• Journal of Nutrition and Health
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• v.30 no.10
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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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• v.54 no.6
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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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• v.24 no.3
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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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• v.27 no.4
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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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• v.27 no.6
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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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• v.40 no.5
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• pp.243-248
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• 2006

Purpose: Liver demonstrates heterogeneous FDG uptake and sometimes it shows abnormally increased uptake even though there is no malignant tissue. However, there was no previous study to correlate these various pattern of hepatic FDG uptake with benign liver disease. Therefore, we evaluated the significance of hepatic FDG uptake associated with various clinical factors including fatty liver, liver function tests and lipid profiles. Materials and Methods: We reviewed a total of 188 patients (male/female: 120/68, mean age: $50{\pm}9$) who underwent PET/CT for screening of malignancy. Patients with DM, impaired glucose tolerance, previous severe hepatic disease or long-term medication history were excluded. The FDG uptake in liver was analyzed semi-quantitatively using ROI on transaxial images (segment 8) and we compared mean standardized uptake value (SUV) between fatty liver and non-fatty liver group. We also evaluated the correlation between hepatic FDG uptake and various clinical factors including serum liver function test (ALT, AST), ${\gamma}-GT$, total cholesterol and triglyceride concentration. The effect of alcoholic history and body mass index on hepatic FDG uptake was analyzed within the fatty liver patients. Results: The hepatic FDG uptake of fatty liver group was significantly higher than that of non-fatty liver group. Serum total cholesterol and triglyceride concentration showed significant correlation with hepatic FDG uptake. However, there was no significant correlation between other factors (ALT, AST, and ${\gamma}-GT$) and FDG uptake. Also there was no difference of mean SUV between normal and abnormal groups on the basis of alcoholic history and body mass Index within fatty liver patients. Fatty liver and high serum triglyceride concentration were the independent factors affecting hepatic FDG uptake according to multivariate analysis. Conclusion: In conclusion, hepatic FDG uptake was strongly correlated with fatty liver and serum triglyceride concentration.

• Molecules and Cells
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• v.44 no.2
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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.

• Korean Journal of Food Science and Technology
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• v.10 no.3
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• pp.313-319
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• 1978

In order to investigate the effect of dietary long chain fatty acids on fatty acid biosynthesis of liver in birds, single comb White Leghron male chicks were fed a fat-free diet an diets containing margaric, stearic and linoleic acids and liver lipid components and liver and plasma fatty acid distributions were compared. Total lipids of tissues were extracted with a chloroform-methanol mixture. The lipid components were determined by thin layer chromatography and fatty acid distribution of lipid fractions were determined by gas liquid chromatography. Fatty acid feeding did not affect liver lipid components. When margaric acid(17 : 0), was fed, 17:0 and heptadecenoic acid(17:1) appeared in every lipid fractions of liver and plasma, and distribution values of these acids were not significantly different between the lipid fractions of liver. In blood plasma of the 17 : 0 fed chicks, however, significantly higher distribution values of 17 : 0 and 17.1 were observed in the triglyceride fraction and in the cholesterol ester fraction, respectively. Dietary stearic acid (18 : 0) did not show any effect on the distribution of 18 : 0 in every lipid fractions of liver but showed a significantly higher distribution value of 18 : 0 in the free fatty acid fraction of plasma. When linoleic acid (18 : 2) was fed, every lipid fractions of liver and plasma contained 18 : 2, especially a significantly higher distribution value was observed in the phospholipid fraction of liver. Dietary margaric and linoleic acids tended to decrease the distribution value of endogenously synthesized palmitoleic (16 : 1) and oleic (18 : 1) acids in liver.

• Journal of Ginseng Research
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• v.45 no.3
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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.

• The Journal of Internal Korean Medicine
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• v.35 no.2
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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.