• Journal of Nutrition and Health
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• 제19권5호
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• pp.296-303
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• 1986

흰쥐의 lipoprotein을 제거한 혈장내의 지질전이 활성도와 지진전이를 저해하는 활성도를 측정하였다. 지질전이 활성도의 측정은 방사성 동위원소가 함유된 cholesteryl ester (CE)와 triglyceride (TG) 로 표지된 인체의 혈장 low density lipoprotein 으로부터 high high density lipoprotein(HDL) 으로 전이되는 방사성 동위원소의 양을 측정하여 계산하였다. 지질전이 저해 활성도는 정제한 인체 혈장 지질전이 단백질에 의한 지질전이를 저해하는 정도로서 측정하였다. 흰쥐의 혈장에는 지질전이 활성도가 거의 없으나, 지질전이를 저해하는 활성도는 존재하였다. 지질전이 저해정도는 측정용액내의 lipoprotein 양이 증가할수록 감소하였다. 일반적으로 흰쥐의 HDL은 인체의 HDL에 비하여 CE 의 함량은 높으며 TG의 함량은 낮다. 흰쥐의 혈장에 인체의 혈장으로부터 정제한 지질전이 단백질을 가하여 37$^{\circ}C$에 24시간 두었을 때, HDL 로부터 very low density lipoprotein (VLDL)으로 CE가 이동하여 VLDL 의 CE 함량이 4배나 증가하였다. 반면에 VLDL로부터 HDL$_2$로TG가 이동하여 $HDL_2$의 함량은 TG함량은 9배나 증가하였다. 이와같은 현상은 흰쥐의 혈장 Lipoportein이 지질전이의 기질로서의 결함은 없음을 보여준다. 따라서 지질대사에 관한 실험에서의 흰쥐에 의한 실험결과의 해석에는 인체 혈장에 비하여 혈장에는 lipoprotein사이의 중성지질의 전이나 교환이 거의 없다는 특성이 고려되어야한다.

• Preventive Nutrition and Food Science
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• 제1권1호
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• pp.87-92
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• 1996

This study describes a stable and simple method for the measurement of cholesteryl ester transfer protein(CETP) activities using reconstituted HDL and LDL as substrates. Apolipoproteins (apo) A-I and -B were purified from hog plasma by a new strategy without ultracentrifugation and delipidation. a simple two-step column chromatography was administered. In the first step of phenyl-sepharose CL-4B column chro-matography, hydrophobic plasma proteins were isolated. The most hydrophobic proteins bound to the column appeared to be A-I and apo-B. Contaminat proteins were efficiently eliminated from the sample by washing the column with 0.3M NaCI containing buffer after loading the plasma on the column. Two pure proteins showing each single band on SDS-PSGE of apo A-I and apo-B were individually obtained by a subsequent gel filtration column chromatography(Sephadex G-200). This two-step purification was simple and inexpensive compared to the ultracentrifugation and/or delipidation method that are most commonly used. Reconstituted hight-density lipoproteins(HDL) and low-density lipoproteins(LDL) were prepared using the purified apo A-I and-B, respectively. When these artificially prepared HDL and LDL were used in the assays for CETP as the cholesteryl ester(CE) donor and acceptor respectively, the specific transfer of CE increased up to two fold compared to that used the native HSL and LDL.

• 생약학회지
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• 제31권2호
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• pp.149-156
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• 2000

Atherosclerosis is emerging as one of the major causes of death in Korea as well as Western societies. In the present study; hypocholesterolemic and antiatherogenic effects of the ethanol extract of Allium victorialis Makino was investigated using the conventional rabbit and the cholesteryl ester transfer protein (CETP)-transgenic mouse model. Hypercholesterolemia was induced by feeding high cholesterol diet to the animals for 30 days and they were then fed with high cholesterol diet containing 0.5% of the A. victorialis extract for additional 30 (or 40) days. In the experiment using rabbits, treatment with the A. victorialis extract significantly decreased plasma total cholesterol, low density lipoprotein (LDL)-cholesterol, triglyceride levels and lipid peroxidation compared to those in the control group. Total cholesterol contents in the liver and the heart were also significantly decreased. Lipid staining of the aorta isolated from the rabbits showed that treatment with the A. victorialis extract decreased formation of atheromatous plaques on the intima of the aorta. In the experiment employing CETP transgenic mouse model, treatment with the A. victorialis extract decreased the levels of plasma total cholesterol and the tissue triglyceride levels in the heart. These results demonstrated that the ethanol extract of A. victorialis lowered serum cholesterol levels, tissue lipid contents and accumulation of cholesterol in the artery.

• Journal of Nutrition and Health
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• 제26권7호
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• pp.819-828
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• 1993

Lecithin Cholesterol Acyltransferase(LCAT)와 cholesteryl ester transfer protein(CETP)은 간과 간외조직간의 혈청 cholcsterol 항상성을 유지하는데 중요한 기전인 reverse cholestrol transport system(RCT)에 매우 중요한 인자들이다. 본 연구의 목적은 RCT 기전의 식이 지질 효과를 추정하여 항 고지혈증 치료식이 연구의 중요한 자료를 제공하는데 있다. 4주의 인체대사 실험에서, 새당사 12명의 여성들은 실험 1주 전에 고 포화지질로써 적응시기를 거친 후, 각각 6명씩 high PUFA(corn oil)군과 high SFA(butter)군에 무작위로 배정되었다. Butter군은 total-34(%), esterified-(96%), $HDL_3$-(23%), LDL-(20%) 및 VLDL+LDL-(35%) cholestetol을 감소시켰다. Corn oil군은 esterified(2.5%) 및 LDL-(15%) cholesterol과 triglycerde(27%)를 감소시켰다. Corn oil과 butter fat군간의 식이 효과 차이는 total-(p=0.0001), esterified-(p=0.0001), total HDL-(p=0.005), $HDL_2$-(p=0.01) 및 LDL-(p=0.0001) cholesterol에서 유의적이다. LCAT activity는 두 군에서 변화가 없으나, 4주 후 CETP activity는 butter군에서 2.5배 증가하였다. 이는 VLDL+LDL cholesterol 농도가 butter군에서 증가한 결과와 일치한다. LCAT activity는 corn oil군에서 증가된 HDL의 apo A-I 농도와 free cholesterol과 정의 상관관계가 높은 반면, CETP activity는 total cholesterol과 LDL 및 VLDL+LDL cholesterol과 정의 상관관계가 높았다.

• Molecules and Cells
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• 제26권4호
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• pp.409-414
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• 2008

The cholesteryl ester transfer protein (CETP), a key player in cholesterol metabolism, has been shown to promote the transfer of triglycerides from very low density lipoprotein (VLDL) and low density lipoprotein (LDL) to high density lipoprotein (HDL) in exchange for cholesterol ester. Here we demonstrate that farnesoid X receptor ${\alpha}$ ($FXR{\alpha}$; NR1H4) down-regulates CETP expression in HepG2 cells. A $FXR{\alpha}$ ligand, chenodeoxycholic acid (CDCA), suppressed basal mRNA levels of the CETP gene in HepG2 cells in a dose-dependent manner. Using gel shift and chromatin immunoprecipitation (ChIP) assays, we found that $FXR{\alpha}$ could bind to the liver X receptor ${\alpha}$ ( $LXR{\alpha}$; NR1H3) binding site (LXRE; DR4RE) located within the CETP 5' promoter region. $FXR{\alpha}$ suppressed $LXR{\alpha}$-induced DR4RE-luciferase activity and this effect was mediated by a binding competition between $FXR{\alpha}$ and $LXR{\alpha}$ for DR4RE. Furthermore, the addition of CDCA together with a $LXR{\alpha}$ ligand, GW3965, to HepG2 cells was shown to substantially decrease mRNA levels of hepatic CETP gene, which is typically induced by GW3965. Together, our data demonstrate that $FXR{\alpha}$ down-regulates CETP gene expression via binding to the DR4RE sequence within the CETP 5' promoter and this $FXR{\alpha}$ binding is essential for $FXR{\alpha}$ inhibition of $LXR{\alpha}$-induced CETP expression.

• BMB Reports
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• 제42권9호
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• pp.605-610
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• 2009

Plasma high-density lipoprotein cholesterol (HDL-C) levels are inversely correlated with the risk of cardiovascular disease, and are known to increase with repetitive exercise. In the current study, HDL fractions from athletes' sera were isolated and compared as a function of the type of sport (runners [n = 10], throwers [n = 10], wrestlers [n = 10], and weight lifters [n = 8]), and as an age- and gender-matched reference group (n = 14). Among athletes, HDL from runners had the strongest antioxidant activity. Immunodetection showed that runners and wrestlers had the highest levels of apoA-I and lowest levels of apoA-II in their HDL. Electron microscopy also revealed that HDL2 of runners and wrestlers were the largest in size. In conclusion, although all athlete groups had significantly better serum lipid/lipoprotein profiles than the reference group, runners and wrestlers had the most desirable lipoprotein function and structure, including antioxidant activity, HDL-associated enzyme activities and increased particle size.

• Molecules and Cells
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• 제27권3호
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• pp.291-297
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• 2009

Apolipoprotein (apo) C-III is a marker protein of triacylglycerol (TG)-rich lipoproteins and high-density lipoproteins (HDL), and has been proposed as a risk factor of coronary heart disease. To compare the physiologic role of reconstituted HDL (rHDL) with or without apoC-III, we synthesized rHDL with molar ratios of apoA-I:apoC-III of 1:0, 1:0.5, 1:1, and 1:2. Increasing the apoC-III content in rHDL produced smaller rHDL particles with a lower number of apoA-I molecules. Furthermore, increasing the molar ratio of apoC-III in rHDL enhanced the surfactant-like properties and the ability to lyse dimyristoyl phosphatidylcholine. Furthermore, rHDL containing apoC-III was found to be more resistant to particle rearrangement in the presence of low-density lipoprotein (LDL) than rHDL that contained apoA-I alone. In addition, the lecithin:cholesterol acyltransferase (LCAT) activation ability was reduced as the apoC-III content of the rHDL increased; however, the CE transfer ability was not decreased by the increase of apoC-III. Finally, rHDL containing apoC-III aggravated the production of MDA in cell culture media, which led to increased cellular uptake of LDL. Thus, the addition of apoC-III to rHDL induced changes in the structural and functional properties of the rHDL, especially in particle size and rearrangement and LCAT activation. These alterations may lead to beneficial functions of HDL, which is involved in anti-atherogenic properties in the circulation.

• Preventive Nutrition and Food Science
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• 제2권2호
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• pp.121-128
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• 1997

this study was conducted to examine the atherogenic effect of high cholesterol diet (experimental diet) that influences changes of lipoprotein cholesterol metabolism and arterial wall. Seven NewZealand white rabbits were fed control diet, an the other 7 rabbits 2% cholesterol diet for 10 weeks. Results obtained from this study are as follows: 1) High cholesterol diet resulted in a gradual increase of plasma total cholesterol level, reaching upto 1422 mg/dl at the seventh week. 2) CETP (cholesteryl ester transfer protein) activity was significantly higher in high cholesterol group (64.9% at the 7th week) than control group (49.3% at the 7th week) during most of the experimental period except the 6th week. 3) The cholesterol supplementation induced fatty liver and a decrease of hepatic HMG-CoA reductase activities (2.1 moles vs. 0.3nmoles) compared to control group. 4) Bands of apo B-100 and apo E in plasma lipoprotein were thicker in high cholesterol-fed animals tan control animals as visualized by SDS-PAGE. 5) Oxidizability of plasma lipoproteins measured in vitro was greater in high cholesterol group tan control group, but vitamin E level higher in control group. 6) he effect of cholesterol feeding for 10 weeks also led to early fatty streaks in aortic intima. High cholesterol feeding was atherogenic to rabbits, an this seems to be mediated through elevated CETP activities that regulate plasma HDL cholesterol level and decrease an efficiency of reverse cholesterol transport in lipoprotein cholesterol metabolism. The enhanced oxidizability of plasma lipoproteins and lowered vitamin E level may also contribute to the formation of faaty streaks in aorta of cholesterol-fed rabbits.

• Nutrition Research and Practice
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• 제17권6호
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• pp.1099-1112
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• 2023

BACKGROUND/OBJECTIVES: Dyslipidemia causes metabolic disorders such as atherosclerosis and fatty liver syndrome due to abnormally high blood lipids. Purple perilla frutescens extract (PPE) possesses various bioactive compounds such as α-asarone, chlorogenic acid and rosmarinic acid. This study examined whether PPE and α-asarone improved dyslipidemia-associated inflammation and inhibited atheroma formation in apolipoprotein E (apoE)-deficient mice, an experimental animal model of atherosclerosis. MATERIALS/METHODS: ApoE-deficient mice were fed on high cholesterol-diet (Paigen's diet) and orally administrated with 10-20 mg/kg PPE and α-asarone for 10 wk. RESULTS: The Paigen's diet reduced body weight gain in apoE-deficient mice, which was not restored by PPE or α-asarone. PPE or α-asarone improved the plasma lipid profiles in Paigen's diet-fed apoE-deficient mice, and despite a small increase in high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein (LDL)-cholesterol, and very LDL were significantly reduced. Paigen's diet-induced systemic inflammation was reduced in PPE or α-asarone-treated apoE-deficient mice. Supplying PPE or α-asarone to mice lacking apoE suppressed aorta atherogenesis induced by atherogenic diet. PPE or α-asarone diminished aorta accumulation of CD68- and/or F4/80-positive macrophages induced by atherogenic diet in apoE-deficient mice. Treatment of apoE-deficient mice with PPE and α-asarone resulted in a significant decrease in plasma cholesteryl ester transfer protein level and an increase in lecithin:cholesterol acyltransferase reduced by supply of Paigen's diet. Supplementation of PPE and α-asarone enhanced the transcription of hepatic apoA1 and SR-B1 reduced by Paigen's diet in apoE-deficient mice. CONCLUSIONS: α-Asarone in PPE inhibited inflammation-associated atheroma formation and promoted hepatic HDL-C trafficking in dyslipidemic mice.

• 한국식품영양과학회지
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• 제42권2호
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• pp.175-181
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• 2013

표고버섯, 표고버섯균사체배양쌀 추출물의 항당뇨와 항비만 효과를 규명하고자 본 연구에서는 표고버섯 80% ethanol 추출물(LE), 표고버섯균사체배양쌀 80% ethanol 추출물(LEM)에서 3T3-L1 preadipocyte cell line을 이용하여 세포의 분화에 미치는 영향을 확인할 수 있었다. 분화유도후 8일 째에 Oil Red O 염색을 통해 세포내 형성된 지방구(lipid droplet)를 isopropanol에 용출하여 500 nm에서 흡광도를 측정한 결과, LE 100 ${\mu}g/mL$에서 p<0.05 수준에서 유의한 억제 효과가 나타났으며, LE 300 ${\mu}g/mL$에서는 p<0.01 수준에서 유의한 억제 효과가 나타났다. LEM은 대조군에 비하여 LEM을 10 ${\mu}g/mL$에서 p<0.05 수준에서 유의한 억제 효과가 나타났으며, LEM 30, 100, 300 ${\mu}g/mL$에서는 p<0.01 수준에서 유의한 억제 효과가 나타났다. CETP 저해 활성을 측정한 결과 LE 300 ${\mu}g/mL$에서 p<0.01 수준에서 유의한 저해효과가 나타났다. LEM을 농도별로 처리하였을 때 대조군에 비하여 농도 의존적으로 억제 효과가 있었으며, LEM 30 ${\mu}g/mL$에서 p<0.05 수준에서 유의한 저해효과가 나타났고 LEM 100, 300 ${\mu}g/mL$에서는 p<0.01 수준에서 유의한 저해효과가 나타났다. PTP1B 저해 활성을 측정한 결과, LE는 대조군에 비하여 LE 10, 30, 100, 1,000 ${\mu}g/mL$에서 통계적으로 p<0.05 수준에서의 유의한 저해효과가 나타났으며, LEM은 대조군에 비하여 농도 의존적으로 통계적으로 p<0.01 수준에서의 유의한 저해효과가 나타났다. 또한 고지방식이에 LE, LEM을 28일간 경구투여 하였을 때 흰쥐의 혈청 총콜레스테롤은 HFD군에 비해 LE군, LEM군에서 모두 유의적인 감소를 나타내었고(p<0.05), 혈청의 중성지방(triglyceride) 농도는 HFD군에 비해 LE, LEM군 모두 감소하는 경향을 나타내었으며 특히 LEM군은 통계적으로 p<0.05 수준에서 유의적인 감소를 나타내었다. 혈청의 HDL-cholesterol은 HFD군과 시료처리군에서 유의적인 차이는 나타나지 않았으며, LDL-cholesterol은 HFD군에 비해 LEM군에서 유의적인 감소를 나타내었다(p<0.01). 이상의 결과로 보아 표고버섯과 표고버섯균사체배양쌀은 지방세포의 분화를 억제시키며, 혈중 지질 조성을 개선시키는 효과가 있음을 알 수 있다.