• 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.

• Bulletin of the Korean Chemical Society
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• v.33 no.5
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• pp.1475-1479
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• 2012

Human peroxisome proliferator-activated receptor gamma ($hPPAR{\gamma}$) has been implicated in numerous pathologies, including obesity, diabetes, and cancer. In this study, we verified that amentoflavone is an agonist of $hPPAR{\gamma}$ and probed the molecular basis of its action. It was demonstrated that amentoflavone bound $hPPAR{\gamma}$ with high (picomolar) affinity and increased the binding between $hPPAR{\gamma}$ and steroid receptor coactivator-1 (SRC-1) by approximately 4-fold. Based on a docking study, for the first time, we propose a model of amentoflavone and $hPPAR{\gamma}$ binding in which amentoflavone forms three hydrogen bonds with the side chains of His323, Tyr327, and Arg280 in $hPPAR{\gamma}$ and participates in two hydrophobic interactions.

• Biomedical Science Letters
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• v.10 no.2
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• pp.137-142
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• 2004

The peroxisome proliferator-activated receptor $\gamma$ (PPAR${\gamma}$) is the molecular target for a class of drugs, the antidiabetic thiazolidnediones (TZDs). The heterodimer of PPAR${\gamma}$ with retinoid X receptor (RXR) plays a central role in the regulation of adipogenesis and insulin sensitization. We synthesized two chemicals, DANA87 and DANA88, sharing structural characteristics with TZDs. Given this structural similarity, it was hypothesized that DANA87 and DANA88 may act as PPAR$\gamma$ ligands. In transient transfection assays, DANA87 and DANA88 caused slight increases in the endogenous expression of a luciferase reporter gene containing the PPAR responsive element in 3T3-L1 preadipocytes. However, DANA87 and DANA88 significantly inhibited troglitazone-induced reporter gene activation when cells were treated with a combination of DANA87 or DANA 88 and troglitazone, one of the TZDs that activate PPAR$\gamma$. These results suggest that DANA87 and DANA88 are not only weak agonists of PPAR${\gamma}$ transactivation, but also competitively antagonize troglitazone-induced PPAR$\gamma$ reporter activity.

• Biomedical Science Letters
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• v.11 no.1
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• pp.1-8
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• 2005

Fibrates are a class of hypolipidemic agents whose effects are mediated by activation of a specific transcription factor called the peroxisome proliferator-activated receptor $\alpha\;(PPAR\alpha).\;PPAR\alpha$ regulates the pathways of lipid catabolism such as fatty acid oxidation and the triglyceride metabolism, resulting in the treatment of hyperlipidemia. The decreased levels of plasma triglycerides by fibrates are responsible for hypertrophy and hyperpalsia of adipose cells. To determine whether fenofibrate regulates adipogenesis in female C57BL/6J mice, we measured the effects of fenofibrate on not only body weight, adipose tissue mass and serum triglycerides, but also the histology of adipose tissue and the expression of adipocyte marker genes. Fenofibrate did not inhibit high fat diet-induced increases in body weight, adipose tissue mass and serum triglycerides. Furthermore, fenofibrate did not cause the changes in the size and number of adipocytes and the expression of adipocyte-specific genes such as leptin and $TNF\alpha$. Therefore, this study demonstrates that fenofibrate does not affect adipogenesis in female mice.

• Molecules and Cells
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• v.41 no.1
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• pp.55-64
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• 2018

Autophagy is an intracellular degradation pathway for large protein aggregates and damaged organelles. Recent studies have indicated that autophagy targets cargoes through a selective degradation pathway called selective autophagy. Peroxisomes are dynamic organelles that are crucial for health and development. Pexophagy is selective autophagy that targets peroxisomes and is essential for the maintenance of homeostasis of peroxisomes, which is necessary in the prevention of various peroxisome-related disorders. However, the mechanisms by which pexophagy is regulated and the key players that induce and modulate pexophagy are largely unknown. In this review, we focus on our current understanding of how pexophagy is induced and regulated, and the selective adaptors involved in mediating pexophagy. Furthermore, we discuss current findings on the roles of pexophagy in physiological and pathological responses, which provide insight into the clinical relevance of pexophagy regulation. Understanding how pexophagy interacts with various biological functions will provide fundamental insights into the function of pexophagy and facilitate the development of novel therapeutics against peroxisomal dysfunction-related diseases.

• Molecules and Cells
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• v.22 no.2
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• pp.239-245
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• 2006

This study examined whether adult bovine muscle satellite cells from 30-month-old Hanwoo cattle are multipotential. The satellite cells were found to have the potential to proliferate and differentiate into myoblasts with the formation of multinucleated cells. In addition, treatment with the peroxisome proliferator activating receptor-${\gamma}$ ($PPAR{\gamma}$) agonist, rosiglitazone, promoted their trans-differentiation into adipocytes with significant increases in glycerol accumulation and glycerol-3-phosphate dehydrogenase activity. Western blot analysis revealed that increased levels of the adipocyte fatty acid-binding protein, $PPAR{\gamma}$ and of CCAAT/enhancerbinding protein were closely related to rosiglitazoneinduced differentiation of the cells. These findings demonstrate that satellite cells from adult Hanwoo cattle are multipotent, and that their trans-differentiation into adipocytes can be induced by rosiglitazone.

• Journal of Korean Medicine for Obesity Research
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• v.16 no.2
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• pp.109-115
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• 2016

Objectives: The all anti-obesity drugs currently approved by the US Food and Drug Administration work by reducing energy intake. In fact, no approved drug targets energy expenditure. In Korean medicine, it is known to Qi or Yang invigorating therapy could increase energy metabolism. Aconitum carmichaeli Debx (ACD) is a Yang invigorating herb, often used for treat obesity in Korean medicine. In the present study, the authors investigated the regulatory effects of ACD in energy metabolism and mitochondrial biogenesis in C2C12 skeletal muscle cells. Methods: The water extract of ACD (0.2, 0.5 and 1.0 mg/ml) were treated in differentiated C2C12 cells. The protein or mRNA levels of target genes were analyzed and mitochondrial mass were investigated. Results: ACD activated the expressions of peroxisome proliferator-activated receptor gamma coactivator 1-alpha ($PGC-1{\alpha}$), nuclear respiratory factor 1 and TFAM and increased mitochondrial mass. ACD also increased adenosin monophosphate-activated protein kinase (AMPK), and acetyl-CoA carboxylase. Conclusions: This study suggests that ACD has the potential to increase energy metabolism and mitochondrial biogenesis by activating AMPK and $PGC1{\alpha}$.

• Molecules and Cells
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• v.24 no.2
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• pp.167-176
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• 2007

Peroxisome proliferator-activated receptor-gamma ($PPAR{\gamma}$) is expressed at very high levels in the gastrointestinal epithelium. Many of the functions of $PPAR{\gamma}$ in gastrointestinal epithelial cells have been elucidated in recent years, and a pattern is emerging which suggests that this receptor plays an important role in gastrointestinal physiology. There is also strong evidence that $PPAR{\gamma}$ is a colon cancer suppressor in pre-clinical rodent models of sporadic colon cancer, and there is considerable interest in exploitation of $PPAR{\gamma}$ agonists as prophylactic or chemopreventive agents in colon cancer. Studies in mice and in human colon cancer cell lines suggest several mechanisms that might account for the tumor suppressive effects of $PPAR{\gamma}$ agonists, although it is not in all cases clear whether these effects are altogether mediated by $PPAR{\gamma}$. Conversely, several reports suggest that $PPAR{\gamma}$ agonists may promote colon cancer under certain circumstances. This possibility warrants considerable attention since several million individuals with type II diabetes are currently taking $PPAR{\gamma}$ agonists. This review will focus on recent data related to four critical questions: what is the physiological function of $PPAR{\gamma}$ in gastrointestinal epithelial cells; how does $PPAR{\gamma}$ suppress colon carcinogenesis; is $PPAR{\gamma}$ a tumor promoter; and what is the future of $PPAR{\gamma}$ in colon cancer prevention?

• Journal of Applied Biological Chemistry
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• v.60 no.1
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• pp.23-28
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• 2017

Amomum tsao-ko used as a traditional oriental herbal medicine, is indigenous to several Asia countries. In this study, we investigated anti-obesity activity of the ethanol extract of Amomum Taso-ko (A. tsao-ko). The ethanol extract of A. tsao-ko inhibited adipocyte differentiation using Oil Red O assay in 3T3-L1 cells. Inhibitory effect of the ethanol extract of A. tsao-ko on adipogenesis was modulated by down-regulation adipogenic transcriptional factor such as peroxisome proliferator-activated receptor ${\gamma}$ ($PPAR{\gamma}$), CCAAT-enhancer-binding protein ${\alpha}$ ($C/EBP{\alpha}$) and suppressed expression of fatty acid synthase, aP2, and resistin. We demonstrated that A. tsao-ko significantly inhibited adipogenesis and reduced $PPAR{\gamma}$ and $C/EBP{\alpha}$ expression in a dose-dependent manner. These results suggest that A. tsao-ko has an anti-obesity effect by inhibition of adipogenic transcription factor and adipocyte-specific genes in 3T3-L1 cells.