• Journal of Nutrition and Health
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• 제21권3호
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• pp.154-163
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• 1988

Effects of alchohol and fat content in a balanced diet on chemical composition and morphology of liver were investigated in growing rats. Fourth eight male rats of Sprague-Dawley strain weighing about 160g were divided into 4 groups ; high fat diet group, alcohol-administered high fat diet group, low fat diet group and alcohol-administered high fat diet group, low fat diet group and alcohol-administered low fat diet group. High and low fat diets supplied 30% and 12%, respectively, of total calorie intake from fat, and alcohol was given by adding ethanol in drinking waster at 10%. Diets contained adequate amounts of all nutrients required for rats, including lipotrpoic agents(choline and methionine) to minimize effects of factors other than alcohol on liver damage. Ratios of liver weight to body weight were statistically different among groups. Liver/dody weight ratios alcohol-administered rats were significantly higher than those of non-alcohol groups after 6 weeks treatment. Although total lipid and triglyceride per gram liver were increased in alcohol-administered rats, especially low fat diet fed rats, the values were not significantly different. Opticmicroscopical observation revealed increase in cell size and no change in morphology of liver. Examination of hepatocytes by electron microscopy showed that fat droplets were observed in all groups but enlarged in the alcohol-administered low fat diet fed rat. Contents of protein, cholesterol and phospholipid were not affected by alcohol consumption. The level of lipid peroxide was significantly lower in the livers of alcohol-administered rats than in the livers of non-alcohol groups. The results of this study indicate that even moderate alcohol drinking and dietary fat content did not affect any significant change in composition and morphology of liver until 6 week treatment but that even moderate alcohol drinking caused some signs of steatosis of liver.

• 한국식품과학회지
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• 제46권6호
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• pp.762-768
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• 2014

본 연구에서는 oleic acid로 유도시킨 비알코올성 지방간 HepG2 세포 모델을 활용하여 LAFGE의 비알코올성 지방간 개선 효과를 검토하고 RT-PCR과 Western blot으로 메카니즘을 해석하였다. LAFGE는 1 mg/mL 농도에서 NFGE보다 세포 내 지방축적을 약 1.5배 저해하였다. Fig. 5에 나타낸 바와 같이 LAFGE는 FAT/CD36 mRNA 발현을 감소시켜 세포 내로 유입되는 지방산의 양을 감소시켰으며, $PPAR{\alpha}$와 CPT-1의 mRNA 발현을 증강시킴으로써 지방산의 베타-산화를 촉진시켰다. 또한 LAFGE는 지방합성을 촉진하는 전사인자인 SREBP-1c와 그의 조절을 받는 FAS의 mRNA 발현 수준을 oleic acid 처리시보다 각각 51%와 35%까지 크게 감소시켰다. 뿐만 아니라 LAFGE는 농도의존적으로 SREBP-1c와 FAS의 단백질 발현도 감소시켰다. 이 결과들은 LAFGE가 oleic acid처리에 의해 유도된 HepG2 세포 내의 지방축적을 개선할 수 있음을 시사하였다.

• The Korean Journal of Physiology and Pharmacology
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• 제24권5호
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• pp.385-394
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• 2020

Eupatilin is known to possess anti-apoptotic, anti-oxidative, and anti-inflammatory properties. We report here that eupatilin has a protective effect on the ethanol-induced injury in rats. Sprague-Dawley rats were divided into 6 groups: control, vehicle, silymarin, eupatilin 10 mg/kg, eupatilin 30 mg/kg, and eupatilin 100 mg/kg. Plasma levels of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) were analyzed to determine the extent of liver damage. Total cholesterol (TC) and triglycerides (TG) were analyzed to determine the level of liver steatosis. Malondialdehyde level, superoxide dismutase (SOD) activity, and glutathione (GSH) level were analyzed to determine the extent of oxidative stress. Tumor necrosis factor (TNF)-α and interleukin (IL)-1β were quantified to verify the degree of inflammation. Based on our findings, chronic alcohol treatment significantly changed the serum indexes and liver indicators of the model rats, which were significantly improved by eupatilin treatment. Rats in the eupatilin-treatment group showed reduced levels of AST, ALT, TG, TC, TNF-α, and IL-1β, increased SOD activity and GSH levels, and improved overall physiology compared to the alcoholic liver disease model rats. H&E staining also verified the eupatilin-mediated improvement in liver injury. In conclusion, eupatilin inhibits alcohol-induced liver injury via its antioxidant and anti-inflammatory effects.

• Pediatric Gastroenterology, Hepatology & Nutrition
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• 제24권5호
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• pp.443-454
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• 2021

Purpose: Due to the increasing prevalence of obesity worldwide, non-alcoholic fatty liver disease (NAFLD) has reached epidemic dimensions over time. NAFLD is the most common cause of childhood chronic liver disease. There is a relationship between NAFLD and oxidative stress. This study aims to investigate the changes in thiol/disulfide homeostasis parameters to determine the oxidant/antioxidant balance in obese rats with diet-induced NAFLD and healthy rats. Methods: Twelve Wistar albino rats were used in this study. Experimentally produced NAFLD obese rats (n=6) and healthy rats were compared. Experimental NAFLD model was created with a special fatty liver diet (Altromin^® C1063, Fatty Liver Diet, Exclusivet, Lage, Germany). The biochemical and histopathological features of the groups, as well as serum thiol/disulfide homeostasis parameters, were analyzed and compared. Results: In the experimentally induced NAFLD rat model, they gained more weight than the control group. Steatosis (at least grade 2) occurred in all rats fed with special fatty liver diet for 12 weeks. Histopathologically, no high-grade inflammation was observed in rats with experimental NAFLD after feeding a diet for 12 weeks. Results revealed that aspartate transaminase and alanine transaminase levels were high, albumin levels were low, oxidant stress parameters increased, and antioxidant thiol groups decreased. Conclusion: Experimental NAFLD is characterized by increased oxidant stress accompanying fatty tissue in the liver. Analysis of thiol/disulfide homeostasis parameters in NAFLD can be used in further studies to develop effective treatment options.

• 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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• 제25권3호
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• pp.240-250
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• 2022

Purpose: This study aimed to examine the advantages and usefulness of transient elastography (Fibroscan^®) in diagnosing non-alcoholic steatohepatitis in children and adolescents compared to those of abdominal computed tomography and liver ultrasonography. Methods: Forty-six children and adolescent participants aged between 6 and 16 years who underwent transient elastography (Fibroscan^®) as well as liver ultrasonography or abdominal computed tomography were included. Thirty-nine participants underwent liver ultrasonography and 11 underwent computed tomography. The physical measurements, blood test results, presence of metabolic syndrome, and the degree of liver steatosis and liver fibrosis were analyzed, and their correlations with transient elastography (Fibroscan^®), abdominal computed tomography, and liver ultrasonography, as well as the correlations between examinations, were analyzed. Results: Thirty-six participants (78.3%) were boys, and the mean age was 12.29±2.57 years, with a mean body mass index of 27.88±4.28. In the 46 participants, the mean values for aspartate aminotransferase, alanine aminotransferase, and total bilirubin were 89.87±118.69 IU/L, 138.54±141.79 IU/L, and 0.77±0.61 mg/dL, respectively. Although transient elastography (Fibroscan^®) and abdominal computed tomography grading had a statistically significant positive correlation with aspartate aminotransferase and alanine aminotransferase values, the correlations between the results of grading performed by transient elastography (Fibroscan^®), abdominal computed tomography, and liver ultrasonography were not statistically. Conclusion: We confirmed that each examination was correlated with the results of some blood tests, suggesting the usefulness and possibility of diagnosis and treatment of steatohepatitis mediated by transient elastography (Fibroscan^®) in the department of pediatrics.

• Nutrition Research and Practice
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• 제11권2호
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• pp.105-113
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• 2017

BACKGROUND/OBJECTIVES: A high-fat diet (HFD) induces obesity, which is a major risk factor for cardiovascular disease and cancer, while a calorie-restricted diet can extend life span by reducing the risk of these diseases. It is known that health effects of diet are partially conveyed through epigenetic mechanism including DNA methylation. In this study, we investigated the genome-wide hepatic DNA methylation to identify the epigenetic effects of HFD-induced obesity. MATERIALS AND METHODS: Seven-week-old male C57BL/6 mice were fed control diet (CD), calorie-restricted control diet (CRCD), or HFD for 16 weeks (after one week of acclimation to the control diet). Food intake, body weight, and liver weight were measured. Hepatic triacylglycerol and cholesterol levels were determined using enzymatic colorimetric methods. Changes in genome-wide DNA methylation were determined by a DNA methylation microarray method combined with methylated DNA immunoprecipitation. The level of transcription of individual genes was measured by real-time PCR. RESULTS: The DNA methylation statuses of genes in biological networks related to lipid metabolism and hepatic steatosis were influenced by HFD-induced obesity. In HFD group, a proinflammatory Casp1 (Caspase 1) gene had hypomethylated CpG sites at the 1.5-kb upstream region of its transcription start site (TSS), and its mRNA level was higher compared with that in CD group. Additionally, an energy metabolism-associated gene Ndufb9 (NADH dehydrogenase 1 beta subcomplex 9) in HFD group had hypermethylated CpG sites at the 2.6-kb downstream region of its TSS, and its mRNA level was lower compared with that in CRCD group. CONCLUSIONS: HFD alters DNA methylation profiles in genes associated with liver lipid metabolism and hepatic steatosis. The methylation statuses of Casp1 and Ndufb9 were particularly influenced by the HFD. The expression of these genes in HFD differed significantly compared with CD and CRCD, respectively, suggesting that the expressions of Casp1 and Ndufb9 in liver were regulated by their methylation statuses.

• Journal of Ginseng Research
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• 제43권2호
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• pp.196-208
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• 2019

Background: Nonalcoholic steatohepatitis (NASH) is one of the chronic inflammatory liver diseases and a leading cause of advanced liver fibrosis, cirrhosis, and hepatocellular carcinoma. The main purpose of this study was to clarify the effects of GBCK25 fermented by Saccharomyces servazzii GB-07 and pectinase, on NASH severity in mice. Methods: Six-wk-old male mice were fed either a normal diet (ND) or a Western diet (WD) for 12 wks to induce NASH. Each group was orally administered with vehicle or GBCK25 once daily at a dose of 10 mg/kg, 20 mg/kg, 100 mg/kg, 200 mg/kg, or 400 mg/kg during that time. The effects of GBCK25 on cellular damage and inflammation were determined by in vitro experiments. Results: Histopathologic analysis and hepatic/serum biochemical levels revealed that WD-fed mice showed severe steatosis and liver injury compared to ND-fed mice. Such lesions were significantly decreased in the livers of WD-fed mice with GBCK25 administration. Consistently, mRNA expression levels of NASH-related inflammatory-, fibrogenic-, and lipid metabolism-related genes were decreased in the livers of WD-fed mice administered with GBCK25 compared to WD-fed mice. Western blot analysis revealed decreased protein levels of cytochrome P450 2E1 (CYP2E1) with concomitantly reduced activation of c-Jun N-terminal kinase (JNK) in the livers of WD-fed mice administered with GBCK25. Also, decreased cellular damage and inflammation were observed in alpha mouse liver 12 (AML12) cells and RAW264.7 cells, respectively. Conclusion: Administration of GBCK25 ameliorates NASH severity through the modulation of CYP2E1 and its associated JNK-mediated cellular damage. GBCK25 could be a potentially effective prophylactic strategy to prevent metabolic diseases including NASH.

• Nutrition Research and Practice
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• 제17권6호
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• pp.1084-1098
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• 2023

BACKGROUND/OBJECTIVES: Previous research has shown maternal betaine supplementation alleviates fetal-derived hepatic steatosis. Therefore, this study examined the anti-inflammatory effect of maternal betaine intake in offspring mice and its mechanism. MATERIALS/METHODS: Female C57BL/6J mice and their offspring were randomly divided into 3 groups according to the treatment received during gestation and lactation: control diet (CD), fatty liver disease (FLD), and fatty liver disease + 1% betaine (FLD-BET). The FLD group was given a high-fat diet and streptozotocin (HFD + STZ), and the FLD-BET group was treated with HFD + STZ + 1% betaine. After weaning, the offspring mice were given a normal diet for 5 weeks and then dissected to measure the relevant indexes. RESULTS: Compared to the CD group, the offspring mice in the FLD group revealed obvious hepatic steatosis and increased serum levels of alanine aminotransferase, interleukin (IL)-6, and tumor necrosis factor (TNF)-α; maternal betaine supplementation reversed these changes. The hepatic mRNA expression levels of IL-6, IL-18, and Caspase-1 were significantly higher in the FLD group than in the CD group. Maternal betaine supplementation reduced the expression of IL-1β, IL-6, IL-18, and apoptosis-associated speck-like protein containing C-terminal caspase recruitment domain (ASC). Maternal betaine supplementation also reversed the increasing protein expressions of nitric oxide dioxygenase-like receptor family pyrin domain containing 3 (NLRP3), ASC, Caspase-1, IL-1β, and IL-18 in offspring mice exposed to HFD + STZ. Maternal betaine supplementation decreased the homocysteine (Hcy) and s-adenosine homocysteine (SAH) levels significantly in the livers. Furthermore, the hepatic Hcy concentrations showed significant inverse relationships with the mRNA expression of TNF-α, NLRP3, ASC, and IL-18. The hepatic SAH concentration was inversely associated with the IL-1β mRNA expression. CONCLUSIONS: The lipotropic and anti-inflammatory effect of maternal betaine supplementation may be associated with the inhibition of NLRP3 inflammasome in the livers of the offspring mice.

• Pediatric Gastroenterology, Hepatology & Nutrition
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• 제23권3호
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• pp.276-285
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• 2020

Purpose: Non-alcoholic fatty liver disease (NAFLD) ranges in severity from simple steatosis to steatohepatitis. Early detection of NAFLD is important for preventing the disease from progressing to become an irreversible end-stage liver disease. We developed a nomogram that allows for non-invasive screening for NAFLD in obese children. Methods: Anthropometric and laboratory data of 180 patients from our pediatric obesity clinic were collected. Diagnoses of NAFLD were based on abdominal ultrasonographic findings. The nomogram was constructed using predictors from a multivariate analysis of NAFLD risk factors. Results: The subjects were divided into non-NAFLD (n=67) and NAFLD groups (n=113). Factors, including sex, body mass index, abdominal circumference, blood pressure, insulin resistance, and levels of aspartate aminotransferase, alanine aminotransferase (ALT), γ-glutamyl transpeptidase (γGT), uric acid, triglycerides, and insulin, were significantly different between the two groups (all p<0.05) as determined using homeostatis model assessment of insulin resistance (HOMA-IR). In our multivariate logistic regression analysis, elevated serum ALT, γGT, and triglyceride levels were significantly related to NAFLD development. The nomogram was established using γGT, uric acid, triglycerides, HOMA-IR, and ALT as predictors of NAFLD probability. Conclusion: The newly developed nomogram may help predict NAFLD risk in obese children. The nomogram may also allow for early NAFLD diagnosis without the need for invasive liver biopsy or expensive liver imaging, and may also allow clinicians to intervene early to prevent the progression of NAFLD to become a more advanced liver disease.