• 생명과학회지
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• 제24권5호
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• pp.476-484
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• 2014

비만은 감염원 없이 진행되는 낮은 수준의 만성적인 전신성 염증상태로 간주되며, 만성대사질환의 원인이 된다. 본 연구에서는 미나리를 발효하여 만든 식초가 3T3-L1 지방전구세포의 분화 및 RAW 264.7 세포에서의 항염증 효과에 미치는 영향을 확인하였다. MDI (IBMX, dexamethasone, insulin)에 의해 분화가 유발된 3T3-L1 지방전구세포에 대한 미나리 식초의 분화 억제능을 Oil-red-O staining을 통해 확인하였으며, western blot법을 통해 지방세포 형성 시 중요한 전사인자인 peroxisome proliferator-activated receptor-${\gamma}$ (PPAR-${\gamma}$)와 CCAAT-enhancer-binding protein ${\alpha}$ ($C/EBP{\alpha}$)의 발현을 감소시키는 것으로 나타났다. 또한, 미나리 식초가 lipopolysaccharide (LPS)에 의해 염증이 유발 된 RAW 264.7 세포의 nitric oxide (NO) 생성을 억제시켰으며, inducible NO synthase (iNOS)와 cyclooxygenase-2 (COX-2)의 단백질 발현을 감소시키는 것을 확인하였다. 이러한 결과들을 통해 미나리 발효 식초는 지방세포 분화와 염증 억제 효과를 가지고 있음을 확인하였다. 따라서 미나리 발효 식초는 대사성 질환을 예방할 수 있는 천연물 소재로 이용 가능할 것으로 생각된다.

• BMB Reports
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• 제47권11호
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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 $PPAR{\gamma}$.

• 생명과학회지
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• 제22권12호
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• pp.1688-1696
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• 2012

돌미나리(Oenanthe javanica)는 뛰어난 해독작용과 항균작용으로 예로부터 약재로 사용되어 왔으나 돌미나리씨의 활성은 아직 밝혀지지 않았다. 본 연구에서는 3T3-L1 지방전구세포를 사용하여 돌미나리씨 메탄올 추출물(OJSE)의 지방세포분화에 미치는 영향과 그 기전에 대해 조사하였다. 세포독성이 없는 농도($1{\sim}200{\mu}g/ml$)의 OJSE를 지방세포 분화유도제와 동시에 지방전구세포에 처리하여 분화시킨 후 Oil Red O 염색을 한 결과 세포내 lipid droplet 생성 및 triglyceride 축적이 OJSE 농도의존적으로 감소되었으며, 지방세포분화과정에 중요한 역할을 하는 지방세포특이적 마커인 CCAAT/enhancer binding proteins ${\alpha}$, ${\beta}$ ($C/EBP{\alpha}$, $C/EBP{\beta}$) 및 peroxisome proliferator-activated receptor ${\gamma}$ ($PPAR{\gamma}$)의 발현이 현저하게 저하되었다. 이는 OJSE에 의해 지방세포 분화 관련 전사인자의 발현이 효과적으로 억제되어 지방세포로의 분화가 저해되고 결과적으로 지방세포내 lipid droplet 생성 및 triglyceride 축적이 억제되었다는 것을 시사한다. 또한 OJSE처리에 의해 mitotic clonal expanstion 단계에서의 세포증식이 저해되었으며, 세포주기의 변화를 분석한 결과, OJSE처리에 의해 지방전구세포의 G1 arrest가 유발됨을 확인하였다. 세포주기 관련 단백질 발현을 분석한 결과, OJSE 농도의존적으로 Cdk inhibitor인 p21의 발현이 현저하게 증가되었으며, 반면 cyclin E, Cdk2, E2F-1 및 phospho-Rb의 발현은 저하됨을 알 수 있었다. 이러한 연구 결과들에 의해 OJSE는 지방전구세포의 G1 arrest를 유도하고 지방세포분화 관련 단백질의 발현을 억제하여 지방세포로의 분화를 억제하는 항비만 효능을 갖는 천연 소재임을 확인하였고, 본 연구는 이를 활용한 향후 지속적인 연구를 위한 기초자료로 그 가치가 매우 높을 것으로 생각된다.

• 생약학회지
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• 제45권3호
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• pp.194-199
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• 2014

The roots of Paeonia lactiflora (PL) has been traditionally used as analgesic, spasmolytic and tonic in Korea, China, and Japan. As part of a search for herbal medicine to treat diabetes and obesity, we confirmed hypoglycemic effect of PL through high fat diet-induced obese and diabetic mice experiments in vivo. Treatment of ethanolic extract from PL led to a significant decrease in glucose level, which is comparable to that of an antidiabetic drug metformin. In addition, PL selectively stimulates the transcriptional activities of both peroxisome proliferator-activated receptor $(PPAR){\alpha}$ and ${\gamma}$, and inhibits enzymatic activity of protein tyrosine phosphatase 1B (PTP1B), which are predicted to be therapeutic target in treatment of type2 diabetes and obesity. Especially, the n-hexane fraction (Hx) from PL ethanol extract showed more potent activities on $PPAR{\alpha}$ and than others and exihibited moderate inhibitory activity against PTP1B.

• 대한의생명과학회지
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• 제20권2호
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• pp.62-69
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• 2014

Previous our study demonstrated that ailanthoidol (3-deformylated 2-arylbenzo[b]furan), a neolignan from Zanthoxylum ailanthoides or Salvia miltiorrhiza Bunge, is a novel anti-inflammatory agent. In this investigation, we examined the anti-adipogenic effect of ailanthoidol. Our data showed that ailanthoidol suppressed lipid droplet formation and adipocyte differentiation in 3T3-L1 cells. Treatment of the 3T3-L1 adipocytes with ailanthoidol resulted in an attenuation of the releases of leptin and interleukin-6. The expression of peroxisome proliferator-activated receptor $(PPAR){\gamma}$ and CCAAT/enhancer-binding protein $(C/EBP){\alpha}$, the central transcriptional regulators of adipogenesis, was decreased by treatment with ailanthoidol. Additionally, ailanthoidol treatment increased the phosphorylation levels of 5' adenosine monophosphate-activated protein kinase. These results suggest that ailanthoidol effectively suppresses adipogenesis and that it exerts its role mainly through the significant down-regulation of $PPAR{\gamma}$ and $C/EBP{\alpha}$ expression. Our findings provide important insights into the mechanisms underlying the anti-adipogenic activity of ailanthoidol.

• Natural Product Sciences
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• 제28권2호
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• pp.80-88
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• 2022

Colorectal cancer is one of the most common cancers globally, ranking second for the number of cancer-related deaths. Metastasis has been reported as the main cause of death in patients with colorectal cancer. Peroxisome proliferator-activated receptor gamma (PPAR-γ) is a transcription factor that functions as a tumor suppressor by inhibiting cellular proliferation, migration, and invasion. In our previous efforts to generate natural product-motivated PPAR-γ ligands, the compounds 1 and 2 were obtained. These compounds activated PPAR-γ and inhibited the migration and invasion of HCT116 colorectal cancer cells, and they were also found to inhibit the epithelial-to-mesenchymal transition, which is a key process in cancer metastasis. Compounds 1 and 2 upregulated expression of the epithelial marker (E-cadherin), and downregulated expression of the mesenchymal marker (N-cadherin) and transcriptional factor (Snail). Therefore, the PPAR-γ agonists 1 and 2 could serve as a valuable model for the study on anti-metastatic leads for the treatment of colorectal cancer.

• Preventive Nutrition and Food Science
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• 제11권4호
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• pp.285-288
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• 2006

The anti-adipogenic effect of dongchimi nano juice prepared using a nano-filtering process was investigated by measuring leptin and glycerol levels and the expression of a peroxisome proliferator-activated $receptor-\gamma\;(PPAR\gamma)$ gene as indicators of lipid accumulation or lipolysis. Red pepper powder, seeds of red pepper, garlic, and ginger were added in the preparation of dongchimi. Dongchimi was fermented to reach the optimal fermentation period, followed by nano-filtration in the range of $0.0005\sim0.1\;{\mu}m$. The lactic acid bacteria of dongchimi nano juice were removed completely by a nano-filtering process. Treatment of dongchimi nano juice induced glycerol release in the 3T3-L1 adipocytes and decreased the mRNA expression level of $PPAR\gamma$. These results suggested that dongchimi nano juice may enhance lipolysis and modulate adipogenesis in 3T3-L1 cells.

• 한국발생생물학회지:발생과생식
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• 제22권4호
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• pp.351-360
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• 2018

The adipogenesis is a maturation process of pre-adipocyte cell into mature lipid-filled adipocyte cell. The adipogenesis begins at the late prenatal stage and continues until the early postnatal age. Because the adipogenesis and formation of adipose tissue persist during postnatal period and are precisely regulated by the action of numerous gene products, the present research was attempted to determine the expressional patterns of adipose tissue-associated genes in the rat epididymal fat pad at different postnatal ages, from 7 days to 2 years of ages, using a quantitative real-time PCR analysis. The basal expression levels of CCAAT/enhancer binding protein gamma, sterol regulatory element binding transcription factor 1, fatty acid binding protein 4, adiponectin, leptin, and resistin at the early postnatal ages were significantly lower than those at the elderly ages, even though a fluctuation of expressional levels was observed at some ages. The lowest expressional level of delta like non-canonical Notch ligand 1 was detected at 44 days and 5 months of ages. The expression of peroxisome proliferator-activated receptor gamma ($PPAR{\gamma}$) was the highest at 44 days of age, followed by a diminished expression of $PPAR{\gamma}$ at the elderly ages. These results indicate the existence of a complex regulatory mechanism(s) for expression of adipose tissueassociated genes in the rat epididymal fat during postnatal period.

• Molecules and Cells
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• 제39권2호
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• pp.87-95
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• 2016

Sirt1 is the most prominent and extensively studied member of sirtuins, the family of mammalian class III histone deacetylases heavily implicated in health span and longevity. Although primarily a nuclear protein, Sirt1's deacetylation of Peroxisome proliferator-activated receptor Gamma Coactivator-$1{\alpha}$ (PGC-$1{\alpha}$) has been extensively implicated in metabolic control and mitochondrial biogenesis, which was proposed to partially underlie Sirt1's role in caloric restriction and impacts on longevity. The notion of Sirt1's regulation of PGC-$1{\alpha}$ activity and its role in mitochondrial biogenesis has, however, been controversial. Interestingly, Sirt1 also appears to be important for the turnover of defective mitochondria by mitophagy. I discuss here evidences for Sirt1's regulation of mitochondrial biogenesis and turnover, in relation to PGC-$1{\alpha}$ deacetylation and various aspects of cellular physiology and disease.

• Nutrition Research and Practice
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• 제16권1호
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• pp.14-32
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• 2022

BACKGROUND/OBJECTIVES: Peroxisome proliferator-activated receptor-gamma co-activator-1α (PGC-1α) has a central role in regulating muscle differentiation and mitochondrial metabolism. PGC-1α stimulates muscle growth and muscle fiber remodeling, concomitantly regulating lactate and lipid metabolism and promoting oxidative metabolism. Gynostemma pentaphyllum (Thumb.) has been widely employed as a traditional herbal medicine and possesses antioxidant, anti-obesity, anti-inflammatory, hypolipemic, hypoglycemic, and anticancer properties. We investigated whether G. pentaphyllum extract (GPE) and its active compound, gypenoside L (GL), affect muscle differentiation and mitochondrial metabolism via activation of the PGC-1α pathway in murine C2C12 myoblast cells. MATERIALS/METHODS: C2C12 cells were treated with GPE and GL, and quantitative reverse transcription polymerase chain reaction and western blot were used to analyze the mRNA and protein expression levels. Myh1 was determined using immunocytochemistry. Mitochondrial reactive oxygen species generation was measured using the 2'7'-dichlorofluorescein diacetate assay. RESULTS: GPE and GL promoted the differentiation of myoblasts into myotubes and elevated mRNA and protein expression levels of Myh1 (type IIx). GPE and GL also significantly increased the mRNA expression levels of the PGC-1α gene (Ppargc1a), lactate metabolism-regulatory genes (Esrra and Mct1), adipocyte-browning gene fibronectin type III domain-containing 5 gene (Fndc5), glycogen synthase gene (Gys), and lipid metabolism gene carnitine palmitoyltransferase 1b gene (Cpt1b). Moreover, GPE and GL induced the phosphorylation of AMP-activated protein kinase, p38, sirtuin1, and deacetylated PGC-1α. We also observed that treatment with GPE and GL significantly stimulated the expression of genes associated with the anti-oxidative stress response, such as Ucp2, Ucp3, Nrf2, and Sod2. CONCLUSIONS: The results indicated that GPE and GL enhance exercise performance by promoting myotube differentiation and mitochondrial metabolism through the upregulation of PGC-1α in C2C12 skeletal muscle.