• 대한약학회:학술대회논문집
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• 대한약학회 2003년도 Proceedings of the Convention of the Pharmaceutical Society of Korea Vol.2-1
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• pp.75-78
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• 2003

Polyketides are a class of structurally diverse natural products which possess a wide range of biological activities. These compounds are used throughout medicine and agriculture as antimicrobials, immunosuppressants, antiparasitics, and anticancer agents. While structurally diverse, polyketides are assembled by a common mechanism of decarboxylative condensations of simple malonate derivatives by polyketide synthases (PKSs) in a manner very similar to fatty acid biosynthesis (Fig 1). (omitted)

• 분석과학
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• 제5권4호
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• pp.477-484
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• 1992

형질 전환된 사철느타리버섯으로부터 초원심분리 및 설탕밀도 기울기법으로 44% 층에서 미토콘드리아를 분리정제하였다. ATPase와 ATP synthase의 최적 활성조건은 각각 pH 7.4, $60^{\circ}C$ 및 pH 7.5, $57^{\circ}C$였고, km값은 11.6mM과 8.4mM였다. ATPase는 기질농도 5~6mM의 ATP에서, ATP synthase는 5~10mM ADP 농도에서 활성이 높으며, 그 이상의 농도에서는 기질 저해를 받았다. ATPase/ATP synthase 모두 $Mg^{2+}$ 의존성 효소로 $G_{418}$으로 비경쟁적인 저해를 받았다. 효소의 아미노산 분석결과 hydrophobic 아미노산 잔기는 50.5%, small 아미노산 잔기는 56.1%, hydrogen bonding 아미노산 잔기는 43.7%, helix breaking 아미노산 잔기는 55.2%였다. 인지질을 분석한 결과 phosphatidyl glycerol, phosphatidyl choline 및 phosphatidyl ethanolamine으로 구성되었고 phosphatidyl serine과 phosphatidyl inositol은 전혀 없었다. 포화 지방산은 palmitate(51.31%)와 stearate(18.32%)의 함량이 많았고, 불포화 지방산($C_{18:1}$, $C_{18:2}$ 및 $C_{16:1}$)의 함량도 많았다.

• 대한화장품학회:학술대회논문집
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• 대한화장품학회 2003년도 IFSCC Conference Proceeding Book I
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• pp.440-447
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• 2003

Up until today, the key to contouring has been resumed in these two alternatives, either limiting the adipocyte storing capacity by modulating lipogenesis, or by stimulating lipolysis to eliminate adipocyte lipid content. Another interesting way could be the regulation of adipocyte differentiation. In this work, we have evaluated the effect of a brown algal extract of Sphacelaria scoparia (SSE) on the differentiation of pre-adipocytes into adipocytes. A pre-adipocyte line (3T3-L 1) was used. The differentiation was evaluated by the measure of produced lipids thanks to red oil coloration and spectrophotometry, and also by the expression of adipocyte differentiation markers: enzymes such as fatty acid synthase (FAS) and stearoyl CoA desaturase (SCD), or membrane proteins such as glucose transporters (GLUT -4) and fatty acid transporters (FAT) expressed on the surface of human adipocytes. These genes are under control of two transcription factors: CAAT-enhancer binding protein (c/EBP alpha) and sterol response element binding protein (SREBP1). All these markers were analysed at different stages of differentiation by RT -PCR. Sphacelaria extract (SSE) inhibits pre-adipocytes differentiating into adipocytes following a dose-dependant relation, using a kinetics similar to retinoic acid. It decreases the expression of mRNA specific to FAS, FAT, GLUT -4, SCD1, c/EBP alpha and SREBP1. Moreover, SSE regulated on collagen 1 and collagen 4 expression. A stimulation of collagen 1 was also measured in human skin fibroblasts. Thus, SSE performs as a genuine differentiation inhibitor and not only as a lipogenesis inhibitor, and could be used in slimming products.

• Nutrition Research and Practice
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• 제14권6호
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• pp.568-579
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• 2020

BACKGROUD/OBJECTIVES: Hepatic steatosis is the most common liver disorder, particularly in postmenopausal women. This study investigated the protective effects of standardized rice bran extract (RBS) on ovariectomized (OVX)-induced hepatic steatosis in rats. MATERIALS/METHODS: HepG2 cells were incubated with 200 µM oleic acid to induce lipid accumulation with or without RBS and γ-oryzanol. OVX rats were separated into three groups and fed a normal diet (ND) or the ND containing 17β-estradiol (E2; 10 ㎍/kg) and RBS (500 mg/kg) for 16 weeks. RESULTS: RBS supplementation improved serum triglyceride and free fatty acid levels in OVX rats. Histological analysis showed that RBS significantly attenuated hepatic fat accumulation and decreased hepatic lipid, total cholesterol, and triglyceride levels. Additionally, RBS suppressed the estrogen deficiency-induced upregulation of lipogenic genes, such as sterol regulatory element-binding protein 1 (SREBP1), acetyl-CoA carboxylase 1, fatty acid synthase, glycerol-3-phosphate acyltransferase, and stearoyl-CoA desaturase 1. CONCLUSIONS: RBS and γ-oryzanol effectively reduced lipid accumulation in a HepG2 cell hepatic steatosis model. RBS improves OVX-induced hepatic steatosis by regulating the SREBP1-mediated activation of lipogenic genes, suggesting the benefits of RBS in preventing fatty liver in postmenopausal women.

• 생명과학회지
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• 제32권7호
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• pp.542-549
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• 2022

Polymethoxyflavones (PMFs)는 주로 감귤류에서 발견되는 플라보노이드로 다양한 생리활성을 나타낸다고 알려져 있다. 본 연구에서는 제주재래귤인 진귤(Citrus sunki Hort. ex Tanaka)에서 PMFs를 다량 함유하는 분획물(PMFs-rich fraction, PRF)을 획득하는 방법을 확립하여 3T3-L1 세포에서 지방대사에 미치는 영향을 분석하였다. PRF는 3T3-L1 전구지방세포의 지방생성(lipogenesis)을 농도 의존적으로 억제하였다. PRF는 peroxisome proliferator-activated receptor 𝛾 (PPAR𝛾)와 CCAAT/enhancer binding protein 𝛼 (CEBP𝛼) 발현을 억제함으로써 fatty acid synthase (FAS), adipocyte fatty-acid-binding protein 2 (aP2)의 발현을 억제하여 지방생성을 억제함을 확인할 수 있었다. 성숙한 3T3-L1 지방세포에 PRF를 처리하면, cAMP 의존성 protein kinase A (PKA)/sterol regulatory element-binding protein 1 (HSL)의 활성화가 일어나 지방분해(lipogenesis)는 촉진됨을 확인할 수 있었다. 그리고 PRF는 AMP-activated protein kinase (AMPK)/acetyl-CoA carboxylase (ACC)의 인산화를 증가시켜 지방산화를 촉진할 수 있음을 확인하였다. 이 연구결과는 진귤 잎 유래 PRF는 3T3-L1 전구지방세포의 분화를 억제하고 성숙한 지방세포에서 지방분해 및 지방산 산화를 촉진하는 활성을 나타내어 항비만 소재로서의 활용가능성을 제시하였다.

• 대한한의학방제학회지
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• 제24권2호
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• pp.100-107
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• 2016

Objectives : The purpose of this study is to evaluate the anti-lipogenic effect of Sobuncheong-eum on non-alcoholic fatty liver disease in free fatty acid induced cellular model. Methods : HepG2 cells were treated with palmitate for 24h to overload intracellular triglyceride (TG) content in the presence or absence of Sobuncheong-eum extract. After palmitate treatment, Intracellular TG content was measured with TG assay kit. Several lipogenesis related markers, including AMP-activated protein kinase (AMPK), sterol regulatory element-binding transcription factor-1c (SREBP-1c), acetyl-CoA carboxylase (ACC), and fatty acid synthase (FAS), were assessed using Western-blot analyses and RT-PCR. Results : Palmitate markedly increased intracellular TG in HepG2 cells, and which were alleviated by coadministered Sobuncheong-eum extract. Sobuncheong-eum extract activated AMPK, which plays a key role in reducing hepatic lipid accumulation, and reduced lipogenic fators, SREBP-1c, ACC, and FAS. Conclusions : Taken together, it is conceivable that Sobuncheong-eum has an potential to alleviate steatosis, and which may be mediated by activating AMPK at least in part.

• 대한한방내과학회지
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• 제39권3호
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• pp.302-312
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• 2018

Objectives: This study was performed to investigate the effects of two herbal medicines, Agastachis Herba and Lysimachiae Herba, on a cellular model of non-alcoholic fatty liver diseases (NFLDs). Methods: HepG2 cells were treated with palmitic acid and with various concentrations of Agastachis Herba (AH) or Lysimachiae Herba (LH) extract in water. The lipotoxicity was assessed using EZ-cytox, and the lipoapoptosis was assessed using cell death detection ELISA. Intracellular lipids were measured by oil red O staining. The efficacy of AH and LH on sterol regulatory element-binding transcription factor-1c (SREBP-1c), fatty acid synthase (FAS), and acetyl-CoA carboxylase (ACC) in HepG2 cells was measured by reverse transcription polymerase chain reaction (RT-PCR). Results: Both AH and LH extracts increased lipoapoptosis and decreased lipotoxicity and levels of SREBP-1c, ACC, and FAS (SREBP-1c, ACC, and FAS are factors in lipid synthesis). In the oil red O staining experiment, both extracts also reduced intracellular lipid accumulation; in this instance, LH's efficacy was superior to that of AH. Conclusions: According to the results, both AH and LH are likely to contribute to non-alcoholic fatty liver disease, as both interfere with lipid synthesis.

• Asian Pacific Journal of Cancer Prevention
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• 제16권16호
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• pp.6851-6855
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• 2015

Background: This study aimed to examine the clinical significance of fatty acid synthase (FASN) expression in gastric cancer (GC), and investigate any prognostic role. Materials and Methods: FASN expression was assessed in gastric cancers by immunohistochemistry using 60 paraffin-embedded tissue specimens, and clinical data were collected by retrospective chart review. Moreover, FASN mRNA expression in 15 fresh resected specimens was evaluated by the reverse transcription-polymerase chain reaction (RT-PCR). Immunohistochemical staining of PTEN was performed to assess the correlation of PTEN with FASN in gastric cancer. Results: Increased expression of FASN was noted in gastric cancers. The frequency of FASN gene amplification was also significantly higher in gastric cancer than in adjacent normal tissue. FASN expression in human gastric cancer tissues was significantly correlated with patient TNM stage and peritoneal dissemination (p<0.05). Moreover, higher FASN expression significantly correlated with shorter overall survival (p<0.05). Here, upregulation of FASN negatively correlated with PTEN expression in gastric cancer. Conclusions: These findings indicate that FASN expression is upregulated in gastric cancer, and increased FASN may be critical to th peritoneal metastasis and survival. Our results suggest that FASN upregulation and PTEN downregualtion may be involved in peritoneal dissemination for gastric cancer progression.

• Bulletin of the Korean Chemical Society
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• 제32권8호
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• pp.2695-2699
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• 2011

${\beta}$ Ketoacyl acyl carrier protein synthase III (KAS III) initiates fatty acid synthesis in bacteria and is a key target enzyme to overcome the antibiotic resistance problem. In our previous study, we found flavonoid inhibitors of Enterococcus faecalis KAS III and proposed three potent antimicrobial flavonoids against Enterococcus faecalis and Vancomycin-resistant Enterococcus faecalis with MIC values in the range of 128-512 ${\mu}g/mL$ as well as high binding affinities on the order from $10^6$ to $10^7\;M^{-1}$. Using these series of flavonoids, we conducted biological assays as well as docking study to find potent flavonoids inhibitors of Staphylococcus aureus KAS III with specificities against Staphylococcus aureus and Methicillin-resistant Staphylococcus aureus. Here, we propose that naringenin (5,7,4'-trihydroxyflavanone) and eriodictyol (5,7,3',4'-tetrahydroxyflavanone) are potent antimicrobial inhibitors of Staphylococcus aureus KAS III with binding affinity of $3.35{\times}10^5$ and $2.01{\times}10^5\;M^{-1}$, respectively. Since Arg38 in efKAS III is replaced with Met36 in saKAS III, this key difference caused one hydrogen bond missing in saKAS III compared with efKAS III, resulting in slight discrepancy in their binding interactions as well as decrease in binding affinities. 4'-OH and 7-OH of these flavonoids participated in hydrogen bonding interactions with backbone carbonyl of Phe298 and Ser152, respectively. In particular, these flavonoids display potent antimicrobial activities against various MRSA strains in the range of 64 to 128 ${\mu}M$ with good binding affinities.

• Asian Pacific Journal of Cancer Prevention
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• 제15권18호
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• pp.7617-7623
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• 2014

Objective: The mechanism of action of fatty acid synthase (FASN) in drug tolerance of breast cancer cells with epithelial-mesenchymal transition (EMT) features was investigated. Methods: The breast cancer cell line MCF-7-MEK5 with stably occurring EMT and tumour necrosis factor-${\alpha}$ (TNF-${\alpha}$) tolerance was used as the experimental model, whereas MCF-7 acted as the control. Tumour cells were implanted into nude mice for in vivo analysis, and cerulenin was used as a FASN inhibitor. RT-PCR, real-time quantitative PCR and Western blot were employed to detect the expression of FASN, TNFR-1, TNFR-2, Wnt-1, ${\beta}$-catenin and cytC at the RNA and protein levels. Results: Compared with MCF-7, TNFR-1 expression in MCF-7-MEK5 was slightly changed, TNFR-2 was decreased, and FASN, Wnt-1, ${\beta}$-catenin and cytC were increased. The expression of Wnt-1 and ${\beta}$-catenin in MCF-7-MEK5 decreased after cerulenin treatment, whereas cytC expression increased. Conclusions: The important function of FASN in the drug tolerance of breast cancer may be due to the following mechanisms: FASN downregulated TNFR-2 expression through lipid rafts to make the cells less sensitive to TNF-${\alpha}$, and simultaneously activated the Wnt-$1/{\beta}$-catenin signalling pathway. Thus, cytC expression increased, which provided cells with anti-apoptotic capacity and induced drug tolerance.