• Nutrition Research and Practice
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• 제7권6호
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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.

• 한방안이비인후피부과학회지
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• 제23권2호
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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-$\gamma$.

• Bulletin of the Korean Chemical Society
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• 제32권8호
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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.

• 대한한방소아과학회지
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• 제21권1호
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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.

• Yonsei Medical Journal
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• 제59권9호
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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.

• 생명과학회지
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• 제22권8호
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• pp.1052-1056
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• 2012

미역(Undaria pinnatifada)은 낮은 칼로리 및 요오드의 원료로써 천연체중조절식품으로 알려져 있다. 미역이 체중조절식품으로 알려져 있음에도 불구하고, 지방세포 분화 및 지방축적에 관한 저해 기작은 연구가 미비하다. 본 연구에서는 3T3-L1에서 지방세포로 분화가 일어나는 단계에서 미역에탄올추출물의 효과 및 기작을 확인하였다. 미역에탄올추출물의 독성과 지방축적저해효과는 MTT assay, Oil red O staining, RT-PCR과 western blot으로 분석하였다. 미역에탄올추출물은 50 ${\mu}g/ml$의 농도에서 독성을 띄지 않았다. 3T3-L1의 분화 및 지방세포에서 triglyceride축적과정동안 50 ${\mu}g/ml$의 미역에탄올추출물을 처리하였으며, 미역에탄올추출물은 지방세포에서 triglyceride의 축적을 40% 감소시켰다. 지방세포 특이적 단백질인 Peroxisome proliferator activated receptor ${\gamma}$ ($PPAR{\gamma}$), leptin과 Hormone sensitive lipase (HSL)의 발현은 RT-PCR과 western blot으로 확인하였다. $PPAR{\gamma}$의 과발현은 지방세포의 분화를 촉진시킨다. 또한 지방세포 크기의 증가와 세포 내 triglyceride의 함량에 따라 leptin은 세포 외로 분비된다. 그러므로 $PPAR{\gamma}$와 leptin은 비만의 지표로 사용된다. 첨가한 미역에탄올추출물의 농도가 높아질수록 $PPAR{\gamma}$와 leptin의 발현이 억제되었다. 이상의 결과를 통하여, 미역의 에탄올 추출물은 지방전구세포의 분화를 억제시키며, 지방세포 내 triglyceride의 축적을 저해하는 것으로 판단된다.

• 대한약학회:학술대회논문집
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• 대한약학회 2003년도 Proceedings of the Convention of the Pharmaceutical Society of Korea Vol.2-2
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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)

• 대한한방내과학회지
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• 제28권4호
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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.

• 한국식품영양과학회지
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• 제41권2호
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• pp.161-167
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• 2012

본 연구에서는 3T3-L1 지방전구세포를 이용하여 용아초 에틸아세테이트 추출물의 항비만 활성을 확인하고자 하였다. 용아초 에틸아세테이트 추출물에 의한 지방세포 분화 및 adipogenesis 저해 활성을 확인하기 위해 추출물을 3T3-L1 지방전구세포에 분화를 유도하면서 농도별(50, 100 ${\mu}g/mL$)로 처리하였고, 그 결과 용아초 에틸아세테이트 추출물은 지방세포의 분화를 억제시켰다. 이 같은 활성에 대한 기전을 확인하기 위해 PPAR${\gamma}$ 전사활성과 지방세포 분화에 관여하는 유전자들의 활성을 확인해 보았다. 실험 결과 용아초 에틸아세테이트 추출물은 PPAR${\gamma}$ 전사 활성을 억제시켰고 PPAR${\gamma}$ 및 C/EBP${\alpha}$의 mRNA 발현을 농도 의존적으로 감소시켰으며 지방세포 분화에 관여하는 adipokine들의 발현을 조절하는 것으로 나타났다. 따라서 용아초 에틸아세테이트 추출물의 항비만 효과는 지방 생성의 주요 전사인자인 PPAR${\gamma}$와 C/EBP${\alpha}$의 유전자 발현조절을 통해 지방 분화 억제 및 지방 축적을 효과적으로 감소시키는 것으로 보이며, 효과가 있는 농도가 100 ${\mu}g/mL$로 천연물질로써 비교적 낮은 농도에서 효과가 나타나는 것으로 보아 항비만 소재로의 개발 가능성이 있을 것으로 사료된다.

• Food Science and Biotechnology
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• 제17권2호
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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.