• Title/Summary/Keyword: $PPAR_{\gamma}$

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Anti-Diabetic Effect of Puerarin Isolated from Puerariae Radix (갈근(葛根)으로부터 분리된 puerarin의 항당뇨 효과)

  • Lim, Hyun-Ae;Lim, Ji-Sun;Kim, Jong-Sang
    • Current Research on Agriculture and Life Sciences
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    • v.24
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    • pp.29-35
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    • 2006
  • In this study we evaluated the anti-diabetic potential of Puerariae Radix and its isoflavone (puerarin) by investigating their inhibitory activities against digestive enzymes, ${\alpha}$-amylase, ${\alpha}$-glucosidase and lipase and effect on glucose uptake and PPAR ${\gamma}$ expression. The activities of carbohydrate digestive enzymes were not inhibited by puerarin. Glucose uptake in differentiated adipocytes was stimulated by puerarin. Furthermore, puerarin enhanced the differentiation of preadipocytes as evaluated by triacylglycerol (TG) accumulation, which is specific for differentiated adipocytes. The effect of puerarin on expression of peroxisome proliferator-activated receptor ${\gamma}$ (PPAR-${\gamma}$) gene, which is associated with obesity and dyslipidemia, was examined by both real-time PCR and reverse transcriptase PCR. The study demonstrated that puerarin increased the expression of PPAR-${\gamma}$. In conclusion, puerarin showed potential to exert anti-diabetic action by enhancing cellular glucose uptake and thereby TG accumulation in adipocyte tissue.

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Endocrine Disrupting Organotin Compounds are Potent Inducers of Imposex in Gastropods and Adipogenesis in Vertebrates

  • Iguchi, Taisen;Katsu, Yoshinao;Horiguchi, Toshihiro;Watanabe, Hajime;Blumberg, Bruce;Ohta, Yasuhiko
    • Molecular & Cellular Toxicology
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    • v.3 no.1
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    • pp.1-10
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    • 2007
  • The persistent and ubiquitous environmental contaminant, tributyltin chloride (TBT), induces not only imposex in gastropods but also the differentiation of adipocytes in vitro and increases adipose mass in vivo in vertebrates. TBT is a nanomolar affinity ligand for retinoid X receptor (RXR) in the rock shell(Thais clavigera) and for both the RXR and the peroxisome proliferator activated receptor $\gamma(PPAR\gamma)$ in the amphibian (Xenopus laevis), mouse, and human. The molecular mechanisms underlying induction of imposex by TBT have not been clarified, though several hypotheses are proposed. TBT promotes adipogenesis in the murine 3T3-L1 cell model and perturbs key regulators of adipogenesis and lipogenic pathways in vivo primarily through activation of RXR and $PPAR\gamma$. Moreover, in utero exposure to TBT leads to strikingly elevated lipid accumulation in adipose depots, liver, and testis of neonate mice and results in increased adipose mass in adults. In X. laevis, ectopic adipocytes form in and around gonadal tissues following organotin, RXR or $PPAR\gamma$ ligand exposure. TBT represents the first example of an environmental endocrine disrupter that promotes adverse effects from gastropods to mammals.

Genipin Selectively Inhibits TNF-${\alpha}$-activated VCAM-1 But Not ICAM-1 Expression by Upregulation of PPAR-${\gamma}$ in Human Endothelial Cells

  • Jung, Seok-Hwa;Mun, Lidiya;Kim, Hye-Jung;Seo, Han-Geuk;Lee, Jae-Heun;Kwak, Jong-Hwan;Lee, Dong-Ung;Chang, Ki-Churl
    • The Korean Journal of Physiology and Pharmacology
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    • v.15 no.3
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    • pp.157-162
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    • 2011
  • Vascular inflammation process has been suggested to be an important risk factor in the development of atherosclerosis. Recently we reported that induction of peroxisome proliferator-activated receptor-${\gamma}$ (PPAR-${\gamma}$) selectively inhibits vascular cell adhesion molecule-1 (VCAM-1) but not intercellular cell adhesion molecule-1 (ICAM-1) in tumor necrosis factor (TNF)-${\alpha}$-activated human umbilical vein endothelial cells (HUVEC). In this study, we investigated whether genipin inhibits expression of cellular adhesion molecules, which is relevant to inflammation. Pretreatment with genipin reduced reactive oxygen species (ROS) production and expression of VCAM-1, but not ICAM-1 in TNF-${\alpha}$-activated HUVEC. Genipin dose- and time-dependently increased PPAR-${\gamma}$ expression and inhibited TNF-${\alpha}$-induced phosphorylation of Akt and PKC with different degrees. Finally, genipin prevented TNF-${\alpha}$-induced adhesion of U937 monocytic cells to HUVEC. Taken together, these results indicate that upregualtion of PPAR-${\gamma}$ by genipin selectively inhibits TNF-${\alpha}$-induced expression of VCAM-1, in which regulation of Akt and/or PKC play a key role. We concluded that genipin can be used for the treatment of cardiovascular disorders such as atherosclerosis.

Expression of the genes for peroxisome proliferator-activated receptor-γ, cyclooxygenase-2, and proinflammatory cytokines in granulosa cells from women with polycystic ovary syndrome

  • Lee, Joong Yeup;Tae, Jin Cheol;Kim, Chung Hyon;Hwang, Doyeong;Kim, Ki Chul;Suh, Chang Suk;Kim, Seok Hyun
    • Clinical and Experimental Reproductive Medicine
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    • v.44 no.3
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    • pp.146-151
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    • 2017
  • Objective: To identify differences in the expression of the genes for peroxisome proliferator-activated receptor $(PPAR)-{\gamma}$, cyclooxygenase (COX)-2, and the proinflammatory cytokines interleukin (IL)-6 and tumor necrosis factor $(TNF)-{\alpha}$ in granulosa cells (GCs) from polycystic ovary syndrome (PCOS) patients and controls undergoing controlled ovarian stimulation. Methods: Nine patients with PCOS and six controls were enrolled in this study. On the day of oocyte retrieval, GCs were collected from pooled follicular fluid. Total mRNA was extracted from GCs. Reverse transcription was performed and gene expression levels were quantified by realtime quantitative polymerase chain reaction. Results: There were no significant differences in age, body mass index, and total gonadotropin dose, except for the ratio of luteinizing hormone to follicle-stimulating hormone between the PCOS and control groups. $PPAR-{\gamma}$ and COX-2 mRNA was significantly downregulated in the GCs of PCOS women compared with controls (p= 0.034 and p= 0.018, respectively), but the expression of IL-6 and $TNF-{\alpha}$ mRNA did not show significant differences. No significant correlation was detected between the expression of these mRNA sequences and clinical characteristics, including the number of retrieved oocytes, oocyte maturity, cleavage, or the good embryo rate. Positive correlations were found among the $PPAR-{\gamma}$, COX-2, IL-6, and $TNF-{\alpha}$ mRNA levels. Conclusion: Our data may provide novel clues regarding ovarian GC dysfunction in PCOS, and indirectly provide evidence that the effect of $PPAR-{\gamma}$ agonists in PCOS might result from alterations in the ovarian follicular environment. Further studies with a larger sample size are required to confirm these proposals.

Mannosylerythritol lipids ameliorate ultraviolet A-induced aquaporin-3 downregulation by suppressing c-Jun N-terminal kinase phosphorylation in cultured human keratinocytes

  • Bae, Il-Hong;Lee, Sung Hoon;Oh, Soojung;Choi, Hyeongwon;Marinho, Paulo A.;Yoo, Jae Won;Ko, Jae Young;Lee, Eun-Soo;Lee, Tae Ryong;Lee, Chang Seok;Kim, Dae-Yong
    • The Korean Journal of Physiology and Pharmacology
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    • v.23 no.2
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    • pp.113-120
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    • 2019
  • Mannosylerythritol lipids (MELs) are glycolipids and have several pharmacological efficacies. MELs also show skin-moisturizing efficacy through a yet-unknown underlying mechanism. Aquaporin-3 (AQP3) is a membrane protein that contributes to the water homeostasis of the epidermis, and decreased AQP3 expression following ultraviolet (UV)-irradiation of the skin is associated with reduced skin moisture. No previous study has examined whether the skin-moisturizing effect of MELs might act through the modulation of AQP3 expression. Here, we report for the first time that MELs ameliorate the UVA-induced downregulation of AQP3 in cultured human epidermal keratinocytes (HaCaT keratinocytes). Our results revealed that UVA irradiation decreases AQP3 expression at the protein and messenger RNA (mRNA) levels, but that MEL treatment significantly ameliorated these effects. Our mitogen-activated protein kinase inhibitor analysis revealed that phosphorylation of c-Jun N-terminal kinase (JNK), but not extracellular signal-regulated kinase or p38, mediates UVA-induced AQP3 downregulation, and that MEL treatment significantly suppressed the UVA-induced phosphorylation of JNK. To explore a possible mechanism, we tested whether MELs could regulate the expression of peroxidase proliferator-activated receptor gamma ($PPAR-{\gamma}$), which acts as a potent transcription factor for AQP3 expression. Interestingly, UVA irradiation significantly inhibited the mRNA expression of $PPAR-{\gamma}$ in HaCaT keratinocytes, whereas a JNK inhibitor and MELs significantly rescued this effect. Taken together, these findings suggest that MELs ameliorate UVA-induced AQP3 downregulation in HaCaT keratinocytes by suppressing JNK activation to block the decrease of $PPAR-{\gamma}$. Collectively, our findings suggest that MELs can be used as a potential ingredient that modulates AQP3 expression to improve skin moisturization following UVA irradiation-induced damage.

Ponciri Fructus Extract Induces Lipogenesis through Transcription Factor SREBP-1 Activation (지실 추출물의 전사인자 SREBP-1 활성에 의한 지질 생성 촉진)

  • Kim, Dae-Sung;Jeon, Byoung-Kook;Mun, Yeun-Ja;Lee, Ghang-Tai;Lee, Kun-Kuk;Woo, Won-Hong
    • YAKHAK HOEJI
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    • v.56 no.4
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    • pp.268-273
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    • 2012
  • This study was to explore the lipogenic effect by ethanol extract of ponciri fructus (EPF) and possible molecular mechanisms in sebocyte. When SZ95 sebocyte cell line were treated with the EPF, lipid droplets were accumulated in the majority of cells. EPF increased expression of sterol regulatory element-binding protein-1 (SREBP-1) and fatty acid synthase (FAS) in the SZ95 cells. EPF augmented expression of PPAR-${\beta}$ and PPAR-${\gamma}$ but not that of PPAR-${\alpha}$. These results suggest that EPF induces lipogenesis in SZ95 cells through SREBP-1, PPAR-${\beta}$ and PPAR-${\gamma}$ activations.

Anti-adipogenic Effects of Dongchimi Nano Juice in Mouse 3T3-L1 Adipocytes

  • Kong, Chang-Suk;Lee, Sun-Hyun;Seo, Jung-Ok;Park, Kun-Young;Rhee, Sook-Hee
    • Preventive Nutrition and Food Science
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    • v.11 no.4
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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.

Activation of $PPAR{\alpha}$ Attenuates $IFNP{\gamma}$ and IL-$1{\beta}$-induced Cell Proliferation in Astrocytes: Involvement of IL-6 Independent Pathway

  • Lee, Jin-Koo;Seo, Eun-Min;Lee, Sang-Soo;Park, Soo-Hyun;Sim, Yun-Beom;Jung, Jun-Suh;Kim, Seon-Mi;Suh, Hong-Won
    • The Korean Journal of Physiology and Pharmacology
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    • v.14 no.3
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    • pp.185-189
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    • 2010
  • The present study demonstrates the effect of fibrates, agonists of $PPAR{\alpha}$ on cytokines-induced proliferation in primary cultured astrocytes. Alone or combination treatment with cytokines, such as IL-$1{\beta}$ (10 ng/ml), $IFNP{\gamma}$ (10 ng/ml), and TNF-$\alpha$ (10 ng/ml) cause a significant increase of cell proliferation in a time-dependent manner. Treatment of astrocytes with bezafibrate and fenofibrate (0, 5, and $10\;{\mu}M$) reduced the $IFNP{\gamma}$ and IL-$1{\beta}$-induced cell proliferation in a dose-dependent manner. To address the involvement of IL-6 on the $IFNP{\gamma}$ and IL-$1{\beta}$-induced cell proliferation, released IL-6 level was measured. $IFNP{\gamma}$ and IL-$1{\beta}$ cause an increase of released IL-6 protein level in a time-dependent manner. Furthermore, pretreatment with IL-6 antibody (0, 0.1, 1, 2.5, and 5 ng/ml) dose-dependently inhibited the $IFNP{\gamma}$ and IL-$1{\beta}$-induced cell proliferation. However, bezafibrate and fenofibrate did not affect increased mRNA and protein levels of IL-6 in $IFNP{\gamma}$ and IL-$1{\beta}$-stimulated astrocytes. Taken together, these results clearly suggest that activation of $PPAR{\alpha}$ attenuates the $IFNP{\gamma}$ and IL-$1{\beta}$-induced cell proliferation through IL-6 independent pathway.

Inhibitory Effect of the Ethanol Extract of Torilis Japonica Decandolle on Adipocyte Differentiation in 3T3-L1 Cells (사상자 에탄올 추출물의 지방세포 분화 억제 효과)

  • Nam, Gun He;Wee, Ji-Hyang;Kim, Sang Yung;Baek, Ji-Young;Kim, Young Min
    • Journal of Life Science
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    • v.29 no.9
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    • pp.1016-1022
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    • 2019
  • Owing to increased interest in preventing obesity in an aging society, both men and women spend considerable amount of cost on obesity managements. In this study, we investigated the natural substances on anti-obesity activities in 3T3-L1 pre-adipocytes. Also, to improve anti-obesityeffects, research using 3T3-L1 pre-adipocytes cells is crucial. The anti-obesity effect of 70% ethanol extract from Torilis Japonica Decandolle on the differentiation of 3T3-L1 pre-adipocytes to adipocytes was investigated by suppressing adipocyte differentiation and lipid accumulation with Oil Red O assay, and western blot analysis. Compared to the control, 70% ethanol extract of Torilis Japonica Decandolle was significantly inhibited adipocyte differentiation and intracellular triglyceride (TG) level at a concentration of $100{\mu}g/ml$. To determine the mechanism of reduction in TG content, we determined the level of protein expression of obesity-related proteins, such as peroxisome-proliferatorsactivated-receptor-${\gamma}$ ($PPAR{\gamma}$) and CCAAT enhancer-binding-proteins-${\alpha}$ ($C/EBP{\alpha}$), and Acetyl-CoA carboxylase (ACC) phosphorylation. As a results, 70% ethanol extract of Torilis Japonica Decandolle significantly decreased protein expression of $PPAR{\gamma}$, $C/EBP{\alpha}$ and ACC phosphorylation. These results indicate that 70% ethanol extract of Torilis Japonica Decandolle is the most effective candidate for preventing obesity. However further studies will be needed to identify the active compounds that confer the anti-obesity activity of Torilis Japonica Decandolle.