• BMB Reports
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• v.36 no.2
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• pp.207-213
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• 2003

Peroxisome proliferator-activated receptors (PPARs) are orphan nuclear hormone receptors that are known to control the expression of genes that are involved in lipid homeostasis and energy balance. PPARs activate gene transcription in response to a variety of compounds, including hypolipidemic drugs. Most of these compounds have high affinity to the ligand-binding domain (LBD) of PPARs and cause a conformational change within PPARs. As a result, the receptor is converted to an activated mode that promotes the recruitment fo co-activators such as the steroid receptor co-activator-1 (SRC-1). Based on the activation mechanism of PPARs (the ligand binding to $PPAR{\gamma}$ induces interactions of the receptor with transcriptional co-activators), we performed Western blot and ELISA. These showed that the indomethacin, a $PPAR{\gamma}$ ligand, increased the binding between $PPAR{\gamma}$ and SRC-1 in a ligand dose-dependent manner. These results suggested that the in vitro conformational change of $PPAR{\gamma}$ by ligands was also induced, and increased the levels of the ligand-dependent interaction with SRC-1. Collectively, we developed a novel and useful ELISA system for the mass screening of $PPAR{\gamma}$ ligands. This screening system (based on the interaction between $PPAR{\gamma}$ and SRC-1) may be a promising system in the development of drugs for metabolic disorders.

• Archives of Pharmacal Research
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• v.27 no.11
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• pp.1099-1105
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• 2004

The peroxisome proliferator-activated receptors (PPARs) are a primary regulator of lipid metabolism. Potency for activation of PPAR$\gamma$, one of a subfamily of PPARs, particularly mirrors glucose lowering activity. We prepared thiazolidinediones featuring benzoxazole moiety for subtype selective PPAR$\gamma$ activators. 5-[4-[2-(Benzoxazol-2-yl-alkylamino)ethoxy]benzyl]thiazolidine-2,4-diones have been prepared by Mitsunobu reaction of benzoxazolylalkylaminoethanol 8 and hydroxybenzylthiazolidinedione 6 and their activities were evaluated. Most compounds tested were identified as potent PPAR$\gamma$ agonists.

• Proceedings of the PSK Conference
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• 2003.10b
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• pp.186.2-186.2
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• 2003

PPARs (peroxisome proliferator activated receptors) are member of nuclear hormone receptors superfamily. Activations of PPARs upon binding with ligands modulate glucose metabolite, differentiation of adipocyte, inflammation response, and so on. Thiazolidinedione analog is one of the potential antidiabetic drug that binds and activates PPAR selectively and enhances insulin sensitivity. In an effort to develop novel and effective antidiabetic thiazolidindione analogs, we have synthesized tetrahydroquinoline and para-substituted benzene-linked thiazolidinedione analogs by coupling reaction of the hydrophobic segments with hydroxybenzylthiazolidinedione.

• Proceedings of the Korean Society of Applied Pharmacology
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• 2003.11a
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• pp.117-117
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• 2003

PPARs (peroxisome proliferator activated receptors) are member of nuclear hormone receptors superfamily. Activations of PPARs upon binding with ligands modulate glucose metabolite, differentiation of adipocyte, inflammation response, and so on. Thiazolidinedione analog is one of potential antidiabetic drug that binds and activates PPARν selectively and enhances insulin sensitivity. In an effort to develop novel and effective antidiabetic thiazolidindione analogs, syntheses of benzoxazole and benzothiazole-linked thiazolidinedione analogs were performed via coupling reaction of benzoxazolylalkylaminoethanol with hydroxybenzylthiazolidinedione to develop novel and effective antidiabetic thiazolidindiones. All compounds were evaluated their biological potency by PPARν transactivation assay and revealed the similar potency with Troglitazone. However, lengthening of N-alkyl substituent did not seem to be beneficial for the activity.

• BMB Reports
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• v.40 no.4
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• pp.525-531
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• 2007

As a $\beta_2$-adrenergic agonist, clenbuterol decreases body fat, but the molecular mechanism underlying this process is unclear. In the present study, we treated 293T and L-02 cells with clenbuterol and found that clenbuterol downregulates SREBP-1c expression and upregulates CREB1 expression. Considering SREBP-1c has the function of regulating the transcription of several lipogenic enzymes, we considered that the downregulation of SREBP-1c is responsible for body fat reduction by clenbuterol. Many previous studies have found that clenbuterol markedly increases intracellular cAMP levels, therefore, we also investigated whether CREB1 is involved in this process. The data from our experiments indicate that CREB1 overexpression inhibits SREBP-1c transcription, and that this action is antagonized by CREB2, a competitive inhibitor of CREB1. Furthermore, since PPARs are able to repress SREBP-1c transcription, we investigated whether clenbuterol and CREB1 function via a pathway involving PPAR activation. However, our results showed that clenbuterol or CREB1 overexpression suppressed PPARs transcription in 293T and L-02 cells, which suggested that they impair SREBP-1c expression in other ways.

• Asian-Australasian Journal of Animal Sciences
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• v.18 no.9
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• pp.1221-1225
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• 2005

The peroxisome proliferator-activated receptors (PPARs) are members of a superfamily of nuclear hormone receptors. Lots of studies in rodents and humans have shown that PPARs were involved in lipid metabolism and adipocyte differentiation. The main objective of this work was to detect the single nucleotide polymorphisms (SNPs) in whole coding regions of peroxisome proliferator-activated receptor alpha (PPAR-$\alpha$) and gamma (PPAR-$\gamma$) genes with approach of single strand conformation polymorphism (SSCP) in the chicken population of Arber Acres broiler, Hyline layer and three Chinese native breeds (Shiqiza, Beijing You, Bai'r). Two SNPs of C1029T and C297T were found in chicken PPAR-$\alpha$ and PPAR-$\gamma$ genes respectively and each SNP found three genotypes in the experimental populations. The results showed that the distribution frequency of 3 genotypes in Arber Acres broiler, Hyline layer and Chinese native breeds had significant differences on the PPAR-$\alpha$ and PPAR-$\gamma$ gene respectively (p<0.01). Furthermore, in the PPAR-$\alpha$ gene, the results of least square estimation for genotypes and body composition traits showed the BB genotype birds had higher abdominal fat weight (AFW) and percentage of abdominal fat (AFP) than AA genotype birds (p<0.05). From these we conjecture the PPAR-$\alpha$ and PPAR-$\gamma$ genes were suffered intensive selection during the long term commercial breeding and the PPAR-$\alpha$ gene may be a major gene or linked to the major genes that impact chicken fat metabolism and the SNPs could be used in molecular assistant selection (MAS) as a genetic marker for the chicken fatness traits.

• Korean Journal of Exercise Nutrition
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• v.13 no.2
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• pp.131-140
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• 2009

The aim of this study was to investigate the expression of PPAR-α, -β/δ, -γ, PGC-1α, GLUT-4 and p-AMPK-α₂ protein in the skeletal muscle of diabetic induced-rats by endurance training combined with rosiglitazone. The expression of PPAR-α, -β/δ, -γ, PGC-1α, GLUT-4 and p-AMPK-α₂ protein in red and white gastrocnemius by western blotting. The body weight was higher in diabetic induced-rats compared to the normal rats and after the treatment of exercise combined with rosiglitazone was significantly reduced in the all group. The levels of blood glucose was higher in diabetic induced-rats compared to the normal rats and after the treatment of exercise combined with rosiglitazone was significantly reduced in the all group. The expression of PPAR-α, -γ, PGC-1α in skeletal muscle of diabetic induced-rats were increased all groups and increased significantly in the group with exercise combined with rosiglitazone. The expression of GLUT-4 and p-AMPK-α₂ protein in the skeletal muscle of diabetic induced-rats were increased all groups and increased significantly in the group with exercise combined with rosiglitazoneI. These results suggest that exercise training and rosiglitazone may act as complementary therapies for the treatment of insulin rasistance.

• BMB Reports
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• v.47 no.11
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• pp.599-608
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• 2014

As the prevalence of obesity has increased explosively over the last several decades, associated metabolic disorders, including type 2 diabetes, dyslipidemia, hypertension, and cardiovascular diseases, have been also increased. Thus, new strategies for preventing and treating them are needed. The nuclear peroxisome proliferator-activated receptors (PPARs) are involved fundamentally in regulating energy homeostasis; thus, they have been considered attractive drug targets for addressing metabolic disorders. Among the PPARs, $PPAR{\gamma}$ is a master regulator of gene expression for metabolism, inflammation, and other pathways in many cell types, especially adipocytes. It is a physiological receptor of the potent anti-diabetic drugs of the thiazolidinediones (TZDs) class, including rosiglitazone (Avandia). However, TZDs have undesirable and severe side effects, such as weight gain, fluid retention, and cardiovascular dysfunction. Recently, many reports have suggested that $PPAR{\gamma}$ could be modulated by post-translational modifications (PTMs), and modulation of PTM has been considered as novel approaches for treating metabolic disorders with fewer side effects than the TZDs. In this review, we discuss how PTM of $PPAR{\gamma}$ may be regulated and issues to be considered in making novel anti-diabetic drugs that can modulate the PTM of $PPAR{\gamma}$.

• Biomolecules & Therapeutics
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• v.22 no.4
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• pp.334-340
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• 2014

In this study, 23 oleanane-type triterpenoid saponins were isolated from a methanol extract of the roots of Pulsatilla koreana. The NF-${\kappa}B$ inhibitory activity of the isolated compounds was measured in $TNF{\alpha}$-treated HepG2 cells using a luciferase reporter system. Compounds 19-23 inhibited $TNF{\alpha}$-stimulated NF-${\kappa}B$ activation in a dose-dependent manner, with $IC_{50}$ values ranging from $0.75-8.30{\mu}M$. Compounds 19 and 20 also inhibited the $TNF{\alpha}$-induced expression of iNOS and ICAM-1 mRNA. Moreover, effect of the isolated compounds on PPARs transcriptional activity was assessed. Compounds 7-11 and 19-23 activated PPARs the transcriptional activity significantly in a dose-dependent manner, with $EC_{50}$ values ranging from $0.9-10.8{\mu}M$. These results suggest the presence of potent anti-inflammatory components in P. koreana, and will facilitate the development of novel anti-inflammatory agents.

• Proceedings of the PSK Conference
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• 2002.04a
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• pp.122.2-122.2
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• 2002