• Journal of Nutrition and Health
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• 제30권10호
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• pp.1140-1152
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• 1997

Serum and liver lipid levels and fatty acid composition of liver phospolipids (PL) were investigated in 36 rats which consumed either one of five different dietary fats or a high carbohydrate diet for 4 weeks. As the sources of five dietary fats, concentrated cicosapentaenoic acid(EPA), fish oil (FO), perilla oil(PO), corn oil(CO) and beef tallow (BT) were provided to the rats. As a control group, cron starch (CS) replaced dietary fat. The FO group showed lower serum total cholesterol (TC), high density lipiprotein cholesterol(HDL-C) and serum PL levels than those of the CO group(p<0.05). There were no significant differences in serum TC and serum HDL-C levels between the polyunsatured fatty acid(PUFA) groups and the EPA, FO and PO groups. The CS group showed the highest level serum TC. Compared with the CS group, both the EPA and CO groups showed significantly lower atherogenic indices(AI). However, there were no significant differences in AI among different dietary fat groups. No significant differences in liver triglyceride (TG) , TC and PL levels were detected among the six experimental groups. Phosphatidylcholine(PC) and phosphatidylethanolamine(PE) composed 30-40% and 15-20% of total liver PL, respectively. The fatty acid composition of liver PC and PE reflected dietary fatty acid composition . Compared to the different dietary fat based diets used in our study, the high carbohydrate diet had the most adverse effects on serum lipid profiles. However, we can not conclude from this result that long chain n-3 PUFA diets such as the EPA and FO based diets have more beneficial effects on serum lipid profiles than n-6 PUFA diet such as the CO based diet or shorter chain n-3 PUFA diets like the PO based diet.

• BMB Reports
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• 제54권6호
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• pp.323-328
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• 2021

Periodontal diseases have been reported to have a multidirectional association with metabolic disorders. We sought to investigate the correlation between periodontitis and diabetes or fatty liver disease using HFD-fed obese mice inoculated with P. gingivalis. Body weight, alveolar bone loss, serological biochemistry, and glucose level were determined to evaluate the pathophysiology of periodontitis and diabetes. For the evaluation of fatty liver disease, hepatic nonalcoholic steatohepatitis (NASH) was assessed by scoring steatosis, inflammation, hepatocyte ballooning and the crucial signaling pathways involved in liver metabolism were analyzed. The C-reactive protein (CRP) level and NASH score in P. gingivalis-infected obese mice were significantly elevated. Particularly, the extensive lobular inflammation was observed in the liver of obese mice infected with P. gingivalis. Moreover, the expression of metabolic regulatory factors, including peroxisome proliferator-activated receptor γ (Pparγ) and the fatty acid transporter Cd36, was up-regulated in the liver of P. gingivalis-infected obese mice. However, inoculation of P. gingivalis had no significant influence on glucose homeostasis, insulin resistance, and hepatic mTOR/AMPK signaling. In conclusion, our results indicate that P. gingivalis can induce the progression of fatty liver disease in HFD-fed mice through the upregulation of CD36-PPARγ axis.

• Pediatric Gastroenterology, Hepatology & Nutrition
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• 제24권3호
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• pp.295-305
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• 2021

Purpose: Hepcidin levels have previously been reported to be correlated with liver damage. However, the association between hepcidin levels and liver fibrosis in children with fatty liver disease remains unclear. This study therefore aimed to investigate the pathophysiology of fibrosis in children with fatty liver disease and its association with hepcidin levels. Methods: This retrospective case series included 12 boys aged 6-17 years who were diagnosed with nonalcoholic fatty liver disease (NAFLD) or nonalcoholic steatohepatitis (NASH) at the Tokyo Medical University Hospital. Sixteen liver biopsy samples from 12 subjects were analyzed. Serum hepcidin levels were assayed using enzyme-linked immunosorbent assay. Immunostaining for hepcidin was performed, and the samples were stratified by staining intensity. Results: Serum hepcidin levels were higher in pediatric NAFLD/NASH patients than in controls. Conversely, a significant inverse correlation was observed between hepcidin immunostaining and Brunt grade scores and between hepcidin scores and gamma-glutamyltranspeptidase, hyaluronic acid, and leukocyte levels. We observed inverse correlations with a high correlation coefficient of >0.4 between hepcidin immunostaining and aspartate aminotransferase, alanine aminotransferase, total bile acid, and platelet count. Conclusion: There was a significant inverse correlation between hepcidin immunoreactivity and fibrosis in pediatric NAFLD patients; however, serum hepcidin levels were significantly higher, suggesting that these patients experienced a reduction in the hepcidin-producing ability of the liver in response to iron levels, leading to subsequent fibrosis. Therefore, hepcidin levels can be used as markers to identify the progression of fibrosis in patients with NAFLD.

• The Korean Journal of Physiology and Pharmacology
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• 제27권4호
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• pp.299-310
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• 2023

Non-alcoholic fatty liver disease (NAFLD) is a complex disorder characterized by the accumulation of fat in the liver in the absence of excessive alcohol consumption. It is one of the most common liver diseases worldwide, affecting approximately 25% of the global population. It is closely associated with obesity, type 2 diabetes, and metabolic syndrome. Moreover, NAFLD can progress to non-alcoholic steatohepatitis, which can cause liver cirrhosis, liver failure, and hepatocellular carcinoma. Currently, there are no approved drugs for the treatment of NAFLD. Therefore, the development of effective drugs is essential for NAFLD treatment. In this article, we discuss the experimental models and novel therapeutic targets for NAFLD. Additionally, we propose new strategies for the development of drugs for NAFLD.

• Journal of Nutrition and Health
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• 제27권6호
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• pp.537-551
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• 1994

The dietry effects of marine n-3, plant n-3 and plant n-6 fatty acid on serum lipids levels, liver phospholipid fatty acid composition in rat were investigated. Four groups of male Sprague-Dawley rats, 30 weeks old, were fed on one of 4 different experimental diets for 4 weeks. The diets were composed of 15% fat(w/w) of either concentrated EPA oil(20:5, n-3 : 65%), fish oil(20:5, n-3 : 19%, 22:6, n-3 : 18%), perilla oil(18:3, n-3 : 60%) or corn oil(18:2, n-6 : 49%). Blood was initially taken before experimental feeding and also taken after 2 weeks and 4 weeks feeding the diet respectively and then examined for the levels of serum lipids. Rats were sacrificed at 4 weeks after the diet for the analysis of liver phospholipid fatty acid. EPA feeding remarkably decreased the serum levels of triglyceride, total cholesterol, HDL-cholesterol and total phospholipid than any other oil feeding. Fish oil feeding decreased serum HDL-cholesterol level comparable to the effect of EPA feeding and decreased total cholesterol and phospholipid less than but close to the effect of EPA feeding. Perilla oil feeding did not change serum levels of triglyceride and phospholipid, but it decreased serum total cholesterol a lot and HDL-cholesterol a little. Corn oil feeding did not affect triglyceride and total cholesterol while it increased serum level of HDL-cholesterol and total phospholipid. Serum HDL-cholesterol level was increased only in corn oil group. But contrary to the result of serum total phospholipid, liver phospholipid level found to be higher in fish oil and EPA groups than in perilla oil and corn groups. The fatty acid composition of liver phospholipid, phosphatidylcholine(PC) and phosphatidyl ethanolamine(PE) turned out to be affected by dietary fatty acid. 18:2 of liver PC was the lowest in FO group following CO group. The ratio of 20:4/18:2 was lower in PO group than in EPA group in consequence of higher 18:2 and lower 20:4 in PO group and vise versa in EPA group. In the liver PC and PE, similar trends in the ratios of n-6/n-3 and 20:4/18 were found showing higher ratios with CO and EPA group over FO and PO group. EPA group showed the lowest level of 20:5 and lower level of 20:6 than group. Fish oil was more efficient than EPA oil and PO in lowering the ratio of n-6/n-3 in consequence of the highest 22:6, and the lowest 18:2 in liver phospholipid. But PO lowers the ratio or 20:4/18 more than FO. In conclusion, EPA oil was more effective in lowering serum lipids than FO and PO. Reviewing the dietary effect of fatty acid on eicosanoids composition in rats, it is considered that more possibility was with FO than PO in the effectiveness of atherosclerosis prevention and more with PO than with EPA oil. It was also found that FO showed more effective than EPA oil for atherosclerosis prevention. It was hardly found that CO had any effect on lowering serum lipids and on eicosanoids composition in liver phospholipid for the prevention of atherosclerosis.

• Nuclear Medicine and Molecular Imaging
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• 제40권5호
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• pp.243-248
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• 2006

목적: 다른 기관들에 비해 간에서는 상대적으로 FDG 섭취 양상이 매우 불규칙하며, 악성 병변이 없는 간에서 비정상적으로 FDG 섭취가 증가하기도 한다. 하지만, 이제까지 이러한 다양한 간의 FDG 섭취를 간의 다른 양성 질환과 연관시킨 연구가 없어, 저자들은 이 연구에서 간에서의 FDG 섭취 양상과 지방간, 간 기능 검사, 지질 프로필을 포함하는 다양한 임상 요인과의 관계를 밝히고자 하였다. 대상 및 방법: 건강검진 목적으로 $^{18}F-FDG$ PET/CT를 시행한 188명 (남/여: 120/68, 평균나이: $50{\pm}9$세)을 대상으로 분석하였다. 간의 FDG 섭취에 영향을 줄 수 있는 당뇨 및 내당증 장애 환자, 심한 간질환이나 오랜 약물 복용의 기왕력이 있는 환자는 연구대상에서 제외하였다. PET/CT의 횡단면에서 간의 5번 분절에 해당하는 부위에 관심영역을 설정하고 이 부위의 평균 SUV를 구하여, 지방간이 있는 군과 없는 군 사이의 차이를 분석하였다. 또한 혈중 간 기능(ALT, AST), 알코올성 간질환(${\gamma}-GT$), 총 콜레스테롤, 중성지방 수치와 간의 FDC 섭취와의 관계를 알아보았다. 지방간 환자들의 체질량지수, 음주력을 조사하여 이 인자들이 간의 FDG 섭취에 미치는 영향도 분석하였다 결과 지방간이 있는 군의 평균 SUV가 지방간이 없는 군보다 통계적으로 유의하게 높았다(p<0.05). 혈중 총 콜레스테롤과 중성지방 수치는 간의 FDG 섭취와 유의한 상관관계를 보인 반면, 다른 요인들은 상관관계를 보이지 않았다. 또한, 지방간 환자에서 음주나 체질량 지수의 위험군과 비위험군 사이에 간의 FDG 섭취 정도는 차이는 보이지 않았다. 다변량 분석 결과, 지방간의 유무와 혈중 중성지방 수치가 간의 평균 SUV에 영향을 주는 유의한 독립 인자였다. 결론: 결론적으로 간의 FDG 섭취 정도는 지방간의 유무에 영향을 받으며, 중성지방 수치와 유의한 상관관계를 보였다.

• 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.

• 한국식품과학회지
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• 제10권3호
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• pp.313-319
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• 1978

무지방사료(無脂肪飼料) 및 여기에 17:0, 18:0 혹은 18:2을 첨가(添加)한 사료(飼料)를 병아리에 급여(給與)해서 간장(肝臟) 및 혈장(血漿)의 각지질분획(各脂質分劃)의 지방산조성(脂肪酸組成)에 미치는 급여지방산(給與脂肪酸)의 영향(影響)을 조사(調査)하였다. 그 결과(結果) 간장중(肝臟中)의 총지질함량(總脂質含量) 및 각지질분획(各脂質分劃)의 함량(含量)은 급여지방산(給與脂肪酸)에 의해서 영향(影響)받지 않았다. 그러나 17:0을 급여(給與)하면 간장(肝臟) 및 혈장(血漿)의 각지질분획(各脂質分劃)에 17:0 및 17:1 출현(出現)하고, 혈장(血漿)트리그리세라이드에서는 17:0이 또한 혈장(血漿)콜레스테롤에스텔에서는 17:1이 다른 분획(分劃)보다도 유의(有意)하게 높았다. 더욱이 간장(肝臟)에서는 각분획(各分劃)사이에 양지방산(兩脂肪酸)의 분포치(分布値)에 큰 차이(差異)가 없었다. 18:2의 급여(給與)도 17:0을 급여(給與)한때와 같이 간장(肝臟) 및 혈장(血漿)의 각지질분획(各脂質分劃)에 18:2이 출현(出現)하고, 특(特)히 간장인지질분획(肝臟燐脂質分劃)에서 18:2의 분포치(分布値)는 다른분획(分劃)보다도 유의(有意)하게 높았다. 그러나 18:0을 급여(給與)해도 이것이 간장(肝臟) 및 혈장중(血漿中)에 특별적(特別的)으로 증가(增加)하지는 않았다. 또한 17:0 및 18:2과 같은 외인성지방산(外因性脂肪酸)의 급여(給與)에 의하여 내인적(內因的)으로 합성(合成)되는 16:1 및 18:1의 분포치(分布値)는 간장(肝臟)에서 감소(減少)하는 경향(傾向)을 나타내었다.

• Journal of Ginseng Research
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• 제45권3호
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• pp.380-389
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• 2021

Metabolic syndrome (MS) refers to a clustering of at least three of the following medical conditions: high blood pressure, abdominal obesity, hyperglycemia, low high-density lipoprotein level, and high serum triglycerides. MS is related to a wide range of diseases which includes obesity, diabetes, insulin resistance, cardiovascular disease, dyslipidemia, or non-alcoholic fatty liver disease. There remains an ongoing need for improved treatment strategies for MS. The most important risk factors are dietary pattern, genetics, old age, lack of exercise, disrupted biology, medication usage, and excessive alcohol consumption, but pathophysiology of MS has not been completely identified. Korean Red Ginseng (KRG) refers to steamed/dried ginseng, traditionally associated with beneficial effects such as anti-inflammation, anti-fatigue, anti-obesity, anti-oxidant, and anti-cancer effects. KRG has been often used in traditional medicine to treat multiple metabolic conditions. This paper summarizes the effects of KRG in MS and related diseases such as obesity, cardiovascular disease, insulin resistance, diabetes, dyslipidemia, or non-alcoholic fatty liver disease based on experimental research and clinical studies.

• 대한한방내과학회지
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• 제35권2호
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• pp.184-194
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• 2014

Objectives : This study was designed to investigate the effect on lipoapoptosis of Alisma orientale extract against free fatty acid-induced cellular injury. Methods : HepG2 cells were used in an vitro model. HepG2 cells were treated with free fatty acids to generate a cellular model of nonalcoholic fatty liver disease (NAFLD). Using this cellular model, the anti-apoptotic effect and reducing steatosis of Alisma orientale extract against free fatty acid-induced cellular injury was evaluated by measuring steatosis and apoptosis. Results : Alisma orientale extract significantly attenuated free fatty acid-induced intracellular steatosis. Alisma orientale extract inhibited free fatty acid-mediated activation of pJNK, PUMA, BAX, caspase-3, and -9, and apoptotic kinases that are correlated with NAFLD. Alisma orientale extract also promoted Bcl-2, a anti-apoptotic protein. Conclusions : From the above, the Alisma orientale extract decreased the hepatocyte steatosis and showed the hepatocelluar protective effect by the regulation of apoptosis-related protein. It proposes the possibility of Alisma orientale extract to the treatment of nonalcoholic fatty liver disease in clinics.