• 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.

• Journal of Physiology & Pathology in Korean Medicine
• /
• v.20 no.2
• /
• pp.383-387
• /
• 2006

To investigate the effect of GyeongshinhaeGihwan 1(GGT1) frequently used as an anti-obesity herbal medicine in oriental medicine on the expression of obesity-related genes, we measured the changes in mRNA levels of these genes by GGT1 in human growth hormone transgenic (hGHTg) obese female rats, and these effects by GGT1 were compared with those of reductil (RD), an anti-obesity drug approved by FDA. Rats received once daily oral administrations of autoclaved water, RD, or GGT1 for 8 weeks. At the end of study, rats were sacrificed and tissues were harvested. Total RNA from adipose tissue, liver and kidney was prepared and the mRNA levels for LPL (lipoprotein lipase), $PPAR{\gamma}$ (peroxisome proliferator activated receptor-gamma), $PPAR{\delta}$ (peroxisome proliferator activated receptor-delta), leptin, $TNF{\alpha}$ (tumor necrosis factor-alpha), and internal standard G3PDH (glyceraldehyde-3-phosphate dehydrogenase) were analyzed by RT-PCR. Compared with control group, $PPAR{\gamma}$ mRNA levels of liver and kidney were decreased in both RD and GGT1 groups, and the effects were more prominent in GGT1 group than in RD group, suggesting that GGT1 is effective in the inhibition of lipid storage by decreasing the $PPAR{\gamma}$ expression. $PPAR{\delta}$ mRNA levels of adipose tissue were increased by RD and GGT1 compared with DW, and the magnitude of increase were higher in GGT1 group than in RD group, indicating that GGT1 stimulates fatty acid oxidation and energy metabolism by activating $PPAR{\delta}$ expression. GGT1 group had higher concentrations of serum leptin, a well-known inhibitor of appetite, than control and RD groups. However, The mRNA levels of leptin, LPL, and $TNF{\alpha}$ were not changed by GGT1. These results indicate that GGT1 can prevent obesity in hGHTg obese female rats by down-regulating and up-regulating the mRNA expression of $PPAR{\gamma}$ and $PPAR{\delta}$, respectively, and that this anti-obesity effects were more pronounced in GGT1 group compared with RD group. In addition, GGT1 seems to inhibit obesity by increasing the circulating leptin levels.

• Asian-Australasian Journal of Animal Sciences
• /
• v.29 no.9
• /
• pp.1256-1264
• /
• 2016

Adrenergic, alpha-1B-, receptor (ADRA1B) and peroxisome proliferator-activated receptor gamma, coactivator 1 beta (PPARGC1B) genes are involved in regulation of hen ovarian development. In this study, these two genes were investigated as possible molecular markers associated with hen-housed egg production, egg weight (EW) and body weight in Chinese Dagu hens. Samples were analyzed using the polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP) technique, followed by sequencing analysis. Two novel single nucleotide polymorphisms (SNPs) were identified within the candidate genes. Among them, an A/G transition at base position 1915 in exon 2 of ADRA1B gene and a T/C mutation at base position 6146 in the 3'- untranslated region (UTR) of PPARGC1B gene were found to be polymorphic and named SNP A1915G and T6146C, respectively. The SNP A1915G (ADRA1B) leads to a non-synonymous substitution (aspartic acid 489-to-glycine). The 360 birds from the Dagu population were divided into genotypes AA and AG, allele A was found to be present at a higher frequency. Furthermore, the AG genotype correlated with significantly higher hen-housed egg production (HHEP) at 30, 43, 57, and 66 wks of age and with a higher EW at 30 and 43 wks (p<0.05). For the SNP T6146C (PPARGC1B), the hens were typed into TT and TC genotypes, with the T allele shown to be dominant. The TC genotype was also markedly correlated with higher HHEP at 57 and 66 wks of age and EW at 30 and 43 wks (p<0.05). Moreover, four haplotypes were reconstructed based on these two SNPs, with the AGTC haplotype found to be associated with the highest HHEP at 30 to 66 wks of age and with higher EW at 30 and 43 wks (p<0.05). Collectively, the two SNPs identified in this study might be used as potential genetic molecular markers favorable in the improvement of egg productivity in chicken breeding.

• Journal of Nutrition and Health
• /
• v.40 no.3
• /
• pp.221-228
• /
• 2007

We determined the effects of dietary manipulations on messenger RNA of peroxisome proliferators activated receptor isoforms (i.e., PPAR ${\alpha},\;{\beta}/{\delta},\;{\gamma}$) in red vastus lateralis muscle of rats. Total 16 male Sprague-Dawley rats were used, and animals were divided into one of two dietary conditions: either chow diet group (CHOW; n=8) in which animals were 134 with standard rodent chow (61.8% carbohydrate, 15.7% fat, 22.5% protein) or high fat diet group (FAT n=8) in which animals were fed 24.3% carbohydrate, 52.8% fat, 22.9% protein. At the end of the 8 weeks of experimental period, red vastus lateralis muscle was dissected out from all animals, and PPAR ${\alpha},\;{\beta}/{\delta},\;{\gamma}$ mRNA expression was determined. There was no significant difference in body mass (BM) between CHOW and FAT. As expected, blood glucose and free fatty acid (FFA) concentration was higher in FAT than CHOW (p<0.05), and lactate concentration was significantly lower in FAT compared to CHOW (p<0.05). Insulin concentration tended to higher in FAT than CHOW ($67.2{\pm}21.9\;vs.\;27.0{\pm}5.2$ pmol/L), but it did not reach to the statistical significance. Gene expression of PPAR ${\alpha}$ was not significantly different between CHOW and FAT. It was not also significantly different in PPAR ${\beta}/{\delta}$. Interestingly, expression of mRNA in PPAR ${\gamma}$ however, was markedly depressed in FAT compared to CHOW (approximately 3 fold higher in CHOW; p<0.05). Results obtained from present study implies that PPAR ${\gamma}$ (as compensatory function of PPAR ${\alpha}$ is expressed) possibly exerts another major tuning roles in fatty acid transport, utilization, as well as biosynthesis in skeletal muscle cells. The situations and conditions that can be postulated for this implication need to be further examined.

• Development and Reproduction
• /
• v.13 no.4
• /
• pp.249-256
• /
• 2009

The estrogen receptor-related receptors (ERRs) are a group of nuclear receptor superfamily of transcription factors. ERRs and estrogen receptors (ERs) have overlapping affinities for coactivators and DNA binding sites, but differ markedly in ligand binding and activation. The three mammalian ERR genes have been implicated in diverse physiological processes ranging from placental development to maintenance of bone density, whereas the molecular diversity, function, and regulation of ERRs in non-mammalian species are not well understood. In the present study, to investigate the involvement of ERR in transcription and embryogenesis in marine invertebrates, a cDNA encoding ERR (SnERR) was cloned from the gonad in Strongylocentrotus nudus, by polymerase chain reaction (PCR). The amino acid sequence of SnERR showed high homology with that of S. purpuratus (91%). A phylogenetic tree clearly showed that SnERR is a member of the ERR family and clustered in echinodermata group as supported by a high bootstrap value. We examined gene expression of SnERR during embryonic development of S. nudus using real-time PCR. During the embryonic development, the mRNA of ERR was significantly high levels in early development stages (4~64 cell) and larval stages. The SnERR slightly activated transcription through the classical estrogen response elements (EREs) in the presence of genistein. In addition, peroxisome proliferator-activated receptor $\gamma$ coactivator (PGC)-$1\alpha$ knwon as a coactivator of ERR enhanced the snERR-mediated transactivation, suggesting that the PGC-$1\alpha$ is a coactivator of SnERR.

• Journal of Life Science
• /
• v.22 no.8
• /
• pp.1052-1056
• /
• 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.

• Journal of Applied Biological Chemistry
• /
• v.62 no.4
• /
• pp.417-424
• /
• 2019

The aim of this study is to investigate the effect of Lespedeza maximowiczii var. tricolor Nakai (LMTN) on glucose metabolism. LMTN extract significantly enhanced the glucose uptake and lipid accumulation in 3T3-L1 adipocytes compared with control. Also, LMTN extract in 3T3-L1 adipocytes significantly increased the protein expression of peroxisome proliferator-activated receptor (PPAR)γ, insulin receptor substrate-1, and glucose transporter (GLUT)4. The regulatory effect on glucose uptake or insulin signal transduction of LMTM extract was lower than troglitazone or pinitol such as the positive control, but increased PPARγ activation. Additionally, LMTM extract has an insulin-mimetic effect. In db/db mice, LMTN extract (250 mg/kg BW) significantly reduced water and food intake, blood glucose, and level of plasma triglyceride and total cholesterol. Furthermore, the expression of PPARã and GLUT4 mRNA in adipose or muscle tissue effectively was increased by oral treatment of LMTN extract. Thus, our results suggest that LMTN extract improves the glucose metabolism through PPARγ and insulin-mimetic effect in 3T3-L1 adipocytes and db/db mice.

• Korean Journal of Food Science and Technology
• /
• v.47 no.4
• /
• pp.499-503
• /
• 2015

We investigated the anti-obesity effects of ethanolic extract (ID1216) of Polygonatum sibiricum rhizome and its potential underlying mechanism in an animal model. ID1216 treatment decreased body weight gain and white adipose tissue weight in the prevention study. The mRNA levels of sirtuin-1 (SIRT1), peroxisome proliferator-activated receptor ${\gamma}$ coactivator-$1{\alpha}$ ($PGC1{\alpha}$), and peroxisome proliferator-activated receptor ${\alpha}$ ($PPAR{\alpha}$) significantly increased in the epididymal white adipose tissue of ID1216-administered mice. The stimulation effects of ID1216 on these gene expressions were also observed in a cell-based assay using differentiated 3T3-L1 adipocytes. In addition, similar to orlistat, ID1216 treatment improved weight gain and reduced epididymal fat in the treatment model. These results suggest that ID1216 has potential as an anti-obesity agent by modulating the expression of genes related to thermogenesis, lipid metabolism and fatty acid oxidation.

• 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.

• Korean Journal of Plant Resources
• /
• v.28 no.5
• /
• pp.635-640
• /
• 2015

Nonalcoholic fatty liver disease (NAFLD) is a kind of liver inflammation caused by an accumulation of fat in the liver. Patients with NAFLD have an increased risk to develop liver fibrosis, which leads to cirrhosis. To investigate hepatoprotective effects of Agrimonia eupatoria L (A. eupatoria), oleic acid-induced NAFLD in HepG2 cells was used and A. eupatoria was fractionated with ethanol (EtOH), n-hexane, dichloromethane (CH₂Cl₂), ethyl acetate (EtOAc), n-butanol (BuOH), and H₂O. Cells treated with the EtOAc fraction showed the highest lipid accumulation inhibiting effect. A. eupatoria also suppressed triglyceride accumulation and inhibited expression of lipid marker gene, such as a peroxisome proliferator activated receptor γ (PPAR-γ). Moreover, another marker, mRNA expression level of peroxisome proliferator activated receptor α (PPAR-α) was significantly increased by in a dose-dependent manner. These results suggest that A. eupatoria is a potent agent for the treatment of NAFLD.