• Biomolecules & Therapeutics
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• 제18권1호
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• pp.77-82
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• 2010

Peroxisome proliferator-activated receptor $\gamma$ (PPAR${\gamma}$) is a ligand-activated transcription factor that is used as a target for anti-diabetic drug development. In a search for novel PPAR${\gamma}$ agonists, the $\beta$-carboxyethyl-rhodanine derivative SP1818 was identified. We report here the characteristics of SP1818 as a selective PPAR${\gamma}$ agonist. In transactivation assays, SP1818 selectively activated PPAR${\gamma}$, but the degree of PPAR${\gamma}$ stimulation was less than with $1{\mu}M$ rosiglitazone. SP1818 also stimulated glucose uptake in a concentration-dependent manner. The adipocyte differentiation markers adiponectin, scavenger receptor CD36 and aP2 were weakly induced by treatment with SP1818, and TRAP220 subunit was specifically recruited into PPAR${\gamma}$ activated by rosiglitazone but not PPAR${\gamma}$ activated by SP1818.

• Biomolecules & Therapeutics
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• 제18권1호
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• pp.16-23
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• 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.

• Asian Pacific Journal of Cancer Prevention
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• 제15권5호
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• pp.2313-2318
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• 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.

• Biomedical Science Letters
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• 제20권2호
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• pp.62-69
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• 2014

Previous our study demonstrated that ailanthoidol (3-deformylated 2-arylbenzo[b]furan), a neolignan from Zanthoxylum ailanthoides or Salvia miltiorrhiza Bunge, is a novel anti-inflammatory agent. In this investigation, we examined the anti-adipogenic effect of ailanthoidol. Our data showed that ailanthoidol suppressed lipid droplet formation and adipocyte differentiation in 3T3-L1 cells. Treatment of the 3T3-L1 adipocytes with ailanthoidol resulted in an attenuation of the releases of leptin and interleukin-6. The expression of peroxisome proliferator-activated receptor $(PPAR){\gamma}$ and CCAAT/enhancer-binding protein $(C/EBP){\alpha}$, the central transcriptional regulators of adipogenesis, was decreased by treatment with ailanthoidol. Additionally, ailanthoidol treatment increased the phosphorylation levels of 5' adenosine monophosphate-activated protein kinase. These results suggest that ailanthoidol effectively suppresses adipogenesis and that it exerts its role mainly through the significant down-regulation of $PPAR{\gamma}$ and $C/EBP{\alpha}$ expression. Our findings provide important insights into the mechanisms underlying the anti-adipogenic activity of ailanthoidol.

• BMB Reports
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• 제42권5호
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• pp.281-285
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• 2009

Peroxisomes play an important role in cellular defense systems and generate secondary messengers for cellular communication. Saccharomyces cerevisiae containing oleate-induced peroxisomes were subjected to buffer-soluble extraction and two chromatographic procedures, and a protein with antifungal activity was isolated. The results of MALDI-TOF analysis identified the isolated protein as peroxisomal 3-ketoacyl-CoA thiolase (ScFox3). Purified yeast ScFox3 exhibited thiolase activity that catalyzed the thiolytic cleavage of 3-ketoacyl-CoA to acetyl-CoA and acyl-CoA. ScFox3 protein inhibited various pathogenic fungal strains, with the exception of Aspergillus flavus. Using ScFox3-GFP and PTS2 signal-truncated ScFox3M-GFP, we showed that only ScFox3-GFP, with an intact PTS2 peroxisome signal sequence, was able to translocate into peroxisomes. Yeast ScFox3 is a natural antifungal agent found in peroxisomes.

• Preventive Nutrition and Food Science
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• 제11권4호
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• pp.285-288
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• 2006

The anti-adipogenic effect of dongchimi nano juice prepared using a nano-filtering process was investigated by measuring leptin and glycerol levels and the expression of a peroxisome proliferator-activated $receptor-\gamma\;(PPAR\gamma)$ gene as indicators of lipid accumulation or lipolysis. Red pepper powder, seeds of red pepper, garlic, and ginger were added in the preparation of dongchimi. Dongchimi was fermented to reach the optimal fermentation period, followed by nano-filtration in the range of $0.0005\sim0.1\;{\mu}m$. The lactic acid bacteria of dongchimi nano juice were removed completely by a nano-filtering process. Treatment of dongchimi nano juice induced glycerol release in the 3T3-L1 adipocytes and decreased the mRNA expression level of $PPAR\gamma$. These results suggested that dongchimi nano juice may enhance lipolysis and modulate adipogenesis in 3T3-L1 cells.

• Journal of Nutrition and Health
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• 제26권7호
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• pp.887-898
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• 1993

In order to determine the effect of iron depletion and subsequent supplementation on the muscle capacity for peroxisomal (PO) and mitochondrial(MO) $\beta$-oxidation during high fat feeding, weanling rats were fed a 44% (HF) or 2.5% (LF) fat diet with (+Fe) or without (-Fe) iron for 6 or 9 weeks. After 1 week rats fed HF+Fe or HF-Fe had 50-100% more PO and MO in heart, soleus, psoas and gastrocnemius than did rats fed low fat, but after 3 weeks rats fed HF-Fe had lower muscle PO and MO. In muscles of iron depleted rats PO and MO were not increased by supplementation with iron for 3 weeks. After 6 weeks MO and PO in skeletal muscles of rats fed HF+Fe were lower than after 3 weeks. It is concluded that adequate iron is necessary for miaximum response of muscle PO and MO to high fat feeding. However, after 6 weeks both PO and MO have returned to levels similar to those of rats fed low fat diets, hence, the elevated catalase activities seen at this time do not reflect peroxisomal $\beta$-oxidation.

• Nutrition Research and Practice
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• 제6권4호
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• pp.286-293
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• 2012

Resveratrol (3,4,5-trihydroxy-trans-stilbene), a phytoalexin found in grape skin, grape products, and peanuts as well as red wine, has been reported to have various biological and pharmacological properties. The purpose of this study was to investigate the anti-obesity effect of resveratrol-amplified grape skin extracts on adipocytes. The anti-obesity effects of grape skin extracts were investigated by measuring proliferation and differentiation in 3T3-L1 cells. The effect of grape skin ethanol extracts on cell proliferation was detected by the MTS assay. The morphological changes and degree of adipogenesis of preadipocyte 3T3-L1 cells were measured by Oil Red-O staining assay. Treatment with extracts of resveratrol-amplified grape skin decreased lipid accumulation and glycerol-3-phosphate dehydrogenase activity without affecting 3T3-L1 cell viability. Grape skin extract treatment resulted in significantly attenuated expression of key adipogenic transcription factors, including peroxisome proliferator-activated receptor, CCAAT/enhancer-binding proteins, and their target genes (FAS, aP2, SCD-1, and LPL). These results indicate that resveratrol-amplified grape skin extracts may be useful for preventing obesity by regulating lipid metabolism.

• Preventive Nutrition and Food Science
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• 제20권4호
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• pp.253-259
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• 2015

Chronic low-grade inflammation is associated with obesity. This study investigated effect of high hydrostatic pressure extract of red ginseng (HRG) on inflammation in rats with high-fat (HF) diet induced obesity. Male, Sprague-Dawley rats (80~110 g) were randomly divided into two groups, and fed a 45% HF diet (HF) and a 45% HF diet containing 1.5% HRG (HF+HRG) for 14 weeks. At the end of the experiment, the serum leptin level was reduced by the HRG supplementation. The mRNA expression of genes related to adipogenesis including peroxisome proliferator-activated receptor-gamma and adipocyte protein 2 was down-regulated in the white adipose tissue (WAT). The mRNA levels of major inflammatory cytokines such as tumor necrosis factor-${\alpha}$, monocyte chemoattractant protein 1, and interleukin-6 were remarkably down-regulated by the HRG in WAT. These results suggest that HRG might be beneficial in ameliorating the inflammation-associated health complications by suppressing adipogenic and pro-inflammatory gene expression.

• Ocean and Polar Research
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• 제37권4호
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• pp.279-285
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• 2015

In this study, the potential capacity of the crude extract and its solvent fractions from S. siliquanstrum against adipocyte differentiation were evaluated in 3T3-L1 adipocytes. The anti-adipogenic effect of S. siliquanstrum was evidenced by the fact that its crude extract decreases the lipid accumulation of differentiating cells and the expression levels of crucial adipogenesis markers, peroxisome proliferator-activated receptor $(PPAR){\gamma}$ and CCAAT/enhancer-binding protein $(C/EBP){\alpha}$. All solvent fractions except the water fraction showed an observable decrease in lipid accumulation and $PPAR{\gamma}$ and $C/EBP{\alpha}$ expressions. In conclusion, these results suggest that S. siliquanstrum possesses obesity inhibiting components, which may possibly be used as a valuable anti-obesity agent for reducing the risk of obesity.