• 대한약학회:학술대회논문집
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• 대한약학회 2003년도 Proceedings of the Convention of the Pharmaceutical Society of Korea Vol.2-2
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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.

• 대한약학회:학술대회논문집
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• 대한약학회 2002년도 Proceedings of the Convention of the Pharmaceutical Society of Korea Vol.1
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• pp.150.1-150.1
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• 2002

• The Korean Journal of Physiology and Pharmacology
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• 제25권5호
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• pp.495-495
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• 2021

• BMB Reports
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• 제49권2호
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• pp.105-110
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• 2016

Ursodeoxycholic acid (UDCA), a natural, hydrophilic nontoxic bile acid, is clinically effective for treating cholestatic and chronic liver diseases. We investigated the chronic effects of UDCA on age-related lipid homeostasis and underlying molecular mechanisms. Twenty-week-old C57BL/6 male and female mice were fed a diet with or without 0.3% UDCA supplementation for 25 weeks. UDCA significantly reduced weight gain, adiposity, hepatic triglyceride, and hepatic cholesterol without incidental hepatic injury. UDCA-mediated hepatic triglyceride reduction was associated with downregulated hepatic expression of peroxisome proliferator-activated receptor-γ, and of other genes involved in lipogenesis (Chrebp, Acaca, Fasn, Scd1, and Me1) and fatty acid uptake (Ldlr, Cd36). The inflammatory cytokines Tnfa, Ccl2, and Il6 were significantly decreased in liver and/or white adipose tissues of UDCA-fed mice. These data suggest that UDCA exerts beneficial effects on age-related metabolic disorders by lowering the hepatic lipid accumulation, while concurrently reducing hepatocyte and adipocyte susceptibility to inflammatory stimuli.

• Biomolecules & Therapeutics
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• 제23권1호
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• pp.71-76
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• 2015

Peroxisome proliferator-activated receptor gamma ($PPAR{\gamma}$) was identified as a cell-intrinsic regulator of Th17 cell differentiation. Th17 cells have been associated with several autoimmune diseases, including experimental autoimmune encephalomyelitis (EAE), inflammatory bowel disease (IBD), and collagen-induced arthritis. In this study, we confirmed $PPAR{\gamma}$-mediated inhibition of Th17 cell differentiation and cytokine production at an early stage. Treatment with ciglitazone, a $PPAR{\gamma}$ ligand, reduced both IL-$1{\beta}$-mediated enhancement of Th17 differentiation and activation of Th17 cells after polarization. For Th17 cell differentiation, we found that ciglitazone-treated cells had a relatively low proliferative activity and produced a lower amount of cytokines, regardless of the presence of IL-$1{\beta}$. The inhibitory activity of ciglitazone might be due to decrease of CCNB1 expression, which regulates the cell cycle in T cells. Hence, we postulate that a pharmaceutical $PPAR{\gamma}$ activator might be a potent candidate for treatment of Th17-mediated autoimmune disease patients.

• Asian-Australasian Journal of Animal Sciences
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• 제29권2호
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• pp.184-194
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• 2016

The peroxisome proliferator-activated receptor gamma ($PPAR{\gamma}$) gene plays an important role in the biosynthesis process controlled by a number of fatty acid transcription factors. This study investigates the relationships between 130 single-nucleotide polymorphisms (SNPs) in the $PPAR{\gamma}$ gene and the fatty acid composition of muscle fat in the commercial population of Korean native cattle. We identified 38 SNPs and verified relationships between 3 SNPs (g.1159-71208 A>G, g.42555-29812 G>A, and g.72362 G>T) and the fatty acid composition of commercial Korean native cattle (n = 513). Cattle with the AA genotype of g.1159-71208 A>G and the GG genotype of g.42555-29812 G>A and g.72362 G>T had higher levels of monounsaturated fatty acids and carcass traits (p<0.05). The results revealed that the 3 identified SNPs in the $PPAR{\gamma}$ gene affected fatty acid composition and carcass traits, suggesting that these 3 SNPs may improve the flavor and quality of beef in commercial Korean native cattle.

• The Korean Journal of Physiology and Pharmacology
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• 제21권3호
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• pp.317-325
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• 2017

Non-alcoholic fatty liver disease (NAFLD) has become the most prevalent liver disease in parallel with worldwide epidemic of obesity. Reactive oxygen species (ROS) contributes to the development and progression of NAFLD. Peroxisomes play an important role in fatty acid oxidation and ROS homeostasis, and catalase is an antioxidant exclusively expressed in peroxisome. The present study examined the role of endogenous catalase in early stage of NAFLD. 8-week-old male catalase knock-out (CKO) and age-matched C57BL/6J wild type (WT) mice were fed either a normal diet (ND: 18% of total calories from fat) or a high fat diet (HFD: 60% of total calories from fat) for 2 weeks. CKO mice gained body weight faster than WT mice at early period of HFD feeding. Plasma triglyceride and ALT, fasting plasma insulin, as well as liver lipid accumulation, inflammation (F4/80 staining), and oxidative stress (8-oxo-dG staining and nitrotyrosine level) were significantly increased in CKO but not in WT mice at 2 weeks of HFD feeding. While phosphorylation of Akt (Ser473) and $PGC1{\alpha}$ mRNA expression were decreased in both CKO and WT mice at HFD feeding, $GSK3{\beta}$ phosphorylation and Cox4-il mRNA expression in the liver were decreased only in CKO-HF mice. Taken together, the present data demonstrated that endogenous catalase exerted beneficial effects in protecting liver injury including lipid accumulation and inflammation through maintaining liver redox balance from the early stage of HFD-induced metabolic stress.

• Journal of Microbiology and Biotechnology
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• 제25권3호
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• pp.334-342
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• 2015

4-O-Methylhonokiol (MH), a bioactive compound derived from Magnolia officinalis, is known to exhibit antitumor effects in various cancer cells. However, the precise mechanism of its anticancer activity in cervical cancer cells has not yet been studied. In this study, we demonstrated that MH induces apoptosis in SiHa cervical cancer cells by enhancing peroxisome proliferator-activated receptor-gamma (PPARγ) activation, followed by inhibition of the PI3K/Akt pathway and intrinsic pathway induction. MH upregulated PPARγ and PTEN expression levels while it decreased p-Akt in the MH-induced apoptotic process, thereby supporting the fact that MH is a PPARγ activator. Additionally, MH decreased the expression of Bcl-2 and Bcl-XL, inducing the intrinsic pathway in MH-treated SiHa cells. Furthermore, MH treatment led to the activation of caspase-3/caspase-9 and proteolytic cleavage of polyADP ribose polymerase. The expression levels of Fas (CD95) and E6/E7 oncogenes were not altered by MH treatment. Taken together, MH activates PPARγ/PTEN expression and induces apoptosis via suppression of the PI3K/Akt pathway and mitochondria-dependent pathways in SiHa cells. These findings suggest that MH has potential for development as a therapeutic agent for human cervical cancer.

• Asian Pacific Journal of Cancer Prevention
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• 제15권21호
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• pp.9093-9099
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• 2014

A growing body of evidence suggests that the peroxisome proliferator-activated receptor-gamma ($PPAR{\gamma}$) gene may harbor targets for the chemoprevention of breast cancer. However, it is unclear whether polymorphisms in the $PPAR{\gamma}$ gene are associated with the susceptibility of breast cancer. We performed a candidate gene association study between $PPAR{\gamma}$ polymorphisms and breast cancer and a meta-analysis on the association of breast cancer with selected $PPAR{\gamma}$ variants. Six single nucleotide polymorphisms (SNPs) in the $PPAR{\gamma}$ gene were analyzed among 456 breast cancer patients and 461 controls from the National Cancer Center in Korea. Association between the polymorphisms and breast cancer risk were assessed using the Cochrane-Armitage test for trend and a multivariate logistic regression model. Two SNPs, rs3856806 and rs1801282, had been previously analyzed, thus enabling us to perform pooled analyses on their associations with breast cancer susceptibility. Our findings from the candidate gene association study showed no association between the $PPAR{\gamma}$ gene polymorphisms and breast cancer risk. A meta-analysis combining existing studies and our current study also refuted an association of the $PPAR{\gamma}$ gene with breast cancer. Our findings suggest that the $PPAR{\gamma}$ gene may not harbor variants that alter breast cancer susceptibility, although a moderate sample size might have precluded a decisive conclusion.

• Preventive Nutrition and Food Science
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• 제7권4호
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• pp.454-460
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• 2002

While atherosclerosis is a major killer, there is now concern that mortality from the disease will increase due to the rising incidence of type II diabetes. Because diet can potentially influence both diseases, it is important to elucidate the role of diet in the progression of atherosclerosis. In addition, the mechanisms involved in dietary-related alterations of the disease need to be defined to guide public health recommendations to reduce athero-sclerosis incidence and limiting unwanted side effects. Since diet is thought to play a role in atherosclerosis even without added complications due to type II diabetes, reducing the incidence of that metabolic disease will not be enough. While evidence is increasing that high intake of carbohydrate can lead to type II diabetes and atherosclerosis, the preponderance of existing evidence indicates that intake of specific fats as a major dietary causal factor. It has recently been hypothesized that a dietary fat link to atherosclerosis may depend partly on the activity of a transcriptional regulator, the peroxisome proliferator activated receptors (PPAR). Thusfar, PPAR $\alpha$, $\beta$/$\delta$ and ${\gamma}$, have been shown to play a major role in metabolism, inflammation, and cancer. Furthermore, PPAR may regulate specific processes associated with atherosclerosis such as triglyceride and low density lipoprotein (LDL) metabolism; the reverse cholesterol transport pathway; lipid accumulation within plaques; the local inflammatory response and plaque stability. Synthetic ligands for PPAR have been developed; however, natural ligands include specific fatty acids and their metabolites. Though the role of PPAR in atherosclerosis has been reported with respect to synthetic ligands, additional studies need to be done with established and possible natural ligands. In this review, we will focus on the relation of dietary fat to PPAR alteration of atherosclerosis.