• Biomedical Science Letters
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• v.14 no.3
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• pp.139-146
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• 2008

The peroxisome proliferator-activated receptor ${\gamma}$ $(PPAR{\gamma})$ plays a central role in adipogenesis and lipid storage. The $(PPAR{\gamma})$ ligands, thiazolidinediones (TZDs), enhance in vitro adipogenesis in several cell types, but the role of the TZDs on in vivo adipogenesis is still poorly understood. To investigate how $PPAR{\gamma}$ ligand troglitazone regulates adipogenesis in female mice, we examined the effects of the troglitazone on adipose tissue mass, morphological changes of adipocytes, and the expression of $PPAR{\gamma}$ target and adipocyte-specific genes in low fat diet-fed female C57BL/6 mice. Administration of troglitazone for 13 weeks did not change body and total white adipose tissue weights compared with control mice. Troglitazone treatment also did not cause a significant decrease in the average size of adipocytes in parametrial adipose tissue although it is reported to increase the number of small adipocytes in male animals. Troglitazone did not affect the mRNA expression of $PPAR{\gamma}$ and its target genes as well as adipocyte-specific genes in parametrial adipose tissue. These results suggest that $PPAR{\gamma}$ does not seem to be associated with adipogenesis in females with functioning ovaries and that its inability to induce adipogenesis may be due to sex-related factors.

• 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.

• 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)

• BMB Reports
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• v.36 no.2
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• pp.207-213
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• 2003

Peroxisome proliferator-activated receptors (PPARs) are orphan nuclear hormone receptors that are known to control the expression of genes that are involved in lipid homeostasis and energy balance. PPARs activate gene transcription in response to a variety of compounds, including hypolipidemic drugs. Most of these compounds have high affinity to the ligand-binding domain (LBD) of PPARs and cause a conformational change within PPARs. As a result, the receptor is converted to an activated mode that promotes the recruitment fo co-activators such as the steroid receptor co-activator-1 (SRC-1). Based on the activation mechanism of PPARs (the ligand binding to $PPAR{\gamma}$ induces interactions of the receptor with transcriptional co-activators), we performed Western blot and ELISA. These showed that the indomethacin, a $PPAR{\gamma}$ ligand, increased the binding between $PPAR{\gamma}$ and SRC-1 in a ligand dose-dependent manner. These results suggested that the in vitro conformational change of $PPAR{\gamma}$ by ligands was also induced, and increased the levels of the ligand-dependent interaction with SRC-1. Collectively, we developed a novel and useful ELISA system for the mass screening of $PPAR{\gamma}$ ligands. This screening system (based on the interaction between $PPAR{\gamma}$ and SRC-1) may be a promising system in the development of drugs for metabolic disorders.

• Molecules and Cells
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• v.24 no.2
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• pp.167-176
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• 2007

Peroxisome proliferator-activated receptor-gamma ($PPAR{\gamma}$) is expressed at very high levels in the gastrointestinal epithelium. Many of the functions of $PPAR{\gamma}$ in gastrointestinal epithelial cells have been elucidated in recent years, and a pattern is emerging which suggests that this receptor plays an important role in gastrointestinal physiology. There is also strong evidence that $PPAR{\gamma}$ is a colon cancer suppressor in pre-clinical rodent models of sporadic colon cancer, and there is considerable interest in exploitation of $PPAR{\gamma}$ agonists as prophylactic or chemopreventive agents in colon cancer. Studies in mice and in human colon cancer cell lines suggest several mechanisms that might account for the tumor suppressive effects of $PPAR{\gamma}$ agonists, although it is not in all cases clear whether these effects are altogether mediated by $PPAR{\gamma}$. Conversely, several reports suggest that $PPAR{\gamma}$ agonists may promote colon cancer under certain circumstances. This possibility warrants considerable attention since several million individuals with type II diabetes are currently taking $PPAR{\gamma}$ agonists. This review will focus on recent data related to four critical questions: what is the physiological function of $PPAR{\gamma}$ in gastrointestinal epithelial cells; how does $PPAR{\gamma}$ suppress colon carcinogenesis; is $PPAR{\gamma}$ a tumor promoter; and what is the future of $PPAR{\gamma}$ in colon cancer prevention?

• Biomedical Science Letters
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• v.10 no.2
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• pp.137-142
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• 2004

The peroxisome proliferator-activated receptor $\gamma$ (PPAR${\gamma}$) is the molecular target for a class of drugs, the antidiabetic thiazolidnediones (TZDs). The heterodimer of PPAR${\gamma}$ with retinoid X receptor (RXR) plays a central role in the regulation of adipogenesis and insulin sensitization. We synthesized two chemicals, DANA87 and DANA88, sharing structural characteristics with TZDs. Given this structural similarity, it was hypothesized that DANA87 and DANA88 may act as PPAR$\gamma$ ligands. In transient transfection assays, DANA87 and DANA88 caused slight increases in the endogenous expression of a luciferase reporter gene containing the PPAR responsive element in 3T3-L1 preadipocytes. However, DANA87 and DANA88 significantly inhibited troglitazone-induced reporter gene activation when cells were treated with a combination of DANA87 or DANA 88 and troglitazone, one of the TZDs that activate PPAR$\gamma$. These results suggest that DANA87 and DANA88 are not only weak agonists of PPAR${\gamma}$ transactivation, but also competitively antagonize troglitazone-induced PPAR$\gamma$ reporter activity.

• Journal of Animal Science and Technology
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• v.57 no.11
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• pp.40.1-40.7
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• 2015

Background: Activation of peroxisome proliferator activated receptor gamma ($PPAR{\gamma}$) in the alveolar macrophages (AM) by selective synthetic $PPAR{\gamma}$ ligands, improves the ability of the cells to resolve inflammation. In birds, respiratory macrophages are known as free avian respiratory macrophages (FARM) and show distinct functional differences from AM. The effects of treating FARM with $PPAR{\gamma}$ ligands are unclear. Methods: FARM were harvested by lavage of chicken respiratory tract and their morphology assessed at microscopic level. The effects of $PPAR{\gamma}$ agonists on the FARM in vitro viability, phagocytic capacity and proinflammatory cytokine (TNF-${\alpha}$) production were assessed. Results: FARM had eccentric nucleus and plasma membrane ruffled with filopodial extensions. Ultrastructurally, numerous vesicular bodies presumed to be lysosomes were present. FARM treated with troglitazone, a selective $PPAR{\gamma}$ agonist, had similar in vitro viability with untreated FARM. However, treated FARM co-cultured with polystyrene particles, internalized more particles with a mean volume density of 41 % compared to that of untreated FARM of 21 %. Further, treated FARM significantly decreased LPS-induced TNF-${\alpha}$ production in a dose dependent manner. Conclusion: Results from this study show that $PPAR{\gamma}$ synthetic ligands enhance phagocytic ability of FARM. Further the ligands attenuate production of proinflammatory cytokines in the FARM, suggesting potential therapeutic application of $PPAR{\gamma}$ ligands in the management of respiratory inflammatory disorders in the poultry industry.

• 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.

• Bulletin of the Korean Chemical Society
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• v.33 no.5
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• pp.1475-1479
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• 2012

Human peroxisome proliferator-activated receptor gamma ($hPPAR{\gamma}$) has been implicated in numerous pathologies, including obesity, diabetes, and cancer. In this study, we verified that amentoflavone is an agonist of $hPPAR{\gamma}$ and probed the molecular basis of its action. It was demonstrated that amentoflavone bound $hPPAR{\gamma}$ with high (picomolar) affinity and increased the binding between $hPPAR{\gamma}$ and steroid receptor coactivator-1 (SRC-1) by approximately 4-fold. Based on a docking study, for the first time, we propose a model of amentoflavone and $hPPAR{\gamma}$ binding in which amentoflavone forms three hydrogen bonds with the side chains of His323, Tyr327, and Arg280 in $hPPAR{\gamma}$ and participates in two hydrophobic interactions.

• 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.