• Journal of Animal Science and Technology
• /
• v.46 no.1
• /
• pp.23-30
• /
• 2004

The peroxisome proliferator-activated receptor $\gamma$(PPAR$\gamma$), a member of the steroid/thyroid nuclear hormone receptor suferfamily of ligand-activated transcription factor, is an important regulator of adipocyte gene expression and differentiation. In this studies, we report the identification, characterization, and expression of a Hanwoo PPAR$\gamma$ gene. The PPAR$\gamma$ cDNA sequence of the Hanwoo show strong conservation with the corresponding sequences reported in other species except of three amino acid sequences. The distribution of PPAR$\gamma$ mRNA in various tissues of Korean cattle aged 12 months were investigated using Northern Blot analysis. The highest expression was detected in adipose tissue, more lower expression was detected in colon, small intestine, kidney, lung, while expression was not detected in brain, heart. PPAR$\gamma$ expression was higher in adipose tissue of Korean cattle when aged 30 months than aged 12 months. These results indicated PPAR$\gamma$, regulator adipocyte gene expression and differentiation, related on adipose differentiation in Korean native cattle(HANWOO).

• Journal of Applied Biological Chemistry
• /
• v.60 no.1
• /
• pp.23-28
• /
• 2017

Amomum tsao-ko used as a traditional oriental herbal medicine, is indigenous to several Asia countries. In this study, we investigated anti-obesity activity of the ethanol extract of Amomum Taso-ko (A. tsao-ko). The ethanol extract of A. tsao-ko inhibited adipocyte differentiation using Oil Red O assay in 3T3-L1 cells. Inhibitory effect of the ethanol extract of A. tsao-ko on adipogenesis was modulated by down-regulation adipogenic transcriptional factor such as peroxisome proliferator-activated receptor ${\gamma}$ ($PPAR{\gamma}$), CCAAT-enhancer-binding protein ${\alpha}$ ($C/EBP{\alpha}$) and suppressed expression of fatty acid synthase, aP2, and resistin. We demonstrated that A. tsao-ko significantly inhibited adipogenesis and reduced $PPAR{\gamma}$ and $C/EBP{\alpha}$ expression in a dose-dependent manner. These results suggest that A. tsao-ko has an anti-obesity effect by inhibition of adipogenic transcription factor and adipocyte-specific genes in 3T3-L1 cells.

• Preventive Nutrition and Food Science
• /
• v.18 no.2
• /
• pp.85-91
• /
• 2013

Recent studies have shown that Rosa canina L. and tiliroside, the principal constituent of its seeds, exhibit anti-obesity and anti-diabetic activities via enhancement of fatty acid oxidation in the liver and skeletal muscle. However, the effects of rosehip, the fruit of this plant, extract (RHE), or tiliroside on lipid accumulation in adipocytes have not been analyzed. We investigated the effects of RHE and tiliroside on lipid accumulation and protein expression of key transcription factors in both in vitro and in vivo models. RHE and tiliroside inhibited lipid accumulation in a dose-dependent manner in 3T3-L1 cells. We also analyzed the inhibitory effect of RHE on white adipose tissue (WAT) in high-fat diet (HFD)-induced obesity mice model. Male C57BL/6J mice were fed HFD or HFD supplemented with 1% RHE (HFDRH) for 8 weeks. The HFDRH-fed group gained less body weight and had less visceral fat than the HFD-fed group. Liver weight was significantly lower in the HFDRH-fed group and total hepatic lipid and triglyceride (TG) content was also reduced. A significant reduction in the expression of peroxisome proliferator-activated receptor gamma (PPAR${\gamma}$) was observed in epididymal fat in the HFDRH-fed group, in comparison with controls, through Western blotting. These results suggest that downregulation of PPAR${\gamma}$ expression is involved, at least in part, in the suppressive effect of RHE on lipid accumulation in WAT.

• Asian Pacific Journal of Cancer Prevention
• /
• v.15 no.5
• /
• pp.2313-2318
• /
• 2014

Peroxisome proliferator-activated receptor gamma (PPAR-${\gamma}$), a ligand-dependent nuclear transcription factor, has been found to widely exist in tumor tissues and plays an important role in affecting tumor cell growth. In this study, we investigated the effect of PPAR-${\gamma}$ on aspects of the cervical cancer malignant phenotype, such as cell proliferation and apoptosis. Cell growth assay, Western blotting, Annexin V and flow cytometry analysis consistently showed that treatment with troglitazone (TGZ, a PPAR-${\gamma}$ agonist) led to dose-dependent inhibition of cervical cancer cell growth through apoptosis, whereas T0070907 (another PPAR-${\gamma}$ antagonist) had no effect on Hela cell proliferation and apoptosis. Furthermore, we also detected the protein expression of p53, p21 and Mdm2 to explain the underlying mechanism of PPAR-${\gamma}$ on cellular apoptosis. Our work, finally, demonstrated the existence of the TGZ-PPAR-${\gamma}$-p53 signaling pathway to be a critical regulator of cell apoptosis. These results suggested that PPAR-${\gamma}$ may be a potential therapeutic target for cervical cancer.

• Clinical and Experimental Reproductive Medicine
• /
• v.33 no.2
• /
• pp.105-113
• /
• 2006

Objective: To investigate the role of ERK and $PPAR{\gamma}$ on the $TGF-{\beta}1$ induced human endometrial stromal cell decidualization in vitro. Method: Endometrial stromal cells are cultured under the following condition: DMEM/F12 (10% FBS, 1 nM E2 and 100 nM P4). $TGF-{\beta}1$ (5 ng/ml), Rosiglitazone (50 nM), and PD98059 ($20{\mu}M$) were added according to experimental purposes. Trypan-Blue and hematocytometer were utilized to count cell number. Enzyme-linked immunosorbent assay (ELISA) and western blotting were utilized to detect proteins. Result: $TGF-{\beta}1$ inhibited proliferation of cultured human endometrial stromal cells and induced expression of PGE2 and prolactin. This effect was mediated by Smad and ERK activation. Administration of rosiglitazone, $PPAR{\gamma}$ agonist, prevented $TGF-{\beta}1$ effect on cell proliferation. Furthermore, Rosiglitazone inhibited $TGF-{\beta}1$ induced activation of ERK, consequently reduced PGE2 and prolactin production. Conclusion: $TGF-{\beta}1$ induced decidualization of endometrial stromal cell through Smad and ERK phosphorylation. $PPAR{\gamma}$ acts as a negative regulator of human ndometrial cell decidualization in vitro.

• Asian Pacific Journal of Cancer Prevention
• /
• v.16 no.6
• /
• pp.2333-2340
• /
• 2015

Background: Due to the strong inhibitory effects of $PPAR{\gamma}$ gene on the growth of cancer cells, the role of Pro12Ala polymorphism in $PPAR{\gamma}$ gene has been extensively investigated in cancer recently. However, the results were inconsistent according to cancer type. The aim of this study was to comprehensively evaluate the $PPAR{\gamma}$ Pro12Ala polymorphism and gastric cancer susceptibility. Materials and Methods: Search strategies were conducted in Pubmed, Medline (Ovid), Chinese biomedical database (CBM), China national knowledge infrastructure (CNKI), VIP, and Wanfang database, covering all publications, with the last search up to November 01, 2014. The strength of association between $PPAR{\gamma}$ Pro12Ala polymorphism and gastric cancer risk was assessed by OR with 95%CI. Results: A total of 546 cases and 827 controls in 5 case-control studies were included in this meta-analysis. The results indicated that the variant G allele carriers (CG+GG) had a 2.31 times higher risk for gastric cancer when compared with the homozygote CC (odds ratio (OR)=2.31, 95% confidence interval (CI)=1.67-3.21 for CG+GG vs. CC). In the subgroup analysis by ethnicity, significantly elevated risks were both found in Asians (OR=2.56, 95% CI=1.42-4.64) and Caucasians (OR=2.20, 95% CI=1.48-3.25). Similarly, in the subgroup analysis by H. pylori status, a significantly increased risk was identified in H. pylori (+) populations (OR=3.68, 95%CI=2.07-6.52), but not in H. pylori(-) populations (OR=1.17, 95%CI=0.58-2.39). Conclusions: This pooled analysis suggested that the $PPAR{\gamma}$ Pro12Ala polymorphism could be an independent predictive risk factor for gastric cancer especially in H. pylori infected populations in Asians and Caucasians. Nevertheless, prospectively designed cohort studies are needed to further investigate gene-gene and gene-environment interactions to confirm the combined effects of $PPAR{\gamma}$ Pro12Ala polymorphisms and H. pylori infection on gastric cancer risk.

• Asian Pacific Journal of Cancer Prevention
• /
• v.16 no.13
• /
• pp.5219-5223
• /
• 2015

Helicobacter pylori (H. pylori) infection as a serious problem in both adults and children can induce chronic gastritis, peptic ulcer disease (PUD), and possibly gastric cancer. The aim of the current study was to survey antibiotic resistance and also to determine influence of PPAR$\gamma$ polymorphism in patients with H. pylori infection. During an 11-month-period, 98 H. pylori isolates were collected from 104 biopsy specimens. In vitro susceptibility of H. pylori isolates to 4 antimicrobial agents metronidazole, clarithromycin, amoxicillin and tetracycline were assessed by quantitative method according to European Committee on Antimicrobial Susceptibility Testing (EUCAST) guideline. PPAR$\gamma$ polymorphism was determined using polymerase chain reaction-restriction fragment length polymorphism assay. The frequency of H. pylori infection in our study was 94.2%. In vitro susceptibility data showed that highest level of resistance was related to metronidazole (66.3%), and the majority of H. pylori isolates were highly susceptible to amoxicillin and tetracycline (94.9% and 96.9%, respectively). Genotypic frequencies were 25.5% for CC (Pro12Pro), 40.8% for GC (Pro12Ala) and 33.7% for GG (Ala12Ala). In our study, CG genotype had highest distributions among infected patients with H. pylori. The study suggests that the PPAR-$\gamma$ Pro12Ala polymorphism could be evaluated as a potential genetic marker for susceptibility to gastric cancer in the presence of H. pylori infection.

• Proceedings of the Korean Society of Toxicology Conference
• /
• 2001.05a
• /
• pp.167-167
• /
• 2001

Peroxisome proliferator-activated receptors(PPARs) are member of the neuclear hormone receptor superfamiliy of ligand-dependent transcription factors that heterodimerizes with the retinoid X receptor to function as a transcriptional regulator. They are divided into three subtypes(PPAR-$\alpha$, $\beta$ and ${\gamma}$).(omitted)

• Biomolecules & Therapeutics
• /
• v.18 no.1
• /
• pp.16-23
• /
• 2010

Adipocyte differentiation in human bone marrow mesenchymal stem cells (hBM-MSCs) is not as efficient as that in murine pre-adipocytes when induced by adipogenic agents including insulin, dexamethasone, and 3-isobutyl-1-methylxanthine (IDX condition). Therefore, the promotion of adipocyte differentiation in hBM-MSCs has been used as a cell culture model to evaluate insulin sensitivity for anti-diabetic drugs. In hBM-MSCs, $PPAR{\gamma}$ agonists or sulfonylurea anti-diabetic drugs have been added to IDX conditions to promote adipocyte differentiation. Here we show that troglitazone, a peroxisome proliferator-activated receptor-gamma ($PPAR{\gamma}$) agonist, significantly reduced the levels of anti-adipogenic $PGE_2$ in IDX-conditioned hBM-MSC culture supernatants when compared to $PGE_2$ levels in the absence of $PPAR{\gamma}$ agonist. However, there was no difference in the mRNA levels of cyclooxygenases (COXs) and the activities of COXs and prostaglandin synthases during adipocyte differentiation in hBM-MSCs with or without troglitazone. In hBM-MSCs, troglitazone significantly increased the mRNA level of 15-hydroxyprostaglandin dehydrogenase (HPGD) which can act to decrease $PGE_2$ levels in culture. These results suggest that the role of $PPAR{\gamma}$ activation in promoting adipocyte differentiation in hBM-MSCs is to reduce anti-adipogenic $PGE_2$ levels through the up-regulation of HPGD expression.

• Journal of Life Science
• /
• v.21 no.5
• /
• pp.647-655
• /
• 2011

The neurotoxicity of aggregated amyloid ${\beta}$ ($A{\beta}$) has been implicated as a critical cause in the pathogenesis of Alzheimer's disease (AD). It can cause neurotoxicity in AD by evoking a cascade of apoptosis to neuron. Here, we investigated the neuroprotective effects of cilostazol, which acts as a phosphodiesterase III inhibitor, on $A{\beta}_{25-35}$-induced cytotoxicity in mouse neuronal cells and cognitive decline in the C57BL/6J AD mouse model via peroxisome proliferator-activated receptor (PPAR)-${\gamma}$ activation. $A{\beta}_{25-35}$ significantly reduced cell viability and increased the number of apoptotic-like cells. Cilostazol treatment recovered cells from $A{\beta}$-induced cell death as well as rosiglitazone, a PPAR-${\gamma}$ activator. These effects were suppressed by GW9662, an antagonist of PPAR-${\gamma}$ activity, indicative of a PPAR-${\gamma}$-mediated signaling. In addition, cilostazol and rosiglitazone also restored PPAR-${\gamma}$ activity levels that had been altered as a result of $A{\beta}_{25-35}$ treatment, which were antagonized by GW9662. Furthermore, cilostazol also markedly decreased the number of apoptotic-like cells and decreased the Bax/Bcl-2 ratio. Intracerebroventricular injection of $A{\beta}_{25-35}$ in C57BL/6J mice resulted in impaired cognitive function. Oral administration of cilostazol (20 mg/kg) for 2 weeks before $A{\beta}_{25-35}$ injection and once a day for 4 weeks post-surgery almost completely prevented the $A{\beta}_{25-35}$-induced cognitive deficits, as did rosiglitazone. Taken together, our findings suggest that cilostazol could attenuate $A{\beta}_{25-35}$-induced neuronal cell injury and apoptosis as well as promote the survival of neuronal cells, subsequently improving cognitive decline in AD, partly because of PPAR-${\gamma}$ activation. The phosphodiesterase III inhibitor cilostazol may be the basis of a novel strategy for the therapy of AD.