• Molecules and Cells
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• 제44권2호
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• pp.116-125
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• 2021

Cardiovascular diseases (CVDs) are the most common cause of death in patients with nonalcoholic fatty liver disease (NAFLD) and dyslipidemia is considered at least partially responsible for the increased CVD risk in NAFLD patients. The aim of the present study is to understand how hepatic de novo lipogenesis influences hepatic cholesterol content as well as its effects on the plasma lipid levels. Hepatic lipogenesis was induced in mice by feeding a fat-free/high-sucrose (FF/HS) diet and the metabolic pathways associated with cholesterol were then analyzed. Both liver triglyceride and cholesterol contents were significantly increased in mice fed an FF/HS diet. Activation of fatty acid synthesis driven by the activation of sterol regulatory element binding protein (SREBP)-1c resulted in the increased liver triglycerides. The augmented cholesterol content in the liver could not be explained by an increased cholesterol synthesis, which was decreased by the FF/HS diet. HMG-CoA reductase protein level was decreased in mice fed an FF/HS diet. We found that the liver retained more cholesterol through a reduced excretion of bile acids, a reduced fecal cholesterol excretion, and an increased cholesterol uptake from plasma lipoproteins. Very low-density lipoproteintriglyceride and -cholesterol secretion were increased in mice fed an FF/HS diet, which led to hypertriglyceridemia and hypercholesterolemia in Ldlr-/- mice, a model that exhibits a more human like lipoprotein profile. These findings suggest that dietary cholesterol intake and cholesterol synthesis rates cannot only explain the hypercholesterolemia associated with NAFLD, and that the control of fatty acid synthesis should be considered for the management of dyslipidemia.

• Asian-Australasian Journal of Animal Sciences
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• 제22권6호
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• pp.865-870
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• 2009

In this study, we have attempted to understand the effects of taurine on serum and liver concentrations of cholesterol and triglycerides in broiler chickens and mice in the post-absorptive state, and on in vitro protein synthesis in the livers of broiler chickens and laying hens, as well as the effects of taurine on in vivo protein synthesis in the liver of mice. The experimental animals were subjected to 24 h of starvation in order to perpetuate a post-absorptive state. Serum concentrations of high density lipoprotein cholesterol and triglycerides were significantly (p<0.05) higher in the taurine groups than in the controls in both the broilers and the mice. However, taurine resulted in a significant (p<0.05) reduction in liver concentrations of total cholesterol and triglycerides, relative to what was seen in the control groups of both animals. Taurine stimulated the in vitro synthesis of 57-kDa, 40-kDa and 23-kDa proteins in the liver of broilers, but inhibited the in vitro synthesis of 54-kDa, 37-kDa and 24-kDa proteins. Taurine in the liver of laying hens exerted effects on in vitro protein synthesis, with the exception of the 26-kDa protein which was not detected in broiler liver, but was inhibited by taurine in the liver of laying hens. Unlike the findings regarding in vitro protein synthesis in the liver of broilers or laying hens, taurine appeared to stimulate the synthesis of only two proteins, a 47-kDa and a 40-kDa protein, in the liver of mice. Overall, theses findings indicate that taurine treatment results in a reduction in cholesterol and triglyceride concentrations, and also affects protein synthesis in the livers of broilers, laying hens, and mice.

• 한국식품영양과학회지
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• 제21권5호
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• pp.580-593
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• 1992

Cholesterol have many essential functions as a component of cellular and subcellular membranes, metabolic precursor of bile acids and steroid hormones, and obligatory part of the metabolic systems involved in DNA synthesis and cell division. These essential funtions demand a continuous and appropriate supply of cholesterol to the tissues. Body cholesterol pool is maintained by the balance of acquirement from diets, de novo synthesis, and excretion either as bile acids or neutral steroids. In these metabolic process, cholesterol biosynthesis is controlled by the change in the activity of 3-hydroxy-3methylglutaryl coenzyme A (HMG-CoA) reductase. Under most physiological or nutritional situations, the activity of this enzyme is adroitly regulated to maintain tissue cholesterol balance. Excess cholesterol accumulation in the cells induces the decrease in the number of LDL-receptor, followed by the increase in the level of serum LDL-cholesterol. Increase in the level of serum cholesterol appears to be an important determinant for the incidence of the coronary heart disease. Dietary intervention may be helpful in alleviating an increase in the level of serum cholesterol or body cholesterol pool.

• 한국식품과학회지
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• 제51권3호
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• pp.272-277
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• 2019

본 연구진은 선행연구에서 MCE-DAG를 섭취한 마우스에서 혈중 총 콜레스테롤과 LDL 콜레스테롤의 감소를 보고한 바 있어, 본 연구에서 in vitro를 통해 MCE-DAG와 간의 콜레스테롤 항상성 기전의 관련성을 구명하고자 하였다. LDLR과 같은 콜레스테롤 흡수 관련 인자의 발현이 MCE-DAG에 의해 증가한 반면, LDLR을 억제하는 PCSK9의 발현은 감소하였다. 또한, 콜레스테롤 합성 관련 인자인 HMGCR의 발현이 MCE-DAG에 의해 증가하였고, 전사조절인자인 SREBP2의 발현이 증가하였다. 이러한 결과들은 콜레스테롤의 합성과 흡수가 동시에 증가하였음을 뒷받침한다. 즉, 간 내 콜레스테롤 필요량이 증가함에 따라, 간의 콜레스테롤 합성 및 흡수를 활성화시켜 콜레스테롤 항상성을 유지하는 기전이 촉진되었음을 의미한다. 하지만 간 세포 내 총 콜레스테롤 양은 MCE-DAG에서 영향을 받지 않았다. 콜레스테롤 흡수 및 합성 기전이 촉진되었음에도 세포 내 콜레스테롤 농도가 증가하지 않은 현상은 담즙산 등 콜레스테롤 분비 촉진에 의한 것일 수 있다. 이러한 추론은 추후 콜레스테롤 분비 기전을 검증할 수 있는 실험을 설계하여 검증해볼 필요성이 있다. 결론적으로 MCE-DAG는 세포 내 콜레스테롤 흡수 작용을 촉진하는 효과가 있어 추후 기능성 유지로 활용 가능할 것으로 판단된다.

• Molecules and Cells
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• 제23권1호
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• pp.57-63
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• 2007

Leukotrienes (LTs) are produced by several biosynthetic enzymes including cytosolic phospholipase $A_2$ ($cPLA_2$), 5-lipoxygenase (5-LO), and 5-lipoxygenase activating protein (FLAP) in the perinuclear area. In the present study, we showed that pretreatment with methyl-${\beta}$-cyclodextrin (MβCD), a cholesterol-depleting agent, dramatically reduced the synthesis of LTs in response to A23187 in mast cells. A23187-induced LT synthesis was inhibited by pretreatment with M${\beta}$CD, and this effect was reversed when cholesterol was added. In an approach to identifying the $M{\beta}CD$-sensitive protein(s), we observed that FLAP co-localized with flotillin-1, a lipid raft marker protein, in the lipid raft-rich low-density region of sucrose gradients. In addition, electron microscopic analysis revealed that FLAP co-localized with flotillin-1. Together, these results suggest that FLAP is present in cholesterol-rich lipid raft-like domains and that its localization in these domains is critical for LT synthesis.

• Nutrition Research and Practice
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• 제8권6호
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• pp.632-637
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• 2014

BACKGROUND/OBJECTIVES: The purpose of the current study was to investigate the effect of red pericarp glutinous rice rich in polyphenols (Jakwangchalbyeo, red rice) on serum and hepatic levels of cholesterol and hepatic protein expression linked to synthesis and degradation of cholesterol in a hypercholesterolemic mice diet as compared with brown rice. MATERIALS/METHODS: C57BL/6 male mice were randomly divided into four groups (n = 5 each), which were fed different diets for a period of 12 weeks: American Institute of Nutrition (AIN)-93G diet, AIN-93G diet with 2% cholesterol, brown rice with 2% cholesterol, or red rice with 2% cholesterol. RESULT: Consumption of red rice resulted in a significant decrease in serum level of low-density lipoprotein cholesterol and hepatic levels of triglyceride and total-cholesterol. Expression of acyl-coenzyme A cholesterol acyltransferase-2 (ACAT-2), sterol regulatory element binding protein-2 (SREBP-2), and 3-hydroxyl-3-methylglutaryl coenzyme A (HMG-CoA) reductase was decreased, while expression of phosphorylated adenosine monophosphate activated protein kinase (p-AMPK)/AMPK ratio, cholesterol 7-${\alpha}$-hydroxylase (CYP7a1), and sterol 12-${\alpha}$-hydroxylase (CYP8b1) was increased in mice fed red rice. Brown rice had similar effects on cholesterol metabolism, but the effect of red rice was significantly greater than that of brown rice. CONCLUSIONS: The current study suggested that red rice had a hypocholesterolemic effect by lowering hepatic cholesterol synthesis through ACAT-2, HMG-CoA reductase, and SREBP-2, and by enhancing hepatic cholesterol degradation through CYP7a1 and CYP8b1 in mice fed a hypercholesterolemic diet.

• 한국식품영양과학회지
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• 제44권12호
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• pp.1779-1784
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• 2015

본 연구에서는 마늘의 다양한 조리법에 따른 냉수추출 마늘 추출물이 HepG2 세포 내 콜레스테롤 합성에 미치는 효과에 대하여 알아보고자 세포 내 중성지방 및 콜레스테롤 함량을 확인하고 real-time PCR을 이용하여 작용 기전을 알아보았다. 마늘을 $25^{\circ}C$에서 60분간 숙성하였을 경우 1분간 숙성하였을 때와 비교하여 추출물 내 alliin 함량이 감소하는 것을 확인할 수 있었다. 마늘 추출물을 HepG2 세포에 처리하였을 때 세포 내 중성지방 및 콜레스테롤의 함량이 감소하는 모습을 보여주었으며, 특히 동결건조 마늘 추출물이 그 효과가 가장 우수하였다. 콜레스테롤 합성의 제한효소인 HMGCoA reductase의 발현량 역시 마늘 추출물을 처리함에 따라 감소하는 모습을 보였으며, 동결건조 마늘 추출물을 처리하였을 때 가장 많이 감소하는 모습을 보였다. 다만 산성처리를 한 마늘의 추출물을 세포에 처리하였을 때에는 그 효과가 감소하는 것으로 나타났다. 동결건조 마늘 추출물의 농도 비례 효과를 살펴본 결과 동결건조 마늘 추출물의 경우 생마늘을 상온에 60분 숙성시킨 마늘 추출물과 구운마늘 추출물에 비하여 세포 내 중성지방과 콜레스테롤 합성 감소에 효과가 뛰어난 것으로 나타났으며, 이러한 결과는 HMGCoA reducatase mRNA의 상대적 발현 수준 차이 이상의 지질 감소 효과를 나타내는 것을 확인할 수 있었다. 따라서 동결건조 마늘의 경우 생마늘을 섭취하였을 때와 유사한 또는 더 우수한 효능을 보이면서도 오히려 보관성이 우수하고 생마늘 섭취 시 나타날 수 있는 과민 반응 및 알레르기 반응의 위험이 적기 때문에 다양하게 응용될 수 있는 가능성이 있을 것으로 사료되며, 이를 뒷받침할 방안들의 연구가 진행되어져야 할 것으로 판단된다.

• Preventive Nutrition and Food Science
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• 제4권2호
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• pp.125-129
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• 1999

The influence of dietary cholesterol on phospolipid metabolism in rat liver microsmes was studied in rats fed a diet containing fish oil(FO) or beef tallow (BT). The hepatic phospholipid content decreased wherease gepatic triglyceride and cholesterol increased significantly in both groups after cholestered supplementation. Plasma concentrations of phospholipid and traiglyceride increased with cholesterol supplement in both groups while cholesterol decreased only moderately in the FO group. Dietary cholesterol affected microsomal phosphiolpids in liver ; the proportation of phosphatidylcholine decreased in the FO group, an d it also slightly decreased in the BT group at the expense of phosphatidylethanolamine. The activity of CTP : phospocholine cytidylytransferase , the rate-limiting enzyme of phosphatidylcholine synthesis, increased inhepatic mocrosomes whreas it decreased in hepatic cytosol of both groups by cholesterol supplementation. In conclusion, these indicated that the dietary cholesterol profoundly influences phospholipid metabolism in the rat liver.

• Nutrition Research and Practice
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• 제15권4호
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• pp.431-443
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• 2021

BACKGROUND/OBJECTIVES: Nobiletin (NOB), a citrus flavonoid, is reported to have beneficial effects on cardiovascular and metabolic health. However, there is limited research investigating the effect of long-term supplementation with low-dose NOB on high-cholesterol diet (HCD)-induced hypercholesterolemia and non-obese nonalcoholic fatty liver disease (NAFLD). Therefore, we investigated the influence of NOB on hypercholesterolemia and NAFLD in HCD-fed mice. SUBJECTS/METHODS: C57BL/6J mice were fed a normal diet (ND) or HCD (35 kcal% fat, 1.25% cholesterol, 0.5% cholic acid) with or without NOB (0.02%) for 20 weeks. RESULTS: HCD feeding markedly reduced the final body weight compared to ND feeding, with no apparent energy intake differences. NOB supplementation suppressed HCD-induced weight loss without altering energy intake. Moreover, NOB significantly decreased the total cholesterol (TC) levels and the low-density lipoprotein (LDL)/very-LDL-cholesterol to TC ratio, and increased the high-density lipoprotein-cholesterol/TC ratio in plasma, compared to those for HCD feeding alone. The plasma levels of inflammatory and atherosclerosis markers (C-reactive protein, oxidized LDL, interleukin [IL]-1β, IL-6, and plasminogen activator inhibitor-1) were significantly lower, whereas those of anti-atherogenic adiponectin and paraoxonase were higher in the NOB-supplemented group than in the HCD control group. Furthermore, NOB significantly decreased liver weight, hepatic cholesterol and triglyceride contents, and lipid droplet accumulation by inhibiting messenger RNA expression of hepatic genes and activity levels of cholesterol synthesis-, esterification-, and fatty acid synthesis-associated enzymes, concomitantly enhancing fatty acid oxidation-related gene expression and enzyme activities. Dietary NOB supplementation may protect against hypercholesterolemia and NAFLD via regulation of hepatic lipid metabolism in HCD-fed mice; these effects are associated with the amelioration of inflammation and reductions in the levels of atherosclerosis-associated cardiovascular markers. CONCLUSIONS: The present study suggests that NOB may serve as a potential therapeutic agent for the treatment of HCD-induced hypercholesterolemia and NAFLD.

• Journal of Microbiology and Biotechnology
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• 제11권4호
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• pp.712-715
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• 2001

A new combined method including the enzymatic hydrolysis of $\beta$-cyclodextrin ($\beta$-CD) and solvent extraction fo cholesterol from the hydrolyzed mixture was developed to recover cholesterol from a $\beta$-CD-cholesterol complex prepared from dairy products, such as cream, milk, and cheese. Cyclomaltodextrinase (cyclomatodextrin dextrin hydrolase, EC 3.2.1.54, DCase_ prepared form alkalophilic Bacillus sp. KJ 133 hydrolyzed the $\beta$-DC of the $\beta$-CD-cholesterol complex, and then, free cholesterol was efficiently extracted from the hydrolyzed mixture by a nonpolar solvent such as ethyl acetate. To increase the stability of free CDase, immobilized CDase was developed using sodium alginate as a carrier. The immobilized CDase showed a high recovery yield of cholesterol in a time-dependent manner compared to the free CDase. A gas chromatography analysis showed that more than 70% of cholesterol was recovered from the $\beta$-DC-cholesterol complex of cream by the immobilized CDase, whereas only 3% and 29% of cholesterol were recovered when the solvent extraction and free CDase treatment were used, respectively. The cholesterol recovered can be used as a raw material for steroid synthesis. Furthermore, this method can be an efficient way to recover cholesterol or other organic compounds that are bound in a $\beta$ -DC-cholesterol or -organic compound complex.