxisome proliferator-activated receptor (PPAR) is nuclear hormone receptors that can be activated by a variety of compounds. Two PPAR gamma isoforms are expressed at the protein level in mouse, gamma 1 and gamma 2. And PPAR gamma is intimately associated with cell differentiation and proliferation[1]. So aim of this study, investigated where express PPAR gamma in mouse gastric cancer tissues, including human gastric cancer cell lines and expression pattern of PPAR gamma. (omitted)

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Blood lipid lowering effect of butanol extract from Galkun-Whanglyeon-Whanggum-Tang (갈근황련황금탕 부탄올 추출물의 혈중에서의 지질 개선효과)

  • Lee, Keyong Ho;Kim, Choong-Hwan;Rhee, Ki-Hyeong
    • Korean Journal of Pharmacognosy
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    • v.44 no.4
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    • pp.397-401
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    • 2013
  • The Galkun-Whanglyeon-Whanggum-Tang, an officially standardized mixture of traditional herbal medicines used in Korea and China, consists of Pueraria lobata, Scullellaria baicalensis, Coptis chinensis and Glycyrrhiza uralensis at a ratio of 6:9:3:2.4. In this study, we evaluated the effect of lowering lipid accumulation in blood by treatment of Galkun-Whanglyeon-Whanggum-Tang in Apo E(-/-) atherosclerotic animal model. ApoE/mice fed with 1.25% cholesterol, 7.5% cocoa butter and 0.5% sodium cholate diet were orally given vehicle or Galkun-Whanglyeon-Whanggum-Tang(10, 100 and 300 mg/kg/day) for 12 weeks. Serum levels of triglyceride(TG), total cholestrerol(TC), low-density lipoprotein(LDL) and high-density lipoprotein(HDL) were analyzed, and PPAR-${\alpha}$ and PPAR-${\gamma}$ were examined by Western blotting analysis. Galkun-Whanglyeon- Whanggum-Tang decreased serum levels of TG, TC and LDL, but not HDL in ApoE/mice. In parallel, Galkun-Whanglyeon-Whanggum-Tang treatment showed the increased activity of PPAR-${\alpha}$ and PPAR-${\gamma}$ in hepatocytes. In summary, Galkun-Whanglyeon-Whanggum-Tang can reduce lipid accumulation in blood, and this effect might be accompanied by the upregulation of PPAR-${\alpha}$ and PPAR-${\gamma}$ in Apo E(-/-) atherosclerotic mouse model.

Sexually Dimorphic Control of Obesity and Skeletal Muscle Lipid Metabolism by Fenofibrate

  • Lim, Hyesook;Lee, Hyunghee;Yoon, Michung
    • Biomedical Science Letters
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    • v.19 no.1
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    • pp.17-24
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    • 2013
  • Animals show a sexual dimorphism in metabolic responses. We investigated to verify whether the peroxisome proliferator-activated receptor ${\alpha}$ ($PPAR{\alpha}$) agonist fenofibrate regulates obesity and skeletal muscle lipid metabolism with sexual dimorphism and to determine the changes in skeletal muscle expression of $PPAR{\alpha}$ target genes. After both sexes of C57BL/6J mice received a high fat diet with or without fenofibrate for 7 weeks, we examined the effects of fenofibrate on not only body weight, adipose tissue mass, and skeletal muscle lipid accumulation, but also the mRNA expression of $PPAR{\alpha}$-related genes in skeletal muscle. Male mice given a fenofibrate-supplemented high fat diet showed decreased body weight gain and adipose tissue mass compared with mice fed a high fat diet alone, whereas fenofibrate did not reduce them in high fat diet-fed female mice. Lipid accumulation in skeletal muscle was inhibited by fenofibrate in male mice, but not in female mice. Gene expression analysis revealed that fenofibrate increased the mRNA levels of $PPAR{\alpha}$ target enzymes only in male mice. Therefore, our results suggest that sex-dependence differences in obesity and intramuscular lipid levels under fenofibrate treatment could be due in part to the differences in skeletal muscle $PPAR{\alpha}$ activation between male and female mice.

$17{\beta}$-estradiol Represses White Adipose Tissue Metabolism by Inhibiting $PPAR{\gamma}$ in High Fat Diet-induced Obese Female Ovariectomized Mice

  • Yoon, Mi-Chung;Jeong, Sun-Hyo
    • Biomedical Science Letters
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    • v.15 no.3
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    • pp.171-177
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    • 2009
  • This study investigated whether increased adiposity is prevented by estrogen replacement in female ovariectomized (OVX) C57BL/6J mice, an animal model of human menopause and whether these metabolic changes reflect the inhibitory action of estrogen on peroxisome proliferator-activated receptor $\gamma$ ($PPAR{\gamma}$)-regulated gene expression. Treatment of $17{\beta}$-estradiol for the last one week of the experiment decreased high fat diet-induced body weight gain and white adipose tissue mass compared to OVX control mice. Histological analysis showed that administration of $17{\beta}$-estradiol to mice decreased the size of adipocytes in parametrial adipose tissue versus OVX control mice. In addition, $17{\beta}$-estradiol reduced the adipose expression of $PPAR{\gamma}$ as well as $PPAR{\gamma}$ target genes such as adipocyte fatty acid binding protein and tumor necrosis factor $\alpha$. These results suggest that $17{\beta}$-estradiol may inhibit adiposity through reducing the $PPAR{\gamma}$ activities in female OVX mice.

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Liver PPAR${\alpha}$ and UCP2 are Involved in the Regulation of Ovariectomy-Induced Adiposity and Steatosis by Swim Training

  • Jeong, Sun-Hyo;Yoon, Mi-Chung
    • 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.

Anti-metastatic Effect of Natural Product-motivated Synthetic PPAR-γ Ligands

  • Li, Dan-dan;Wang, Ying;Ju, Zhiran;Kim, Eun La;Hong, Jongki;Jung, Jee H.
    • Natural Product Sciences
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    • v.28 no.2
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    • pp.80-88
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    • 2022
  • Colorectal cancer is one of the most common cancers globally, ranking second for the number of cancer-related deaths. Metastasis has been reported as the main cause of death in patients with colorectal cancer. Peroxisome proliferator-activated receptor gamma (PPAR-γ) is a transcription factor that functions as a tumor suppressor by inhibiting cellular proliferation, migration, and invasion. In our previous efforts to generate natural product-motivated PPAR-γ ligands, the compounds 1 and 2 were obtained. These compounds activated PPAR-γ and inhibited the migration and invasion of HCT116 colorectal cancer cells, and they were also found to inhibit the epithelial-to-mesenchymal transition, which is a key process in cancer metastasis. Compounds 1 and 2 upregulated expression of the epithelial marker (E-cadherin), and downregulated expression of the mesenchymal marker (N-cadherin) and transcriptional factor (Snail). Therefore, the PPAR-γ agonists 1 and 2 could serve as a valuable model for the study on anti-metastatic leads for the treatment of colorectal cancer.

Changes in mRNA Expression of Obesity-related Genes by GyeongshinhaeGihwan 1 (GGT1) in hGHTg (human growth hormone transgenic) obese Female Rats (암컷 hGHTg 비만 쥐에서 경신해지환(輕身解脂丸) (GGT1)에 의한 비만관련 유전자 mRNA 발현의 변화)

  • Yoon, Ki-Hyeon;Yoon, Mi-Chung;Kim, Hoon;Shin, Soon-Shik
    • Journal of Physiology & Pathology in Korean Medicine
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    • v.20 no.2
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    • pp.383-387
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    • 2006
  • To investigate the effect of GyeongshinhaeGihwan 1(GGT1) frequently used as an anti-obesity herbal medicine in oriental medicine on the expression of obesity-related genes, we measured the changes in mRNA levels of these genes by GGT1 in human growth hormone transgenic (hGHTg) obese female rats, and these effects by GGT1 were compared with those of reductil (RD), an anti-obesity drug approved by FDA. Rats received once daily oral administrations of autoclaved water, RD, or GGT1 for 8 weeks. At the end of study, rats were sacrificed and tissues were harvested. Total RNA from adipose tissue, liver and kidney was prepared and the mRNA levels for LPL (lipoprotein lipase), $PPAR{\gamma}$ (peroxisome proliferator activated receptor-gamma), $PPAR{\delta}$ (peroxisome proliferator activated receptor-delta), leptin, $TNF{\alpha}$ (tumor necrosis factor-alpha), and internal standard G3PDH (glyceraldehyde-3-phosphate dehydrogenase) were analyzed by RT-PCR. Compared with control group, $PPAR{\gamma}$ mRNA levels of liver and kidney were decreased in both RD and GGT1 groups, and the effects were more prominent in GGT1 group than in RD group, suggesting that GGT1 is effective in the inhibition of lipid storage by decreasing the $PPAR{\gamma}$ expression. $PPAR{\delta}$ mRNA levels of adipose tissue were increased by RD and GGT1 compared with DW, and the magnitude of increase were higher in GGT1 group than in RD group, indicating that GGT1 stimulates fatty acid oxidation and energy metabolism by activating $PPAR{\delta}$ expression. GGT1 group had higher concentrations of serum leptin, a well-known inhibitor of appetite, than control and RD groups. However, The mRNA levels of leptin, LPL, and $TNF{\alpha}$ were not changed by GGT1. These results indicate that GGT1 can prevent obesity in hGHTg obese female rats by down-regulating and up-regulating the mRNA expression of $PPAR{\gamma}$ and $PPAR{\delta}$, respectively, and that this anti-obesity effects were more pronounced in GGT1 group compared with RD group. In addition, GGT1 seems to inhibit obesity by increasing the circulating leptin levels.

The Effects of Dietary Interventions on mRNA Expression of Peroxisome Proliferator Activated Receptor Isoforms (PPAR Isoforms) in Rat Skeletal Muscle (장기간의 고지방 식이 섭취가 골격근 내 PPAR Isoforms 유전자 발현에 미치는 영향)

  • Lee, Jang-Kyu;Kim, Jung-Kyu;Moon, Hee-Won;Shin, Young-Oh;Lee, Jong-Sam
    • Journal of Nutrition and Health
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    • v.40 no.3
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    • pp.221-228
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    • 2007
  • We determined the effects of dietary manipulations on messenger RNA of peroxisome proliferators activated receptor isoforms (i.e., PPAR ${\alpha},\;{\beta}/{\delta},\;{\gamma}$) in red vastus lateralis muscle of rats. Total 16 male Sprague-Dawley rats were used, and animals were divided into one of two dietary conditions: either chow diet group (CHOW; n=8) in which animals were 134 with standard rodent chow (61.8% carbohydrate, 15.7% fat, 22.5% protein) or high fat diet group (FAT n=8) in which animals were fed 24.3% carbohydrate, 52.8% fat, 22.9% protein. At the end of the 8 weeks of experimental period, red vastus lateralis muscle was dissected out from all animals, and PPAR ${\alpha},\;{\beta}/{\delta},\;{\gamma}$ mRNA expression was determined. There was no significant difference in body mass (BM) between CHOW and FAT. As expected, blood glucose and free fatty acid (FFA) concentration was higher in FAT than CHOW (p<0.05), and lactate concentration was significantly lower in FAT compared to CHOW (p<0.05). Insulin concentration tended to higher in FAT than CHOW ($67.2{\pm}21.9\;vs.\;27.0{\pm}5.2$ pmol/L), but it did not reach to the statistical significance. Gene expression of PPAR ${\alpha}$ was not significantly different between CHOW and FAT. It was not also significantly different in PPAR ${\beta}/{\delta}$. Interestingly, expression of mRNA in PPAR ${\gamma}$ however, was markedly depressed in FAT compared to CHOW (approximately 3 fold higher in CHOW; p<0.05). Results obtained from present study implies that PPAR ${\gamma}$ (as compensatory function of PPAR ${\alpha}$ is expressed) possibly exerts another major tuning roles in fatty acid transport, utilization, as well as biosynthesis in skeletal muscle cells. The situations and conditions that can be postulated for this implication need to be further examined.