組織中 Triacylglycerides의 酵素學的 定量

李鎭基,李仁善,鄭泰浩 慶北大學校 醫科大學 1986 慶北醫大誌 Vol.27 No.3

조직중 triglycerides의 정량은 지금까지 보고된 방법들이 어렵다는 이유로 총 지질과 phospholidpis, cholesterol을 측정한 후 총지질에서 phospholipids와 cholesterol을 뺀것을 triglycerides의 함량으로 사용하고 있는 실정이다. 본 연구는 조직중 triglycerides를 효소법으로 측정하는 방법을 고안하여 그 평가와 함께 소개하였다. 조직에서 지질을 Folch등의 방법으로 추출한 후 chloroform층을 취하여 증발건조 시켰다. 건조된 지질 추출물에 소량의 isopropanol을 가하여 완전히 녹인 후 여기에 효소시약을 가하여 triglycerides를 측정하였다. Isopropanol은 유기용매이면서도 소량을 사용할 시에는 효소의 활성도에 영향을 미치지 않았다. 본 효소법의 재현성과 검사신뢰도는 우수하였다. 또한 본 효소법을 간장, 피지선등의 조직에 적용하여 좋은 결과를 얻었으며 지질을 유기용매로 추출해야만 하는 상황에도 적용하여 triglycerides를 쉽게 정량할 수 있었다. In this method for rapid enzymatic determination of triglycerides, the lipid extracts from tissue are dissolved in small amount of isopropanol, and are reacted directly with the equous enzymatic reagent, without further procedures. The presence of isopropanol does not interfere with enzymatic activity. The method is reproducible, and offers advantages of simplicity over previous methods. This method also can be used for measuring triglycerides in lipid extracts from various tissues and hemolyzed serum.

Determination of Carnitine Renal Threshold and Effect of Medium-Chain Triglycerides on Carnitine Profiles in Newborn Pigs

Heo, K.N.,Odle, J.,Lin, X.,van Kempen, T.A.T.G.,Han, In K. Asian Australasian Association of Animal Productio 2001 Animal Bioscience Vol.14 No.2

Colostrum deprived, newborn pigs (N=12, $1.64{\pm}0.05kg$) were used to study the renal threshold of carnitine, and effects of emulsified medium-chain triglyceride (MCT, tri-8:0) feeding on kinetics of plasma carnitine and urinary carnitine excretion. An arterial catheter was inserted through an umbilical artery, and a bladder catheter was inserted via the urachus. Piglets were oro-gastrically gavaged with one of six carnitine levels (0, 60, 120, 180, 240, $480{\mu}mol/kg\;W^{0.75}$) with (+MCT) or without medium-chain triglycerides (-MCT) in 0.9% NaCl solution. Blood was sampled into heparinized tubes at 0, 1, 2, 4, 6, 8, 14, and 20 h after gavage, and urine was collected and pooled into 1 h or 2 h composite samples to determine free- and short-chain carnitine concentrations. Plasma from the 12 newborn piglets before gavage contained $10.6{\pm}1.2{\mu}mol/L$ free carnitine and $7.2{\pm}0.6{\mu}mol/L$ acid-soluble acyl carnitine. The renal threshold for carnitine was similar between the MCT and the +MCT group (42.6 13.1 and $46.4{\pm}2.0{\mu}mol/L$, respectively), but the correlation between plasma free carnitine and urinary excretion was altered. Plasma free carnitine linearly increased with increasing carnitine dosage (-MCT group, $R^2=0.95$, p<0.001; +MCT group, $R^2=0.91$, p<0.001), but was decreased by 50% when medium-chain triglycerides were fed. The peak in plasma free carnitine concentration was depressed by medium-chain triglycerides feeding also. Therefore, the plasma and urinary short-chain/free carnitine ratio of the +MCT group was increased by 100% and 40%, respectively (p<0.01). Feeding of medium-chain triglycerides may delay plasma carnitine elevation via altering the kinetics of absorption. Similarly, the plasma and urinary short-chain/free carnitine ratio were affected by interaction between medium-chain triglycerides and time (p<0.01). The present study suggests that an oral carnitine dose over $480{\mu}mol/kg\;W^{0.75}$ may be needed to reach the free carnitine renal threshold within a short period, especially when provided together with medium-chain triglyceride.

Berberine and Dyslipidemia: Different Applications and Biopharmaceutical Formulations Without Statin-Like Molecules—A Meta-Analysis

Alexander Bertuccioli,Sara Moricoli,Stefano Amatori,Marco Bruno Luigi Rocchi,Giorgia Vici,Davide Sisti 한국식품영양과학회 2020 Journal of medicinal food Vol.23 No.2

The aim of this study was to analyze the efficacy of berberine taken alone or in other formulations (with silymarin or other mixtures) on dyslipidemia through a systematic review of the literature and a meta-analysis. A systematic investigation was conducted on 19 studies that were selected based on inclusion and exclusion criteria. Both controlled trials (n = 12) and cross-sectional trials (n = 7) were included. The following formulations were examined: berberine used alone (n = 5), berberine combined with silymarin (n = 8), and other mixture containing berberine (n = 6). A meta-analysis was performed using a fixed-effects model and meta-regression. Total cholesterol (TC), low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol, and triglycerides were considered. Moreover, possible associations of each parameter with age and the dose and duration of the treatment were analyzed. The data obtained showed a significant reduction in TC and LDL cholesterol for each formulation. A reduction in triglycerides was also observed for both TC and LDL but with a smaller impact. As regards HDL, a slight increase was observed, but it was not statistically significant. The formulation of berberine in association with silymarin was found to have the greatest impact on TC, LDL, HDL, and triglycerides. The greater efficacy of the formulation consisting of berberine associated with silymarin can probably be accounted for by the fact that the latter increases the bioavailability of berberine. However, it is necessary to carry out further clinical studies to better define the efficacy of the treatment and which patients show the best response.

고콜레스테롤혈증 치료에서 심바스타틴 10mg 과 20mg 사용시의 효능 및 안전성 비교 연구

이재건(Jae Gun Lee),김화민(Hwa Min Kim),이현희(Hyun Hee Lee),최혜진(Hae Jin Choi),박창하(Chang Ha Park),서명덕(Myung Deok Seo),정재천(Jae Cheon Jeong),조한균(Han Kyun Cho),최성식(Sung Sik Choi),이지현(Ji Hyun Lee),김석연(Seok Yeon Ki 대한내과학회 2002 대한내과학회지 Vol.63 No.1

목적 : 지방공사 강남병원 순환기 내과에서 추적 검사 받는 고지혈증 환자 106명을 대상으로, 심바스타틴 상용량인 10 mg과 20 mg 사용시의 콜레스테롤 저하 효과, 부작용 등에 대해 조사하였다. 방법 : NCEP guideline에 따라 약물 치료가 필요한 환자 중 저비중 지단백 콜레스테롤 농도가 130 mg/dL 이상이면서 중성 지방 농도는 400 mg/dL 이하인 고콜레스테롤혈증 환자를 대상으로 심바스타틴 사용량을 10 mg 군과 20 mg 군으로 무작위적으로 나누어 처방한 후 6개월 후의 혈중 지질 농도를 분석하였다. 환자들은 매월 부작용 여부를 확인하기 위해 정기적 외래 검진을 받았으며 심각한 부작용이 나타나거나 합병증이 나타난 경우 치료 대상에서 제외하였다. 1997년 4월부터 2000년 11월까지의 115명 중 탈락되지 않은 106명의 결과를 분석하였다. 결과: 남녀비는 40:66이었고, 전체 대상군 중 55%에서 고혈압이 있었고, 9%에서 관상동맥 질환이 있었으며, 13%에서 당뇨병이 존재하였다. 심바스타틴 투여 전 평균 지질 농도는 258-201-50-167 (총 콜레스테롤-TG- HDL-LDL)이었다. 저비중 지단백 콜레스테롤 농도는 20 mg 군에서 34.9 mg/dL, 10 mg 군에서는 20.8 mg/dL 감소하였고, 20 mg 군이 10 mg 군에 비해 저비중 지단백 콜레스테롤 농도를 의미 있게 더 감소시켰다. 총 콜레스테롤 농도는 20 mg 군에서 22.7 mg/dL, 10 mg 군에서 21.7 mg/dL 감소하였고, 심바스타틴 복용 용량에 따른 감소 효과의 차이는 없었다. 심바스타틴 용량에 따른 NCEP guideline (ATP III)의 저비중 지단백 콜레스테롤 목표 농도 달성 정도를 조사한 결과 관상동맥 질환의 위험 인자가 0∼1개인 저위험군에서는 20 mg 군이 80%, 10 mg 군이 81%에서 목표 농도가 되었고, 고위험군에서는 20 mg 군 50%, 10 mg 군 35%가 목표 농도에 도달하여 저위험군에 비해 치료 성공률이 낮았다. 중성 지방 농도는 10 mg 군과 20 mg 군 모두에서 의미있게 감소하지 않았으나 200 mg/dL 이상의 고중성지방군에서는 심바스타틴 20 mg 사용 군에서 22.3 mg/dL, 10 mg 군에서 42.7 mg/dL 감소하여 10 mg 사용 군에서 20 mg 사용 군에 비해 의미 있게 중성 지방을 감소시켰다. 고비중 지단백 콜레스테롤은 심바스타틴 복용 전 농도가 40 mg/dL 미만인 경우에는 20 mg 복용 군에서 11.5 mg/dL, 10 mg 복용 군에서 8.3 mg/dL가 증가하였다. 6개월간의 심바스타틴 치료를 하는 동안에 부작용 때문에 약물 복용을 중단한 경우는 전신 근육통이 심해 중단한 것 외에는 없었고, 심각한 부작용을 가진 환자는 없었다. 연구 대상 환자들에 대한 약물 용량에 대한 선호도 조사 결과 10 mg에 대한 선호도가 높았다. 결론: 심바스타틴은 고콜레스테롤혈증 한국인에서 10 mg과 20 mg 사용시 모두 지질 농도를 개선하는데 효과적이었다. 그러나 관상동맥성 심질환을 가진 고위험군에서는 NCEP guideline을 만족시키는데 효과적이지 못했다. 환자들의 선호도를 고려할 때 고위험군외에는 초기 치료 용량을 10 mg으로 시작하는 것이 좋을 것으로 보인다. Background: Elevated serum cholesterol level is a major risk factor for cardiovascular morbidity and mortality. Simvastatin is effective for treating hypercholesterolemia. The aim of the study was to evaluate efficacy and safety of 6-month therapy with simvastatin with relatively low dose, 10 mg and 20 mg/day. Methods: One hundred six patients with hyperlipidemia (triglycerides<400 mg/dL and low- density lipoprotein (LDL) cholesterol>130 mg/dL) were randomized to receive either simvastatin 10 mg/day (n=43) or 20 mg/day (n=63). Efficacy was determined by measuring changes from baseline in lipid parameters including LDL cholesterol, total cholesterol, triglycerides and high-density lipoprotein (HDL) cholesterol. Results: Of the one hundred six patients randomized to treatment, forty patients were men and sixty-six patients were women. Fifty-five percent of patients had hypertension, nine percent coronary artery disease and thirteen percent type 2 diabetes mellitus. Mean baseline lipid concentrations were 258 (total cholesterol), 201 (triglycerides), 50 (HDL) and 167 mg/dL (LDL). Both 10 mg and 20 mg of simvastatin produced statistically significant improvements in all measured serum lipid parameters (p<0.001). Compared with 10 mg of simvastatin, 20 mg of simvastatin produced significantly greater (p<0.001) reductions from baseline LDL cholesterol (34.9 mg/dL vs 20.8 mg/dL). But 10 mg of simvastatin was more effective than 20 mg of simvastatin at reducing triglycerides level (42.7 mg/dL vs 22.3 mg/dL). There was no significant difference in both doses at improving total cholesterol and HDL cholesterol level. Percentage of patients at goal LDL as recommended by NCEP guideline (ATP III) were 81% and 80% for patients in low risk but 35% and 50% for patients in coronary heart disease and its risk equivalents, taking 10 mg and 20 mg/day respectively. Both doses were well tolerated. Only 3 patients (4.8%) in the 20 mg group and one patient (2.3%) in the 10 mg group experienced mild adverse events. Most patients contacted by telephone wanted to take 10 mg of simvastatin. Conclusion: In patients with hypercholesterolemia in Korea, both doses (10 mg, 20 mg) of simvastatin were effective in improving serum lipid parameters and well-tolerated. We recommend, considering patients' preference, that 10 mg of simvastatin be intial dosage and in patients with coronary heart disease, higher doses than 20 mg should be prescribed to allow most patients to reach their NCEP target levels.(Korean J Med 63:46-53, 2002)

홍삼류의 섭취가 비만과 혈중 지질의 상호관계에 미치는 영향

박화진,이정희,이소진,함혜선,조현정,임창률,유영빈,박기현 대한의생명과학회 2000 Journal of biomedical laboratory sciences Vol.6 No.4

비만은 동맥경화의 위험인자로서 혈중에 triglyceride의 농도를 종가시키고, 상대적으로 HDL-Cholesterol의 농도를 감소시킴과 동시에 수축기 혈압을 상승시킨다. 본 연구에서 홍삼제품류를 4년 또는 5년 동안 복용해 온 건강한 사람 (ginseng군)과 홍삼제품을 복용하지 않은 건강한 사람 (control군)을 대상으로 하여 신체 계측치로부터 비만지수를 구하고 이것과 혈중의 triglyceride (TG)농도, TG/HDL-Cholesterol ratio 및 수축기 혈압과의 상호관계를 연구한 바, ginseng군에서는 대조군에 비해 혈중의 TG 농도가 일정하게 유지되었고, TG/HDL-Cholesterol ratio 및 수축기 혈압도 일정하게 유지되었다. 이러한 현상은 ginseng군에서 기호품으로 alcohol을 섭취하거나, 흡연을 한 경우에도 상관없이 일정하게 유지 되었다. 이 결과는 홍삼제품류를 장기 복용하면 비만의 저하 및 고혈압 또는 동맥경화의 위험인자가 억제될 수 있고, 결론적으로 비만, 고혈압 및 동맥경화를 예방할 수 있을 것으로 추정한다. Obesity is the risk fcactor of atherosclerosis and not only increases triglyceride concentration in blood but also decreases relatively the ratio of TG to HDL-Cholesterol in blood. In case of obesity, systolic blood pressure is also increased in responding the increase of TG in blood. Index of obesity in red ginseng-taking group (ginseng group) was lower as compared with non-red ginseng-taking group (control group). The TG concentration, the ratio of triglyceride to HDL-cholesterol in blood and systolic blood pressure were decreased in the subjects of ginseng group compared with that in control group. It is inferred that long-term intake of ginseng products may help to prevent the risk of atherosclerosis and obesity.

Triglyceride-Glucose Index Predicts Future Atherosclerotic Cardiovascular Diseases: A 16-Year Follow-up in a Prospective, Community-Dwelling Cohort Study

문준호,김용강,오태정,문재훈,곽수헌,박경수,장학철,최성희,조남한 대한내분비학회 2023 Endocrinology and metabolism Vol.38 No.4

Background: While the triglyceride-glucose (TyG) index is a measure of insulin resistance, its association with cardiovascular disease (CVD) has not been well elucidated. We evaluated the TyG index for prediction of CVDs in a prospective large communitybased cohort. Methods: Individuals 40 to 70 years old were prospectively followed for a median 15.6 years. The TyG index was calculated as the Ln [fasting triglycerides (mg/dL)×fasting glucose (mg/dL)/2]. CVDs included any acute myocardial infarction, coronary artery disease or cerebrovascular disease. We used a Cox proportional hazards model to estimate CVD risks according to quartiles of the TyG index and plotted the receiver operating characteristics curve for the incident CVD. Results: Among 8,511 subjects (age 51.9±8.8 years; 47.5% males), 931 (10.9%) had incident CVDs during the follow-up. After adjustment for age, sex, body mass index, diabetes mellitus, hypertension, total cholesterol, smoking, alcohol, exercise, and C-reactive protein, subjects in the highest TyG quartile had 36% increased risk of incident CVD compared with the lowest TyG quartile (hazard ratio, 1.36; 95% confidence interval, 1.10 to 1.68). Carotid plaque, assessed by ultrasonography was more frequent in subjects in the higher quartile of TyG index (P for trend=0.049 in men and P for trend <0.001 in women). The TyG index had a higher predictive power for CVDs than the homeostasis model assessment of insulin resistance (HOMA-IR) (area under the curve, 0.578 for TyG and 0.543 for HOMA-IR). Adding TyG index on diabetes or hypertension alone gave sounder predictability for CVDs. Conclusion: The TyG index is independently associated with future CVDs in 16 years of follow-up in large, prospective Korean cohort.

Triglyceride-Rich Lipoproteins and Novel Targets for Anti-atherosclerotic Therapy

Željko Reiner 대한심장학회 2018 Korean Circulation Journal Vol.48 No.12

Although elevated serum low-density lipoprotein-cholesterol (LDL-C) is without any doubts accepted as an important risk factor for cardiovascular disease (CVD), the role of elevated triglycerides (TGs)-rich lipoproteins as an independent risk factor has until recently been quite controversial. Recent data strongly suggest that elevated TG-rich lipoproteins are an independent risk factor for CVD and that therapeutic targeting of them could possibly provide further benefit in reducing CVD morbidity, events and mortality, apart from LDL-C lowering. Today elevated TGs are treated with lifestyle interventions, and with fibrates which could be combined with omega-3 fatty acids. There are also some new drugs. Volanesorsen, is an antisense oligonucleotid that inhibits the production of the Apo C-III which is crucial in regulating TGs metabolism because it inhibits lipoprotein lipase (LPL) and hepatic lipase activity but also hepatic uptake of TGs-rich particles. Evinacumab is a monoclonal antibody against angiopoietin-like protein 3 (ANGPTL3) and it seems that it can substantially lower elevated TGs levels because ANGPTL3 also regulates TGs metabolism. Pemafibrate is a selective peroxisome proliferator-activated receptor alpha modulator which also decreases TGs, and improves other lipid parameters. It seems that it also has some other possible antiatherogenic effects. Alipogene tiparvovec is a nonreplicating adeno-associated viral vector that delivers copies of the LPL gene to muscle tissue which accelerates the clearance of TG-rich lipoproteins thus decreasing extremely high TGs levels. Pradigastat is a novel diacylglycerol acyltransferase 1 inhibitor which substantially reduces extremely high TGs levels and appears to be promising in treatment of the rare familial chylomicronemia syndrome.

New Therapeutic Approaches to the Treatment of Dyslipidemia 1: ApoC-III and ANGPTL3

김지윤,김남훈 한국지질동맥경화학회 2023 지질·동맥경화학회지 Vol.12 No.1

Low-density lipoprotein cholesterol (LDL-C)-lowering therapy that increases LDL receptor expression in several ways robustly reduces the risk of atherosclerotic cardiovascular disease (CVD). However, a substantial risk of CVD still remains after intensive LDL-C reduction, which requires new treatment modalities for dyslipidemia and cardiovascular risk management. Triglycerides (TGs) and triglyceride-rich lipoproteins (TRLs) have received attention as indicators of residual cardiovascular risk and as direct causal factors for atherosclerosis and CVDs. Advances in understanding TG and TRL metabolism and their association with clinically evident CVDs have led to the development of novel therapeutic targets, including apolipoprotein C-III (apoC-III) and angiopoietin-like protein 3 (ANGPTL3). Genetic association studies have indicated that both apoC-III and ANGPTL3 play a causal role in the development of atherosclerotic CVD. Both molecules contribute to lipid dysregulation and atherosclerosis primarily by inhibiting lipoprotein lipase; however, recent evidence has shown that novel pathways exist in relation to their lipid-modifying activities. Notably, recent progress in therapeutic approaches, such as monoclonal antibodies or antisense oligonucleotides, has led to several novel therapeutics targeting apoC-III and ANGPTL3. This review summarized the recent updates and discussions related to apoC-III and ANGPTL3 expression.

Lipoprotein Lipase: Is It a Magic Target for the Treatment of Hypertriglyceridemia

문준호,김규호,최성희 대한내분비학회 2022 Endocrinology and metabolism Vol.37 No.4

High levels of triglycerides (TG) and triglyceride-rich lipoproteins (TGRLs) confer a residual risk of cardiovascular disease after optimal low-density lipoprotein cholesterol (LDL-C)–lowering therapy. Consensus has been made that LDL-C is a non-arguable primary target for lipid lowering treatment, but the optimization of TGRL for reducing the remnant risk of cardiovascular diseases isurged. Omega-3 fatty acids and fibrates are used to reduce TG levels, but many patients still have high TG and TGRL levels combined with low high-density lipoprotein concentration that need to be ideally treated. Lipoprotein lipase (LPL) is a key regulator forTGs that hydrolyzes TGs to glycerol and free fatty acids in lipoprotein particles for lipid storage and consumption in peripheral organs. A deeper understanding of human genetics has enabled the identification of proteins regulating the LPL activity, which includethe apolipoproteins and angiopoietin-like families. Novel therapeutic approach such as antisense oligonucleotides and monoclonalantibodies that regulate TGs have been developed in recent decades. In this article, we focus on the biology of LPL and its modulators and review recent clinical application, including genetic studies and clinical trials of novel therapeutics. Optimization of LPL activity to lower TG levels could eventually reduce incident atherosclerotic cardiovascular disease in conjunction with successfulLDL-C reduction.

The Relationship between the Triglyceride to High-Density Lipoprotein Cholesterol Ratio and Metabolic Syndrome

신현규,김영광,김용환,정요한,강희철 대한가정의학회 2017 Korean Journal of Family Medicine Vol.38 No.6

Background: Metabolic syndrome is associated with cardiovascular diseases and is characterized by insulin resistance. Recent studies suggest that the triglyceride/high-density lipoprotein cholesterol (TG/HDLC) ratio predictsinsulin resistance better than individual lipid levels, including TG, total cholesterol, low-density lipoprotein cholesterol(LDLC), or HDLC. We aimed to elucidate the relationship between the TG/HDLC ratio and metabolic syndromein the general Korean population. Methods: We evaluated the data of adults ≥20 years old who were enrolled in the Korean National Health and NutritionExamination Survey in 2013 and 2014. Subjects with angina pectoris, myocardial infarction, stroke, or cancerwere excluded. Metabolic syndrome was defined by the harmonized definition. We examined the odds ratios (ORs)of metabolic syndrome according to TG/HDLC ratio quartiles using logistic regression analysis (SAS ver. 9.4; SASInstitute Inc., Cary, NC, USA). Weighted complex sample analysis was also conducted. Results: We found a significant association between the TG/HDLC ratio and metabolic syndrome. The cutoff valueof the TG/HDLC ratio for the fourth quartile was ≥3.52. After adjustment, the OR for metabolic syndrome in thefourth quartile compared with that of the first quartile was 29.65 in men and 20.60 in women (P<0.001). Conclusion: The TG/HDLC ratio is significantly associated with metabolic syndrome.