• Title/Summary/Keyword: PPAR$\gamma$

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Effects of d-${\alpha}$-tocopherol supplements on lipid metabolism in a high-fat diet-fed animal model

  • Kim, Do Yeon;Kim, Jinkyung;Ham, Hye Jin;Choue, Ryowon
    • Nutrition Research and Practice
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    • v.7 no.6
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    • pp.481-487
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    • 2013
  • High-fat diet up-regulates either insulin resistance or triglycerides, which is assumed to be related to the expression of peroxisome proliferator-activated receptor (PPAR)-${\alpha}$ and PPAR-${\gamma}$. The beneficial effects of vitamin E on insulin resistance are well known; however, it is not clear if vitamin E with a high-fat diet alters the expression of PPAR-${\alpha}$ and PPAR-${\gamma}$. We investigated the effects of d-${\alpha}$-tocopherol supplementation on insulin sensitivity, blood lipid profiles, lipid peroxidation, and the expression of PPAR-${\alpha}$ and PPAR-${\gamma}$ in a high-fat (HF) diet-fed male C57BL/6J model of insulin resistance. The animals were given a regular diet (CON; 10% fat), a HF diet containing 45% fat, or a HF diet plus d-${\alpha}$-tocopherol (HF-E) for a period of 20 weeks. The results showed that the HF diet induced insulin resistance and altered the lipid profile, specifically the triglyceride (TG) and total cholesterol (TC) levels (P < 0.05). In this animal model, supplementation with d-${\alpha}$-tocopherol improved insulin resistance as well as the serum levels of TG and very-low-density lipoprotein-cholesterol (VLDL-C) (P < 0.05). Moreover, the treatment decreased the levels of malondialdehyde (MDA) in the serum and liver while increasing hepatic PPAR-${\alpha}$ expression and decreasing PPAR-${\gamma}$ expression. In conclusion, the oral administration of d-${\alpha}$-tocopherol with a high-fat diet had positive effects on insulin resistance, lipid profiles, and oxidative stress through the expression of PPAR-${\alpha}$ and PPAR-${\gamma}$ in a high-fat diet-fed male mice.

The Antiallergic Effects of Yeotaectonggi-tang (YTT) on the Mice Model with Allergic Rhinitis by Regulation of PPAR-$\gamma$ (PPAR-$\gamma$ 조절을 통한 여택통기탕(麗澤通氣湯)의 항알레르기와 항염증 효과)

  • Son, Jung-Min;Hong, Seung-Ug
    • The Journal of Korean Medicine Ophthalmology and Otolaryngology and Dermatology
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    • v.23 no.2
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    • pp.109-124
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    • 2010
  • Objectives : The aim of this study is to investigate the antiallergic effects of YTT on allergic rhinitis by regulation of peroxisome proliferator-activated receptor gamma (PPAR-$\gamma$). Methods : The thirty rats were divided into three groups : normal group, control (allergic rhinitis elicited) group, sample (Yeotaectonggi-tang treated after allergic rhinitis elicitation) group. To induce allergic rhinitis in control group and sample group, rats were sensitized intraperitoneally with 0.1% ovalbumin(OVA) solution 3 times at intervals of 1 week. Then intranasal sensitization was performed by diffusing 0.1% ovalbumin(OVA) solution 3 times at intervals of 2 days. After that time rats in sample group were oral administration treated by YTT for 7days. The change of the amounts of eosinophil, substance P, MIP-2, PPAR-$\gamma$, IL-4, iNOS were observed in each group. we used the statistical method of ANOVA test(p<0.05). Results : The number of eosinophil in sample group noticeably decreased than control group. And the decrease of substance P and MIP-2 positive reaction were observed in mucosa. YTT inhibited IL-4 and iNOS production, mucus secretion, activation of mast cells and fibrosis remodeling by regulation of PPAR-$\gamma$ activation. Conclusion : According to the above results, it is considered that YTT mitigated mucosa damage on the mice model with allergic rhinitis by regulation of PPAR-$\gamma$.

Biapigenin, Candidate of an Agonist of Human Peroxisome Proliferator-Activated Receptor γ with Anticancer Activity

  • Kim, Jin-Kyoung;Shin, So-Young;Lee, Jee-Young;Lee, So-Jung;Lee, Eun-Jung;Jin, Qinglong;Lee, June-Young;Woo, Eun-Rhan;Lee, Dong-Gun;Yoon, Do-Young;Kim, Yang-Mee
    • Bulletin of the Korean Chemical Society
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    • v.32 no.8
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    • pp.2717-2721
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    • 2011
  • Peroxisome proliferator-activated receptors (PPARs) are a subfamily of nuclear receptors (NRs). Human peroxisome proliferator-activated receptor gamma (hPPAR${\gamma}$) has been implicated in the pathology of numerous diseases, including obesity, diabetes, and cancer. ELISA-based hPPAR${\gamma}$ activation assay showed that biapigenin increased the binding between hPPAR${\gamma}$ and steroid receptor coactivator-1 (SRC-1) by approximately 3-fold. In order to confirm that biapigenin binds to hPPAR${\gamma}$, fluorescence quenching experiment was performed. The results showed that biapigenin has higher binding affinity to hPPAR${\gamma}$ at nanomolar concentrations compared to indomethacin. Biapigenin showed anticancer activity against HeLa cells. Biapigenin was noncytotoxic against HaCa T cell. All these data implied that biapigenin may be a potent agonist of hPPAR${\gamma}$ with anticancer activity. We will further investigate its anticancer effects against human cervical cancer.

Effects of HyangsosanGamibang on the $PPAR{\gamma}$ in the bronchial asthma mouse model (천식 백서(喘息 白鼠)에서 향소산가미방(香蘇散加味方)의 $PPAR{\gamma}$에 대한 효과)

  • Park, Eun-Jung;Lee, Hai-Ja;Oh, Ji-Eun
    • The Journal of Pediatrics of Korean Medicine
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    • v.21 no.1
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    • pp.41-51
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    • 2007
  • 목적 : OVA에 유도된 천식 쥐 모델에 향소산가미방을 투여한 후 $PPAR{\gamma}$의 변화를 조사하여 향소산가미방의 천식 치료 기전을 알아보고자 하였다. 대상 및 방법 : 8주된 암컷 BALB/c 마우스에 첫 날과 14일 후에 20 ${\mu}g$의 OVA를 알루미니윰 하이드록사이드 1mg과 혼합한 후 총 200 ${\mu}g$를 복강 내로 주입하여 감작시켰다. 처음 감작시킨 날로부터 21,22,23일 후에 천식 모델에 사용하는 초음파 분무기를 이용하여 세 번째 감작시켜서 천식 마우스 모델을 만들었다. 천식 마우스 모델을 만드는 기간 중 OVA를 복강 내로 주입한 후 19일째에 24시간의 간격으로 향소산가미방을 7일 동안 경구 투여하여 향소산가미방의 효과를 조사하였다. 기관지폐포세척술은 마지막 감작 후 72시간 후에 실행하고 기관지폐포 세척액의 총 세포수를 측정하였다. $PPAR{\gamma}$의 발현은 천식 마우스 모델의 폐와 향소산가미방을 투여한 마우스 모델의 폐를 적출한 후 Western blotting 방법을 아용하여 측정하였다. 병리 조직학적 검사는 hematoxylin 2 and eosin-Y 염색을 이용하여 조사하였다. 결과 : 정상 군과 비교하여 OVA감작 천식 쥐 모델에서는 72시간 후에 총 세포 수가 증가하였다. 특히 OVA감작 천식 군에서 증가된 호산구의 수가 향소산가미방을 투여 한 쥐 군에서는 유의하게 감소하였다. OVA감작 천식 쥐 모델에서 72시간 후에 정상 군과 비교하여 핵 내에서의 $PPAR{\gamma}$단백질의 발현이 약간 증가하였다. 그러나 향소산가미방을 투여한 쥐 모델에서는 세포질과 핵 내에서 $PPAR{\gamma}$단백질의 발현이 유의하게 증가하였다. 조직학적 검사상 정상 군과 비교하여 OVA 감작된 천식 쥐 모델에서는 폐포, 세기관지, 기도내강 주변에 많은 염증 세포들이 있었다. 그러나 가미향소산 을 투여 한 후에는 염증 세포들이 유의하게 감소하였다. 결론 : 가미향소산은 $PPAR{\gamma}$작용제로서 역할을 하며, 천식에 대한 치료제 또는 예방제를 개발하는 데 후보 물질이 될 것으로 사료된다.

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Inhibition of miR-128 Abates Aβ-Mediated Cytotoxicity by Targeting PPAR-γ via NF-κB Inactivation in Primary Mouse Cortical Neurons and Neuro2a Cells

  • Geng, Lijiao;Zhang, Tao;Liu, Wei;Chen, Yong
    • Yonsei Medical Journal
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    • v.59 no.9
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    • pp.1096-1106
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    • 2018
  • Purpose: Alzheimer's disease (AD) is the sixth most common cause of death in the United States. MicroRNAs have been identified as vital players in neurodegenerative diseases, including AD. microRNA-128 (miR-128) has been shown to be dysregulated in AD. This study aimed to explore the roles and molecular mechanisms of miR-128 in AD progression. Materials and Methods: Expression patterns of miR-128 and peroxisome proliferator-activated receptor gamma ($PPAR-{\gamma}$) messenger RNA in clinical samples and cells were measured using RT-qPCR assay. $PPAR-{\gamma}$ protein levels were determined by Western blot assay. Cell viability was determined by MTT assay. Cell apoptotic rate was detected by flow cytometry via double-staining of Annexin V-FITC/PI. Caspase 3 and $NF-{\kappa}B$ activity was determined by a Caspase 3 Activity Assay Kit or $NF-{\kappa}B$ p65 Transcription Factor Assay Kit, respectively. Bioinformatics prediction and luciferase reporter assay were used to investigate interactions between miR-128 and $PPAR-{\gamma}$ 3'UTR. Results: MiR-128 expression was upregulated and $PPAR-{\gamma}$ expression was downregulated in plasma from AD patients and $amyloid-{\beta}$ $(A{\beta})-treated$ primary mouse cortical neurons (MCN) and Neuro2a (N2a) cells. Inhibition of miR-128 decreased $A{\beta}-mediated$ cytotoxicity through inactivation of $NF-{\kappa}B$ in MCN and N2a cells. Moreover, $PPAR-{\gamma}$ was a target of miR-128. $PPAR-{\gamma}$ upregulation attenuated $A{\beta}-mediated$ cytotoxicity by inactivating $NF-{\kappa}B$ in MCN and N2a cells. Furthermore, $PPAR-{\gamma}$ downregulation was able to abolish the effect of anti-miR-128 on cytotoxicity and $NF-{\kappa}B$ activity in MCN and N2a cells. Conclusion: MiR-128 inhibitor decreased $A{\beta}-mediated$ cytotoxicity by upregulating $PPAR-{\gamma}$ via inactivation of $NF-{\kappa}B$ in MCN and N2a cells, providing a new potential target in AD treatment.

Anti-adipogenic Effect of Undaria pinnatifida Extracts by Ethanol in 3T3-L1 Adipocytes (미역 에탄올 추출물이 지방세포 형성과정에 미치는 영향)

  • Kim, Hye-Jin;Kang, Chang-Han;Kim, Sung-Koo
    • Journal of Life Science
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    • v.22 no.8
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    • pp.1052-1056
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    • 2012
  • Undaria pinnatifada has been used as a natural diet food with few calories and as a source of iodine. Even though U. pinnatifida has been regarded as a diet food, the mechanisms of its inhibitory effects on adipocyte differentiation and the accumulation of fat in adipocytes are poorly understood. In this study, the effect and mechanism of U. pinnatifida ethanol extract on 3T3-L1 differentiation into adipocytes were investigated. The effects of U. pinnatifida ethanol extract on cell viability and the anti-adipogenic effect were investigated via MTT assay, Oil red O staining, RT-PCR, and western blot. The U. pinnatifida ethanol extract did not show toxicity up to a concentration of 50 ${\mu}g/ml$. The addition of U. pinnatifida ethanol extract decreased triglyceride contents by 40% when 50 ${\mu}g/ml$ of U. pinnatifida ethanol extract was added during 3T3-L1 differentiation and adipocyte triglyceride formation. The transcription and expression of peroxisome proliferator-activated receptor ${\gamma}$ ($PPAR{\gamma}$), leptin, and hormone-sensitive lipase (HSL) as adipocyte-specific proteins were determined by RT-PCR and western blot. The overexpression of $PPAR{\gamma}$ could accelerate adipocyte differentiation. Also, leptin was secreted for triglyceride accumulation in the adipocytes and the increase of adipocyte cell size. Thus, $PPAR{\gamma}$ and leptin were used as indicators of obesity. $PPAR{\gamma}$ and leptin were repressed by the increased addition of U. pinnatifida ethanol extract. This indicates that U. pinnatifida was effective as an anti-obesity agent by repressing the differentiation of 3T3-L1 into adipocytes and inhibiting triglyceride formation in adipocytes.

Synthesis of thiazolidinedione analogs

  • Yun, Hyun-Jin;Cheon, Seung-Hoon
    • Proceedings of the PSK Conference
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    • 2003.10b
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    • pp.177.2-177.2
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    • 2003
  • Thiazolidinediones (TZDs) are a new class of compound that increase insulin sensitivity in type 2 diabetic patients. Thiazolidinediones (TZDs) act as ligands for a member of the nuclear hormone receptor superfamily, peroxisome proliferator-activated receptor-$\gamma$ (PPAR-$\gamma$), which is highly expressed in fatty tissue and, moreover, has been shown to play an important role in fat cell differentiation. The strong interaction between the antidiabetic activity ofTZDs and their ability to activate PPAR-$\gamma$ suggests that PPAR-$\gamma$, through downstream-regulated genes, mediates the effects of TZDs. (omitted)

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The Association between Peroxisome Proliferator-Activated Receptor-Gamma C161T Polymorphism and Type 2 Diabetic Complications (제 2형 당뇨병 및 당뇨 합병증의 발생과 Peroxisome Proliferator-Activated Receptor-$\gamma2$ C161T 유전자 다형성과의 관계)

  • Lee, Byung-Cheol;Ahn, Se-Young;Doo, Ho-Kyung;Ahn, Young-Min
    • The Journal of Internal Korean Medicine
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    • v.28 no.4
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    • pp.902-910
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    • 2007
  • Objective : Peroxisome proliferator-activated receptor (PPAR)-gamma, a transcription factor in adipocyte differentiation, has important effects on insulin sensitivity, atherosclerosis, endothelial cell function and inflammation. Through these effects, PPAR-gamma2 might be involved with type 2 diabetes and vascular disease, including diabetic complications. Recently, it has been reported that the C161T polymorphism in the exon 6 of PPAR-gamma is associated with type 2 diabetes interacting with uncoupling protein 2 (UCP2) gene, and is associated with acute myocardial infarction. We studied the association of this polymorphism with type 2 diabetes and its complications, such as retinopathy, ischemic stroke, nephropathy and neuropathy in Korean non-diabetic and type 2 diabetic populations. Methods : Three hundred and thirty eight type 2 diabetic patients (retinopathy: 64, ischemic stroke: 67, nephropathy: 39 and neuropathy: 76) and 152 healthy matched control subjects were evaluated. The PPAR-gamma C161T polymorphism was analyzed by PCR-RFLP. Results : PPAR-gamma C161T genotype and allele frequency did not show significant differences between type 2 diabetic patients and healthy controls (T allele: 17.0 vs. 14.5, OR= 1.21, P=0.3188). In the analysis for diabetic complications, T allele in diabetic nephropathy was significantly higher than controls (P=0.0358). T allele in the ischemic stroke patients was also higher than healthy controls, although it had no significance (P=0.1375). Conclusions : These results suggest that the C161T polymorphism of the PPAR-gamma gene might be associated with diabetic nephropathy in type 2 diabetes.

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Anti-Obesity Effect of Ethyl Acetate Extracts from Agrimonia pilosa Ledeb. in 3T3-L1 Preadipocytes (3T3-L1 지방전구세포에서 용아초 에틸아세테이트 추출물의 항비만 효과)

  • Lee, Jung-A;Ahn, Eun-Kyung;Hong, Seong-Su;Oh, Joa-Sub
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.41 no.2
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    • pp.161-167
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    • 2012
  • To evaluate the anti-obesity effect of Agrimonia pilosa L., this study investigated that ethyl acetate extract from A. pilosa L. (EAAP) suppresses lipid accumulation and inhibits expression of adipogenic marker genes, such as peroxisome proliferator activated receptor ${\gamma}$ (PPAR${\gamma}$), CCAAT-enhancer-binding protein ${\alpha}$ (C/EBP${\alpha}$), glucose transporter 4 (GLUT4), and adiponectin in 3T3-L1 preadipocytes. We demonstrated that EAAP inhibited adipocyte differentiation and expression of PPAR${\gamma}$ and C/EBP${\alpha}$ mRNA levels in a dose-dependent manner. In addition, EAAP reduced the PPAR${\gamma}$ transcriptional activity stimulated by rosiglitazone in HEK 293T cells and decreased the expression of GLUT4 and adiponectin in 3T3-L1 cells. These results suggest that EAAP inhibits preadipocyte differentiation and adipogenesis by blocking of PPAR${\gamma}$ and C/EBP${\alpha}$ gene expression in 3T3-L1 cells.

Polysaccharides from Edible Mushroom Hinmogi (Tremella fuciformis) Inhibit Differentiation of 3T3-L1 Adipocytes by Reducing mRNA Expression of $PPAR{\gamma}$, C/$EBP{\alpha}$, and Leptin

  • Jeong, Hye-Jin;Yoon, Seon-Joo;Pyun, Yu-Ryang
    • Food Science and Biotechnology
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    • v.17 no.2
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    • pp.267-273
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    • 2008
  • Water-soluble fraction (WSF) from edible mushroom hinmogi (Tremella fuciformis) were obtained by water extraction, and polysaccharides in the WSF were separated by ethanol precipitation. The inhibitory effects of the polysaccharides on 3T3-L1 adipocyte differentiation were evaluated by the reduction of peroxisome proliferators-activated receptor ${\gamma}$ ($PPAR{\gamma}$) translation, triglyceride accumulation, Oil Red-O staining, and expression levels of $PPAR{\gamma}$, CCAAT/enhancer binding protein a (C/$EBP{\alpha}$), and leptin. The $PPAR{\gamma}$ translation in 3T3-L1 cells was inhibited by the treatment with polysaccharide precipitated by 80% ethanol (P80) which showed highest inhibitory activity among polysaccharides tested. In addition, treatment of P80 to 3T3-L1 cells significantly inhibited the triglyceride accumulation, Oil Red-O staining, and mRNA expression of $PPAR{\gamma}$, C/$EBP{\alpha}$, and leptin in a dose-dependent manner. Based upon these results, P80 from edible mushroom hinmogi shows the inhibitory activity on the differentiation of 3T3-L1 adipocytes. Therefore, it might be employed as a potential anti-obesity material.