• Biomolecules & Therapeutics
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• v.31 no.3
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• pp.312-318
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• 2023

The natural flavonoid macakurzin C (1) exhibited adiponectin biosynthesis-inducing activity during adipogenesis in human bone marrow mesenchymal stem cells and its molecular mechanism was directly associated with a pan-peroxisome proliferator-activated receptor (PPAR) modulator affecting all three PPAR subtypes α, γ, and δ. In this study, increases in adiponectin biosynthesis-inducing activity by macakurzin C derivatives (2-7) were studied. The most potent adiponectin biosynthesis-inducing compound 6, macakurzin C 3,5-dimethylether, was elucidated as a dual PPARα/γ modulator. Compound 6 may exhibit the most potent activity because of the antagonistic relationship between PPARδ and PPARγ. Docking studies revealed that the O-methylation of macakurzin C to generate compound 6 significantly disrupted PPARδ binding. Compound 6 has therapeutic potential in hypoadiponectinemia-related metabolic diseases.

• BMB Reports
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• v.42 no.2
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• pp.91-95
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• 2009

Peroxisome proliferator-activated receptor $\alpha$ and estrogen are believed to be involved in metabolic changes leading to obesity. To test this relationship, we divided female wildtype and PPAR$\alpha$-deficient mice fed on a high fat diet into the following groups: mock-operated, ovariectomized (OVX), and $E_2$-treated. The visceral white adipose tissue and plasma cholesterol levels were increased significantly in wild type OVX and decreased in the $E_2$-treated group, but interestingly not in PPAR$\alpha$-deficient mice. The mRNA levels of lipoprotein lipase in adipose tissue were also increased in only wild type OVX and decreased significantly in $E_2$-treated mice. These novel results suggest the possibility of signaling crosstalk between PPAR$\alpha$ and $E_2$, causing obesity in vivo.

• Molecules and Cells
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• v.24 no.3
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• pp.388-393
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• 2007

Osteonecrosis of the femoral head (ONFH) is a multifactorial disease to which certain individuals are more at risk. Altered lipid metabolism is one of the major risk factors for osteonecrosis, especially corticosteroid therapy and alcoholism. Peroxisome Proliferator-Activated Receptor-${\gamma}$ ($PPAR{\gamma}$) plays a crucial role in differentiation of mesenchymal cells to adipocytes, lipid homeostasis, and bone metabolism. To investigate the possible association between $PPAR{\gamma}$ gene variants and susceptibility to ONFH, we genotyped three common polymorphisms (-796A > G, +34C > G[Pro12Ala], and +82466C > T[His477His]) in 448 ONFH patients and 336 control subjects. Genotypes, allele frequencies, and haplotypes of the polymorphisms in the complete set of patients as well as in subgroups by sex or etiology were not significantly different from those in the control group. This suggests that the examined polymorphisms and haplotypes of the $PPAR{\gamma}$ gene are unlikely to be associated with susceptibility to ONFH.

• Clinical and Experimental Pediatrics
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• v.56 no.4
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• pp.151-158
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• 2013

Purpose: We investigated the mRNA levels of peroxisome proliferator-activated receptor (PPAR)-${\alpha}$, PPAR-${\gamma}$, adipokines, and cytokines in the lung tissue of lean and obese mice with and without ovalbumin (OVA) challenge, and the effect of rosiglitazone, a PPAR-${\gamma}$ agonist. Methods: We developed 6 mice models: OVA-challenged lean mice with and without rosiglitazone; obese mice with and without rosiglitazone; and OVA-challenged obese mice with and without rosiglitazone. We performed real-time polymerase chain reaction for leptin, leptin receptor, adiponectin, vascular endothelial growth factor (VEGF), tumor necrosis factor (TNF)-${\alpha}$, transforming growth factor (TGF)-${\beta}$, PPAR-${\alpha}$ and PPAR-${\gamma}$ from the lung tissue and determined the cell counts and cytokine levels in the bronchoalveolar lavage fluid. Results: Mice with OVA challenge showed airway hyperresponsiveness. The lung mRNA levels of PPAR${\alpha}$ and PPAR-${\gamma}$ increased significantly in obese mice with OVA challenge compared to that in other types of mice and decreased after rosiglitazone administeration. Leptin and leptin receptor expression increased in obese mice with and without OVA challenge and decreased following rosiglitazone treatment. Adiponectin mRNA level increased in lean mice with OVA challenge. Lung VEGF, TNF-${\alpha}$, and TGF-${\beta}$ mRNA levels increased in obese mice with and without OVA challenge compared to that in the control mice. However, rosiglitazone reduced only TGF-${\beta}$ expression in obese mice, and even augmented VEGF expression in all types of mice. Rosiglitazone treatment did not reduce airway responsiveness, but increased neutrophils and macrophages in the bronchoalveolar lavage fluid. Conclusion: PPAR-${\alpha}$ and PPAR-${\gamma}$ expressions were upregulated in the lung tissue of OVA-challenged obese mice however, rosiglitazone treatment did not downregulate airway inflammation in these mice.

• Proceedings of the PSK Conference
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• 2003.10b
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• pp.177.2-177.2
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• 2003

Thiazolidinediones (TZDs) are a new class of compound that increase insulin sensitivity in type 2 diabetic patients. Thiazolidinediones (TZDs) act as ligands for a member of the nuclear hormone receptor superfamily, peroxisome proliferator-activated receptor-$\gamma$ (PPAR-$\gamma$), which is highly expressed in fatty tissue and, moreover, has been shown to play an important role in fat cell differentiation. The strong interaction between the antidiabetic activity ofTZDs and their ability to activate PPAR-$\gamma$ suggests that PPAR-$\gamma$, through downstream-regulated genes, mediates the effects of TZDs. (omitted)

• Journal of Life Science
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• v.24 no.1
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• pp.67-73
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• 2014

This study was conducted to investigate the effects of supplementation with Opuntia humifusa on the expression of peroxisome proliferator-activated receptor-delta (PPAR-${\delta}$), peroxisome proliferator-activated receptor-gamma (PPAR-${\gamma}$) and peroxisome proliferator-activated receptor gamma coactivator-1alpha (PGC-$1{\alpha}$) in the skeletal muscle of rats fed a high-fat diet. Sixteen Sprague-Dawley male rats at 6 weeks of age were randomly divided into 2 groups: a control diet group (CG, n=8) and an experimental diet group (EG, n=8). The rats were fed a high-fat diet (CG) or a high-fat diet supplemented with 5% O. humifusa (EG) for 8 weeks. The results showed that the abdominal fat pad and epididymal fat pad weights were significantly lower in the EG than in the CG (p<0.01). In the blood, serum glucose, triglycerides, and total cholesterol in the EG group were lower than in the CG (p<0.01). The expression of PPAR-${\gamma}$ and PGC-$1{\alpha}$ protein in the skeletal muscle of the EG was increased compared with that of the CG (p<0.05). These results indicate that 8 weeks of O. humifusa supplementation lowers serum glucose and triglyceride levels and suppresses weight gain by reducing fat weight through an increase in the expression of PPAR-${\gamma}$ and PGC-$1{\alpha}$ in the muscle tissue of rats.

• Proceedings of the PSK Conference
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• 2003.04a
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• pp.247.1-247.1
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• 2003

PPAR-$\gamma$(Peroxisome Proliferator-Activated Receptor $\gamma$) 리간드들은 논문 조사를 통해 이루어졌다. PPAR-$\gamma$의 45개 알려진 화합물들을 찾았고, 12 생물활성 화합물을 선택했다. 리간드(rosiglitazone)과 단백질의 결합된 구조는 (1fm6)는 PDB로부터 획득했고, 단백질 coordinate를 가져와 PPAR의 활성 영역 잔기들은 확인했다. (2TYR, 1SER, 1HIS). CoMFA와 Flexi Dock을 통해 단백질과 리간드 사이의 상호작용과 결합에너지에 대한 상호 관계를 밝혔다.

• Radiation Oncology Journal
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• v.30 no.2
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• pp.88-95
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• 2012

Purpose: The fibrates are ligands for peroxisome proliferator-activated receptor (PPAR) ${\alpha}$ and used clinically as hypolipidemic drugs. The fibrates are known to cause peroxisome proliferation, enhance superoxide dismutase (SOD) expression and catalase activity. The antioxidant actions of the fibrates may modify radiation sensitivity. Here, we investigated the change of the radiation sensitivity in two cervix cancer cell lines in combination with fenofibrate (FF). Materials and Methods: Activity and protein expression of SOD were measured according to the concentration of FF. The mRNA expressions were measured by using real time reverse-transcription polymerase chain reaction. Combined cytotoxic effect of FF and radiation was measured by using clonogenic assay. Results: In HeLa cells total SOD activity was increased with increasing FF doses up to 30 ${\mu}M$. In the other hand, the catalase activity was increased a little. As with activity the protein expression of SOD1 and SOD2 was increased with increasing doses of FF. The mRNAs of SOD1, SOD2, $PPAR{\alpha}$ and $PPAR{\gamma}$ were increased with increasing doses of FF. The reactive oxygen species (ROS) produced by radiation was decreased by preincubation with FF. The surviving fractions (SF) by combining FF and radiation was higher than those of radiation alone. In Me180 cells SOD and catalase activity were not increased with FF. Also, the mRNAs of SOD1, SOD2, and $PPAR{\alpha}$ were not increased with FF. However, the mRNA of $PPAR{\gamma}$ was increased with FF. Conclusion: FF can reduce radiation sensitivity by ROS scavenging via SOD induction in HeLa. SOD induction by FF is related with $PPAR{\alpha}$.

• Journal of Korean Medicine for Obesity Research
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• v.15 no.2
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• pp.104-110
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• 2015

Objectives: The herb of Agastache rugosa (AR) is a traditional herbal medicine used for colds, vomiting and furuncles. However, there are few reports to investigate the inhibitory effects of AR on obesity. In this study, the effects of AR on high fat diet (HFD)-induced obesity and its mechanism of actions were investigated in experimental animals. Methods: The mice were fed HFD for 4 weeks to induce obesity. After randomly divided into normal fat diet, HFD and AR groups, 200 mg/kg of AR was administrated for 4 weeks with continuous HFD feeding while vehicle was orally treated to HFD group. Food intake and body weight were recorded weekly. Results: Increased body weight by HFD was improved by AR treatment. AR administration inhibited an increase of visceral fat weight as well as adipocyte hypertrophy. Hepatic steatosis was ameliorated in AR-treated mice. In addition, treatment of AR attenuated the expression of adipogenic transcription factor, peroxisome proliferator-activated receptor (PPAR)-gamma in the epididymal adipose tissue. Also the increased serum leptin level by HFD was maintained in AR group, leading to inhibition of food intake. Conclusions: AR treatment showed inhibitory effects on HFD-induced obesity by inhibition of PPAR-gamma and reduction of food intake. AR could be an alternative treatment for obesity.

• Journal of the Society of Cosmetic Scientists of Korea
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• v.35 no.2
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• pp.117-123
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• 2009

Magnolia extract, prepared from the Chinese herb Magnolia officinalis, is known for its potent anti-oxidative and anti-inflammatory effects. In this report, we showed that Magnolia extract inhibits adipocyte differentiation, as evidenced by reduced triglyceride (TG) accumulation. Also, Magnolia extract increased hormone sensitive lipase (HSL) protein level, and decreased the adipogenic transcription factor peroxisome proliferator activated receptor (PPAR)-${\gamma}$ protein and their corresponding mRNA. Our results suggest a potential apllication of Magnolia extract as anti-obesity agents inhibits adipocyte differentiation through the down-regulation of adipogenic transcription factors and other adipocyte-specific genes.