• 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)

• 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?

• 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.

• 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.

• 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.

• 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.

• Asian-Australasian Journal of Animal Sciences
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• v.20 no.3
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• pp.340-350
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• 2007

The objective of this study was to determine whether peroxisome proliferator-activated receptor ${\gamma}$(PPAR${\gamma}$ is involved in the regulation of weaning to estrus of primiparous sows. Twelve sows composed of 6 groups of 2 full-sibs in a similar age (325.2 d), body weight (BW; 152.4 kg) and backfat thickness (BFT; 27.0 mm) at start of lactation, were allocated to accept 31 MJ (restricted group, R-group) or 53 MJ (control group, C-group) DE/d treatment, respectively. The experimental results indicated that the low energy intake resulted in excessive losses of BW and BFT during lactation in R-group sows, which may be related to decrease of serum 15-deoxy-${\Delta}^{12,14}$-prostaglandin $J_2$ (15d-$PGJ_2$), a ligand of PPAR${\gamma}$ The obvious peak and the frequency of LH, FSH and estradiol ($E_2$) were only observed in C-group sows. Except for $E_2$ at d 1 and 2, serum FSH, LH and $E_2$ concentrations in R-group were lower than those in C-group sows after weaning. However, the serum progesterone ($P_4$) level in R-group sows was always more than that in C-group. The expression abundances of PPAR${\gamma}$and GnRH receptor (GnRH-R) in pituitary, FSH receptor (FSH-R), LH receptor (LH-R), estrogen receptor (ES-R) and aromatase in ovary of anestrous sows were lower than those of estrous sows. Neither the BFT nor the BW was associated with the mRNA abundance of PPAR${\gamma}$in hypothalamus during lactation. Expressions of PPAR${\gamma}$in pituitary and ovary were affected evidently by the BFT changes and only by the loss of BW of sows during and after lactation. Furthermore, PPAR${\gamma}$mRNA level in ovary was significantly related to the expression abundances of GnRH-R, FSH-R, ES-R and aromatase, and GnRH-R was obviously associated with PPAR${\gamma}$expression in pituitary. However, PPAR${\gamma}$expression in hypothalamus likely has no effects on these genes expression and no obvious difference for all sows. Not serum $E_2$ or $P_4$ alone but the ratios of $E_2$ to $P_4$ and 15d-$PGJ_2$ to $P_4$, and serum FSH and LH were evidently related to PPAR${\gamma}$expression in pituitary and ovary. It is concluded that PPAR${\gamma}$is associated with body conditions, reproduction hormones and their receptor expression, which affected the functions of pituitary and ovary and ultimately the estrus after weaning of primiparous sows.

• Clinical and Experimental Reproductive Medicine
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• v.40 no.2
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• pp.67-75
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• 2013

Objective: To investigate the effect of peroxisome proliferator activated receptor ${\gamma}$(PPAR${\gamma}$) agonist on the cell proliferation properties and expression of human telomerase reverse transcriptase (hTERT) and aromatase in cultured endometrial stromal cell (ESC) from patients with endometriosis. Methods: Human endometrial tissues were obtained from women with endometriosis and healthy women (controls) using endometrial biopsy. Isolated ESCs were cultured and the cell proliferation was measured by 3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide assay and expression of hTERT, aromatase, and cyclooxygenase (COX)-2 by western blotting according to the addition of rosiglitazone (PPAR${\gamma}$ agonist). Results: We demonstrate that the cultured ESCs of endometriosis showed hTERT protein overexpression and increased cellular proliferation, which was inhibited by rosiglitazone, in a dose-dependent manner. At the same time, PPAR${\gamma}$ agonist also inhibited aromatase and COX-2 expression, resulting in decreased prostaglandin $E_2$ production in the ESCs of endometriosis. Conclusion: This study suggests that PPAR${\gamma}$ agonist plays an inhibitory role in the proliferative properties of eutopic endometrium with endometriosis by down-regulation of hTERT and COX-2 expression; this could be a new treatment target for endometriosis.

• Food Science and Biotechnology
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• v.17 no.6
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• pp.1146-1150
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• 2008

Peroxisome proliferator-activated receptor-gamma ($PPAR_{\gamma}$), a member of the nuclear receptor of ligand-activated transcription factors, plays a key role in lipid and glucose metabolism or adipocytes differentiation. A lignan compound was isolated from mace (the aril of Myristica fragrans Houtt.) as a $PPAR_{\gamma}$ ligand, which was identified as fragrin A or 2-(4-allyl-2,6-dimethoxyphenoxy)-1-(4-hydroxy-3-methoxyphenyl)-propane. To ascertain whether fragrin A has $PPAR_{\gamma}$ ligand-binding activity, it was performed that GAL-4/$PPAR_{\gamma}$ transactivation assay. $PPAR_{\gamma}$ ligand-binding activity of fragrin A increased 4.7, 6.6, and 7.3-fold at 3, 5, and $10{\mu}M$, respectively, when compared with a vehicle control. Fragrin A also enhanced adipocytes differentiation and increased the expression of $PPAR_{\gamma}$ target genes such as adipocytes fatty acid-binding protein (aP2), lipoprotein lipase (LPL), and phosphoenol pyruvate carboxykinase (PEPCK). Furthermore, it significantly increased the expression level of glucose transporter 4 (GLUT4). These results indicate that fragrin A can be developed as a $PPAR_{\gamma}$ agonist for the improvement of insulin resistance associated with type 2 diabetes.