• Biomolecules & Therapeutics
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• v.25 no.5
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• pp.504-510
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• 2017

Inhibitor of nuclear factor kappa-B kinase beta ($IKK{\beta}$) plays a critical role in cell proliferation and inflammation in various cells by activating $NF-{\kappa}B$ signaling. However, the interrelationship between peroxisome proliferator-activated receptor ${\alpha}$ ($PPAR{\alpha}$) and $IKK{\beta}$ in cell proliferation is not clear. In this study, we investigated the possible role of $PPAR{\alpha}$ in the hepatic cell death in the absence of $IKK{\beta}$ gene using liver-specific Ikkb-null ($Ikkb^{F/F-AlbCre}$) mice. To examine the function of $PPAR{\alpha}$ activation in hepatic cell death, wild-type ($Ikkb^{F/F}$) and $Ikkb^{F/F-AlbCre}$ mice were treated with $PPAR{\alpha}$ agonist Wy-14,643 (0.1% w/w chow diet) for two weeks. As a result of Wy-14,643 treatment, apoptotic markers including caspase-3 cleavage, poly (ADP-ribose) polymerase (PARP) cleavage and TUNEL-positive staining were significantly decreased in the $Ikkb^{F/F-AlbCre}$ mice. Surprisingly, Wy-14,643 increased the phosphorylation of p65 and STAT3 in both Ikkb and $Ikkb^{F/F-AlbCre}$ mice. Furthermore, BrdU-positive cells were significantly increased in both groups after treatment with Wy-14,643. Our results suggested that $IKK{\beta}-derived$ hepatic apoptosis could be altered by $PPAR{\alpha}$ activation in conjunction with activation of $NF-{\kappa}B$ and STAT3 signaling.

• Journal of Life Science
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• v.21 no.7
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• pp.997-1003
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• 2011

Menopause and obesity are associated with metabolism. The purpose of this study was to examine the changes of PPAR${\gamma}$, PGC-1(${\alpha},\;{\beta}$), NRf-1 and TFAM mRNA and mitochondria biogenesis in adipocytes and investigate the effect of swimming exercise for 6weeks on ovariectomized rats. Rats were randomly assigned to 3 groups: (1) ovariectomized rats fed with a control diet (C, n=4), (2) ovariectomized rats fed with high fat diet (H, n=4), and (3) ovariectomized rats trained to exercise and fed with high fat diet (H+EX, n=4). Exercise was performed by swimming for 5 days/wk, with a progressive increase in exercise over the course of 6 weeks. Results showed that the fat tissue weight in the H group was markedly increased (p<0.01) compared to other groups, however, regular exercise significantly decreased fat weight. The PPAR-${\gamma}$ (p<0.05), PGC-$1{\alpha}$ (p<0.01), -$1{\beta}$ (p<0.05), NRf-1 (p<0.01) and TFAM (p<0.05) mRNA expression in the adipocytes of H+EX were higher than in the H group. These results suggest that regular exercise for 6 weeks might exert positive effects by increasing PPAR-${\gamma}$, PGC-1 (${\alpha},\;{\beta}$), NRf-1 and TFAM mRNA expression and mitochondria in adipocytes. Thus, regular exercise may be helpful in the improvement of mitochondria biogenesis function in obese, ovariectomized rats.

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

• 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.

• Journal of Life Science
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• v.19 no.11
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• pp.1637-1643
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• 2009

Shikonin, a component of Lithospermum erythrorhizon Sieb. et Zucc, exerts various characteristics such as anti-inflammatory, anti-cancer and anti-obesity functions. To elucidate the molecular mechanism of shikonin-induced inhibition of adipogenesis, we analyzed the mRNA expression level of various adipogenesis-related factors including C/EBPs (CCAAT/enhancerbinding proteins) and $PPAR{\gamma}$ (peroxisome proliferator-activated receptor $\gamma$). The data showed that mRNA expressions of C/$EBP{\beta}$ and C/$EPB{\delta}$ were only slightly changed by shikonin treatment, but mRNA expressions of $PPAR{\gamma}$ and C/$EPB{\alpha}$ were significantly down-regulated. Then, we tested whether upstream regulators of C/$EBP{\beta}$ and $PPAR{\gamma}$ were involved in anti-adipogenesis of shikonin. C/$EBP{\gamma}$ and CHOP (C/EBP homologous protein), which are upstream regulators of C/$EBP{\beta}$, were not affected by shikonin treatment. On the contrary, the mRNA level of KROX20 was markedly down-regulated by shikonin treatment. These results suggest that KROX20 might regulate downstream factors of adipogenesis through C/$EBP{\beta}$-independent pathway. The expression of KLF15 (Kruppel-like factor15), which is a member of KLF family and is a upstream regulator of $PPAR{\gamma}$, was dramatically decreased by shikonin treatment, but KLF2 was not changed. Shikonin had no impact on the expression of KLF5 in the early stage of adipogenesis, but shikonin increased expression of KLF5 in the late stage of adipogenesis. Even though mRNA expression of KLF5 was moderately changed by shikonin treatment, its effect may be small compared with the effect of KLF15, which was markedly inhibited. Taken together, these results suggest that shikonin inhibits adipogenesis through the down-regulation of $PPAR{\gamma}$ and C/$EPB{\alpha}$, which is mediated by the down-regulation of two pro-adipogenic factors, KROX20 and KLF15.

• Proceedings of the Korean Society of Toxicology Conference
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• 2005.05a
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• pp.151-151
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• 2005

• Biomedical Science Letters
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• v.16 no.3
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• pp.151-159
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• 2010

The peroxisome proliferator-activated receptor $\alpha$ (PPAR$\alpha$) is a nuclear transcription factor that plays a central role in lipid metabolism and obesity. Exercise also is a powerful modifier of the manifestations of the lipid metabolism and obesity in animal models and humans with obesity and metabolic syndrome. However, effects of exercise on lipid metabolism and obesity in normal-weight younger female subjects, having functional ovaries and not metabolic disease, remain unexplained. To explore the effects of exercise on the development of obesity and its molecular mechanism in high fat diet-fed female C57BL/6J mice, we experimented the effects of swim training on body weight, adipose tissue mass, serum lipid levels, morphological changes of adipocytes and the expression of PPAR$\alpha$ target genes involved in fat oxidation in skeletal muscle tissue of female C57BL/6J mice. Swim-trained mice had significantly decreased body weight, adipose tissue mass, serum triglycerides compared with female control mice. Histological studies showed that swim training significantly decreased the average size of adipoctyes in parametrial adipose tissue. Swim training did not affect the expression of PPAR$\alpha$ mRNA in skeletal muscle. Concomitantly, swim training did not increase mRNA levels of PPAR$\alpha$ target genes responsible for fatty acid $\beta$-oxidation, such as carnitine palmitoyltransferase 1, medium chain acyl-CoA dehydrogenase, enoyl-CoA hydratase/3-hydroxyacyl-CoA dehydrogenase, and thiolase in skeletal muscle. In conclusion, these results indicate that swim training regulates lipid metabolism and obesity in high fat diet fed-female mice although swim training did not increase mRNA levels of PPAR$\alpha$ target genes involved in fatty acid $\beta$-oxidation in skeletal muscle, suggesting that swim training may prevent obesity and improve fitness through other mechanisms in female with ovaries, not through the activation of skeletal muscle PPAR$\alpha$.

• 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.

• Journal of the Korean Society of Food Science and Nutrition
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• v.45 no.5
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• pp.651-663
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• 2016

Corn silk, Job's tears, Lentinus edodes, and apple peel 70% ethanol extracts (CS, JT, LE, and AP) were studied for their antioxidant activities. CS among all extracts showed the highest antioxidant activities based on total polyphenol and flavonoid contents, 2,2-diphenyl-${\beta}$-picrylhydrazyl and 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonate) radical scavenging activity, and reducing power. Adipocyte differentiation was investigated by Oil Red O staining assay using CS, JT, LE, AP, and extract of developed bread containing corn silk, Job's tears, Lentinus edodes, and apple peel (DB) treated to 3T3-L1 adipocytes. DB1 and DB2 showed anti-adipogenic and antioxidant effects. Triglyceride (TG) accumulation in 3T3-L1 cells was measured, and among the samples tested (CS, JT, LE, and AP), CS was found to have the highest inhibitory activity against TG accumulation of differentiated 3T3-L1 adipocytes and regulated factors associated with adipogenesis. CS suppressed lipid droplet formation and adipocyte differentiation in 3T3-L1 cells in a dose-dependent manner. We examined the effects of CS on the levels of CCAAT-enhancer-binding protein ${\beta}(C/EBP{\beta})$, peroxisome proliferator activated receptor ${\gamma}(PPAR{\gamma})$, and adipocyte-specific lipid binding protein (aP2) mRNA as well as protein levels in 3T3-L1 cells treated with CS at various concentrations (0, 10, 50, and $100{\mu}g/mL$) during adipocyte differentiation and treatment with CS in 3T3-L1 adipocytes down-regulated expression of $PPAR{\gamma}$ and aP2 mRNA. CS also significantly inhibited up-regulation of $C/EBP{\beta}$, $PPAR{\gamma}$, and aP2 proteins during adipocyte differentiation. These data indicate that DBs have anti-adipogenic activity induced by CS in 3T3-L1 preadipocytes, and CS exerts anti-adipogenic activity by inhibiting expression of $C/EBP{\beta}$, $PPAR{\gamma}$, and aP2 signaling pathway in 3T3-L1 adipocytes. JT, LE, and AP had no inhibitory effects on differentiation of 3T3-L1 preadipocytes but displayed strong antioxidant effects. These results suggest that the developed bread may be a health beneficial food that can prevent or treat obesity and diseases induced by oxidative stress.

• Bulletin of the Korean Chemical Society
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• v.33 no.6
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• pp.1979-1982
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• 2012

Oxime ethers of ${\beta}$-oxo-${\gamma}$-phenylbutanoic acids were prepared to develop more effective PPAR ${\alpha}$ and ${\gamma}$ dual agonists. Among them, compound 11k exhibited potent $in$ $vitro$ activities with $EC_{50}$ of 2.5 nM and 3.3 nM in PPAR ${\alpha}$ and ${\gamma}$, respectively. It showed better glucose lowering effects than rosiglitazone 1 and improved the lipid profile like plasma triglyceride in db/db mice model.