• Title/Summary/Keyword: PPAR${\alpha}$

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The Regulation of Chemerin and CMKLR1 Genes Expression by TNF-α, Adiponectin, and Chemerin Analog in Bovine Differentiated Adipocytes

  • Suzuki, Y.;Hong, Y.H.;Song, S.H.;Ardiyanti, A.;Kato, D.;So, K.H.;Katoh, K.;Roh, Sang-Gun
    • Asian-Australasian Journal of Animal Sciences
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    • v.25 no.9
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    • pp.1316-1321
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    • 2012
  • Adipokines, adipocyte-derived protein, have important roles in various kinds of physiology including energy homeostasis. Chemerin, one of adipocyte-derived adipokines, is highly expressed in differentiated adipocytes and is known to induce macrophage chemotaxis and glucose intolerance. The objective of the present study was to investigate the changes of chemerin and the chemokine-like-receptor 1 (CMKLR1) gene expression levels during differentiation of the bovine adipocyte and in differentiated adipocytes treated with tumor necrosis factor-${\alpha}$ (TNF-${\alpha}$), adiponectin, leptin, and chemerin (peptide analog). The expression levels of the chemerin gene increased at d 6 and 12 of the differentiation period accompanied by increased cytoplasm lipid droplets. From d 6 onward, peroxisome proliferator-activated receptor-${\gamma}2$ (PPAR-${\gamma}2$) gene expression levels were significantly higher than that of d 0 and 3. In contrast, CMKLR1 expression levels decreased at the end of the differentiation period. In fully differentiated adipocytes (i.e. at d 12), the treatment of TNF-${\alpha}$ and adiponectin upregulated both chemerin and CMKLR1 gene expression levels, although leptin did not show such effects. Moreover, chemerin analog treatment was shown to upregulate chemerin gene expression levels regardless of doses. These results suggest that the expression of chemerin in bovine adipocyte might be regulated by chemerin itself and other adipokines, which indicates its possible role in modulating the adipokine secretions in adipose tissues.

Effects of Carthamus Tinctorius Extract on Adipogenic Differentiation of Mouse Bone Marrow-Derived Mesenchymal Stromal Stem Cells (홍화 추출물이 생쥐 골수 유래 중간엽 줄기세포의 지방분화에 미치는 영향)

  • Yu, Sung-ryul;Shin, Seon-mi
    • The Journal of Internal Korean Medicine
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    • v.38 no.1
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    • pp.1-9
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    • 2017
  • Objective: This study investigated the effect of purified Carthamus tinctorius (C. tinctorius) extracted with a hot water and ethanol method on adipogenic differentiation of mouse bone marrow-derived mesenchymal stromal stem cells (mBMSCs). Methods: The C. tinctorius was extracted using hot water and ethanol. The samples were concentrated by a rotary evaporator and were then dried using a freeze-dryer. The mBMSCs were cultured and maintained in a minimum essential medium eagle alpha (${\alpha}-MEM$) supplemented with 10% FBS and 1% antibiotic antimycotic solution. To induce adipogenic differentiation, the cells were treated with Dulbecco's modified eagle's medium-low glucose (DMEM-LG) containing 1 mg/mL insulin, 1 mM dexamethasone, and 0.5 mM 3-isobutyl-1-methylxanthine. To evaluate the adipogenic differentiation ability, oil-red O staining was performed after adipogenic differentiation for 21 days. The mRNA expression and protein level of adipogenic-related genes were quantified by quantitative real-time PCR and western blotting, respectively. Results: In the results of the MTT assay, no concentrations of C. tinctorius extracts showed toxicity on mBMSCs, so we fixed the treatment concentration of the extract at 100 ng/mL. In oil-red O staining, the water-C. tinctorius extract treatment significantly decreased adipogenic differentiation compared with the control and ethanol extract groups. The water-C. tinctorius extract group in particular showed reduced mRNA and protein expression of Peroxisome proliferator-activated receptor gamma ($Ppar{\gamma}$) and CCAAT/enhancer-binding protein alpha ($C/ebp{\alpha}$), which are adipogenic-related transcription factors. Conclusion: These data suggest that extract of C. tinctorius decreased the adipogenic differentiation of mBMSCs, while only water-C. tinctorius extract had an effect on different adipogenesis in mBMSCs. The C. tinctorius will be a useful therapeutic reagent for the prevention of obesity-related diseases such as diabetes, hyperlipidemia, coronary artery disease, and osteoporosis.

Retinoid X Receptor α Overexpression Alleviates Mitochondrial Dysfunction-induced Insulin Resistance through Transcriptional Regulation of Insulin Receptor Substrate 1

  • Lee, Seung Eun;Koo, Young Do;Lee, Ji Seon;Kwak, Soo Heon;Jung, Hye Seung;Cho, Young Min;Park, Young Joo;Chung, Sung Soo;Park, Kyong Soo
    • Molecules and Cells
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    • v.38 no.4
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    • pp.356-361
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    • 2015
  • Mitochondrial dysfunction is associated with insulin resistance and diabetes. We previously showed that retinoid X receptor ${\alpha}$ ($RXR{\alpha}$) played an important role in transcriptional regulation of oxidative phosphorylation (OXPHOS) genes in cells with mitochondrial dysfunction caused by mitochondrial DNA mutation. In this study, we investigated whether mitochondrial dysfunction induced by incubation with OXPHOS inhibitors affects insulin receptor substrate 1 (IRS1) mRNA and protein levels and whether $RXR{\alpha}$ activation or overexpression can restore IRS1 expression. Both IRS1 and $RXR{\alpha}$ protein levels were significantly reduced when C2C12 myotubes were treated with the OXPHOS complex inhibitors, rotenone and antimycin A. The addition of $RXR{\alpha}$ agonists, 9-cis retinoic acid (9cRA) and LG1506, increased IRS1 transcription and protein levels and restored mitochondrial function, which ultimately improved insulin signaling. $RXR{\alpha}$ overexpression also increased IRS1 transcription and mitochondrial function. Because $RXR{\alpha}$ overexpression, knock-down, or activation by LG1506 regulated IRS1 transcription mostly independently of mitochondrial function, it is likely that $RXR{\alpha}$ directly regulates IRS1 transcription. Consistent with the hypothesis, we showed that $RXR{\alpha}$ bound to the IRS1 promoter as a heterodimer with peroxisome proliferator-activated receptor ${\delta}$ ($PPAR{\delta}$). These results suggest that $RXR{\alpha}$ overexpression or activation alleviates insulin resistance by increasing IRS1 expression.

Anti-obese effects of mulberry (Morus alba L.) root bark through the inhibition of digestive enzymes and 3T3-L1 adipocyte differentiation (소화효소 저해 및 지방세포 분화 억제활성에 의한 상백피의 항비만 효능)

  • Wu, Yong-Xiang;Kim, You-Jeong;Li, Sha;Yun, Myung-Chul;Yoon, Jin-Mi;Kim, Jin-Young;Cho, Sung-Il;Son, Kun-Ho;Kim, Taewan
    • Food Science and Preservation
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    • v.22 no.1
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    • pp.27-35
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    • 2015
  • Anti-obese effects of mulberry (Morus alba L.) root bark was investigated in vitro by measuring its inhibitory effect against 3T3-L1 preadipocyte differentiation and digestive enzymes such as ${\alpha}$-amylase, ${\alpha}$-glucosidase and pancreatic lipase. Ethanol extract of mulberry root bark (MRE) showed the potent inhibitory activities on ${\alpha}$-amylase, ${\alpha}$-glucosidase and pancreatic lipase with $IC_{50}$ values of $7.86{\pm}0.36$, $0.12{\pm}0.03$ and $7.93{\pm}0.11mg/mL$, respectively. Furthermore, MRE significantly suppressed cellular lipid accumulation in 3T3-L1 cells in a dose-dependent manner. To elucidate the mechanism of MRE, we performed qRT-PCR and Western blotting for the expression of genes related with adipogenesis and lipogenesis. Treatment of MRE markedly suppressed the protein expression of $PPAR{\gamma}$, $C/EBP{\alpha}$ and SREBP-1c, as well as FAS and ACC, which are the key transcription factors and metabolic enzymes in adipogenesis and lipogenesis. In addition, qRT-PCR analysis indicated that the anti-adipogenesis effect of MRE might be due to its inhibition at transcription levels. These results demonstrate that MRE can effectively suppress adipocyte differentiation and inhibit key enzymes related to obesity. Our findings suggest that mulberry root bark may have a potential benefit in preventing obesity.

15-DEOXY-$\Delta^{12,14}$-PROSTAGLANDIN $J_2$, A LIGAND FOR EROXISOME PROLIFERATOR-ACTIVATED RECEPTOR-$\gamma$ INDUCES APOPTOSIS IN NEUROBLASTOMA CELLS

  • Kim, Eun-Joung;Jung, Kyoung-Mi;Park, Ki-Sook;Oh, Jae-Ho;Song, Chi-Won;Chung, Soo-Youn;Hong, Jin-Tae
    • Proceedings of the Korean Society of Toxicology Conference
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    • 2001.05a
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    • pp.167-167
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    • 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)

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Polycystic kidney disease and therapeutic approaches

  • Park, Eun-Young;Woo, Yu-Mi;Park, Jong-Hoon
    • BMB Reports
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    • v.44 no.6
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    • pp.359-368
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    • 2011
  • Polycystic kidney disease (PKD) is a common genetic disorder in which extensive epithelial-lined cysts develop in the kidneys. In previous studies, abnormalities of polycystin protein and its interacting proteins, as well as primary cilia, have been suggested to play critical roles in the development of renal cysts. However, although several therapeutic targets for PKD have been suggested, no early diagnosis or effective treatments are currently available. Current developments are active for treatment of PKD including inhibitors or antagonists of PPAR-${\gamma}$, TNF-${\alpha}$, CDK and VEGF. These drugs are potential therapeutic targets in PKD, and need to be determined about pathological functions in human PKD. It has recently been reported that the alteration of epigenetic regulation, as well as gene mutations, may affect the pathogenesis of PKD. In this review, we will discuss recent approaches to PKD therapy. It provides important information regarding potential targets for PKD.

Anti-Obesity Effects of Salted and Unsalted Doenjang Supplementation in C57BL/6J Mice Fed with High Fat Diet (식이유도 비만 Mice에서 된장 및 무염된장의 항비만 효과)

  • Bae, Cho-Rong;Kwon, Dae Young;Cha, Youn-Soo
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.42 no.7
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    • pp.1036-1042
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    • 2013
  • The aim of the present study is to elucidate the anti-obesity effects of Doenjang with and without salt in C57BL/6J mice. For the analysis, a total of forty mice were randomly divided into four groups: normal diet group (ND), high-fat diet group (HD), high-fat diet supplemented with 20% Doenjang group (DJ), high-fat diet supplemented with 20% unsalted Doenjang group (NS). During the study period, food intake and body weight were measured daily and weekly, respectively. The animals were sacrificed after 12 weeks. Body weight gain, epididymal fat pad weight and serum triglyceride levels of DJ group were found to be significantly lower than those of the HD and NS groups. Serum total-cholesterol levels of DJ and NS groups were significantly lower as compared to the HD group. There were significant decreases in plasma insulin and leptin levels in DJ group compared with the HD and NS groups. We did not observe any significant changes in the expression of hepatic lipogenic-related gene $PPAR{\gamma}$ among the HD, DJ and NS groups. However, ACC expression was found to be significantly decreased in DJ group. Lipolysis-related gene ($PPAR{\alpha}$ and CPT-1) expression was significantly higher in the DJ group as compared to HD and NS groups. In conclusion, the results of this study showed that Doenjang supplementation lowers body weight gain and improves obesity-related parameters.

Anti-Lipogenic Effect of Functional Cereal Samples on High Sucrose Diet-Induced Non-Alcoholic Fatty Liver Disease in Mice (고당식이로 유도된 비알코올성 지방간 마우스에서 기능성 잡곡의 지질 대사 개선 효과)

  • Lee, Ko-Eun;Song, Jia-Le;Jeong, Byung-Jin;Jeong, Jong-Sung;Huh, Tae-Gon;Park, Kun-Young
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.45 no.6
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    • pp.789-796
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    • 2016
  • The anti-lipogenic effect of cereal samples on high sucrose diet (HSD)-induced non-alcoholic fatty liver disease (NAFLD) in mice was studied. We divided C57BL/6 mice into various groups based on 8 weeks of treatment with three types of cereal samples (HSD+WR, HSD diet containing 40% white rice; HSD+MCG, HSD diet containing 40% mixed cereal grain; HSD+AO-MCG, HSD diet containing 40% mixed antiobesity-cereal grain). After the experimental period, body weight changes, liver weights, serum lipid profiles, and hepatic fatty acid metabolism-related gene expression levels were determined. We found that HSD+WR, HSD+MCG, and HSD+AO-MCG treatments reduced body weight and liver weight, especially HSD+MCG and HSD+AO-MCG effectively reduced levels of serum triglycerides, total cholesterol, and low-density lipoprotein cholesterol. However, high density lipoprotein cholesterol levels increased compared to the control group. Furthermore, expression of hepatic lipogenic genes such as sterol regulatory element-binding protein-1c, acetyl-coenzyme A carboxylase, fatty acid synthase, stearoyl-coenzyme A desaturase-1, cluster of differentiation, and $PPAR-{\gamma}$ (peroxisome proliferator activated receptor ${\gamma}$) decreased, whereas expression of ${\beta}-oxidation$ genes such as $PPAR-{\alpha}$ and carnitine palmitoyl transferase-1 increased following HSD+MCG and HSD+AO-MCG treatment compared with levels in HSD+WR and control groups. These results suggest that the functional cereal samples, especially HSD+AO-MCG treatment, improved hepatic steatosis triggered by an HSD-induced imbalance in hepatic lipid metabolism.

Exmination of Anti-Obesity Effect of Regional Special Natural Products of Anthrisci radix, Psoraleae semen, Siegesbeckiae herba and Corni fructus (지역 특산 천연산물 전호, 파고지, 희첨 및 산수유의 항비만효과 규명)

  • Shin, Jin-Hyuk;Cha, Gu-Yong;Kim, Hui-Jin;Hwang, Jae-Ho;Han, Kyeong-Ho;Seo, Hyo-Jin;Shin, Tai-Sun;Oh, Suk-Jung;Kim, Jong-Deog
    • KSBB Journal
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    • v.24 no.6
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    • pp.549-555
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    • 2009
  • 4 kinds of Regional Special Natural Products (RSNPs), such as Anthrisci radix, Psoraleae semen, Siegesbeckiae herba and Corni fructus were examined to verify for anti-obesity effect. $PPAR\gamma$ (peroxisome proliferator-activated receptor $\gamma$) from 3T3-L1 cell concerning adipocyte differentiation was suppressed by different concentraton of 4 RSNPs with western blot, when treated RSNPs' extract and MDI (IBMX, Dexamethasone, Insulin) at the same time. Also, SREBP-1 (Sterol regulatory element binding protein) controlling lipogenesis and $PPAR\gamma$ expression levels were reduced by these 4 RSNPs' extract, when these chemicals after differentiation of 3T3-L1 cell. And lipid droplets were reduced by 7.5%, 14.4%, 18.3% and 30% at different concentration of Anthrisci radix from Oil Red O staining. Also, it was reduced by 2%, 4.9%, 9.3% and 38% at different concentration of Psoraleae semen. For Siegesbeckiae herba, it was inhibited by 1.4%, 6.4%, 16.4% and 30.1%, respectively. And Corni fructus was also showed by 0.9%, 6.3%, 13.7% and 33% at same concentration of Siegesbeckiae herba. These 4 kinds of RSNPs were expected for a useful material for anti-obesity materials.