• Title/Summary/Keyword: Alcoholic Fatty Liver

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Pharmacological Analyses of HIMH0021 Extracted from Acer Tegmentosum and Efficacy Tests of Steatohepatitis and Hepatic Fibrosis in NASH/ASH (산겨릅나무로부터 추출된 HIMH0021의 알콜성·비알콜성 지방간염 질환에서의 약리학적 분석 및 지방간염 및 간섬유화 억제능 평가)

  • Ji Hoon Yu;Yongjun Lee
    • Proceedings of the Plant Resources Society of Korea Conference
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    • 2021.04a
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    • pp.5-5
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    • 2021
  • Alcoholic and nonalcoholic steaohepatitis is a leading form of chronic liver disease with few biomakers ad treatment options currently available. a progressive disease of NAFLD may lead to fibrosis, cirrhosis, and hepatocellular carcinoma. Recently, we extracted HIMH0021, which is an active flavonoid component in the Acer tegmentosum extract, has been shown to protect against liver damage caused by hepatic dysfunction. Therefore, in this study, we aimed to investigate whether HIMH0021 could regulate steatohepatitis and liver fibrosis during alcoholic or nonalcoholic metabolic process. HIMH0021, which was isolated from the active methanol extract of A. tegmentosum, inhibited alcohol-induced steatosis and attenuated the serum levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) during hepatocellular alcohol metabolism, both of which promote lipogenesis as well as liver inflammation. Treatment with HIMH0021 conferred protection against lipogenesis and liver injury, inhibited the expression of cytochrome P4502E1, and increased serum adiponectin levels in the mice subjected to chronic-plus-binge feeding. Furthermore, in hepatocytes, HIMH0021 activated fatty acid oxidation by activating pAMPK, which comprises pACC and CPT1a. These findings suggested that HIMH0021 could be used to target a TNFα-related pathway for treating patients with alcoholic hepatitis.

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Role of Tumor Necrosis Factor-${\alpha}$ Promoter Polymorphism and Insulin Resistance in the Development of Non-alcoholic Fatty Liver Disease in Obese Children

  • Yang, Hye-Ran;Ko, Jae-Sung;Seo, Jeong-Kee
    • Pediatric Gastroenterology, Hepatology & Nutrition
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    • v.15 no.1
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    • pp.44-51
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    • 2012
  • Purpose: Tumor necrosis factor-${\alpha}$ (TNF-${\alpha}$) polymorphism has been suggested to play an important role in the pathogenesis of non-alcoholic fatty liver disease (NAFLD) in obese adults, and known to be a mediator of insulin resistance. In this study, we evaluated the role of TNF-${\alpha}$ promoter polymorphisms and insulin resistance in the development of NAFLD in obese children. Methods: A total of 111 obese children (M:F=74:37; mean age, $11.1{\pm}2.0$ yrs) were included. The children were divided into 3 groups: controls (group I, n=61), children with simple steatosis (group II, n=17), and children with non-alcoholic steatohepatitis (group III, n=33). Serum TNF-${\alpha}$ levels, homeostasis model assessment of insulin resistance (HOMA-IR), and TNF-${\alpha}$ -308 and -238 polymorphisms were evaluated. Results: There were no differences in TNF-${\alpha}$ polymorphism at the -308 or the -238 loci between group I and group II + III ($p$=0.134 and $p$=0.133). The medians of HOMA-IR were significantly different between group I and group II + III ($p$=0.001), with significant difference between group II and group III ($p$=0.007). No difference was observed in the HOMA-IR among the genotypes at the -308 locus ($p$=0.061) or the -238 locus ($p$=0.207) in obese children. Conclusion: TNF-${\alpha}$ promoter polymorphisms at the -308 and -238 loci were not significantly associated with the development of NAFLD in children; nevertheless, insulin resistance remains a likely essential factor in the pathogenesis of NAFLD in obese children, especially in the progression to NASH.

The Effect of Bangpungtongsungsan on Insulin Resistance Induced by Non-alcoholic Fatty Liver Disease (NAFLD) (방풍통성산의 지방대사조절을 통한 비알콜성 지방간 유도 인슐린저항성 개선 효과)

  • Seo, Il-bok;Ahn, Sang Hyun;Kim, Ki Bong
    • The Journal of Pediatrics of Korean Medicine
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    • v.32 no.4
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    • pp.1-12
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    • 2018
  • Objectives Bangpungtongsungsan is an herbal medicine that treats obesity and dampness-phlegm. The aim of this study was to investigate the efficacy of Bangpungtongsungsan on insulin resistance induced by non-alcoholic fatty liver disease. Methods Male 6-week-old C57BL/6 male mice were divided into four groups: control group (Ctrl), high fat diet group (HFF), high fat diet with Bangpungtongsungsan extract administration group (BT1), and high fat diet with double concentration of Bangpungtongsungsan extract administration group (BT2). Each 10 mice were allocated to each group (total of 40 mice). All mice were allowed to eat fat rich diet freely throughout the experiment. To examine the effect of Bangpungtongsungsan, we observed weight changes, lipid blot distributions, PGC-1, $p-I{\kappa}B$, 8-OHdG, p-JNK, total cholesterol and glucose levels. Results Comparing of body weight measurements between 4 groups, weight gain was significantly lower in BT1 and BT2 group than the HFF group. The distribution of lipid blots and positive reaction of PGC-1 were significantly lower in BT1 and BT2 group. The positive reaction of $p-I{\kappa}B$ and 8-OHdG in hepatic tissues was significantly lower in BT1 and BT2 group. The positive reaction of p-JNK in hepatic tissues was significantly lower in BT1 and BT2 group. Total cholesterol and glucose levels were significantly lower in BT1 and BT2 group. Conclusions Bangpungtongsungsan has the effect of improving non-alcoholic fatty liver induced insulin resistance through regulation of lipid metabolism.

Impact of dietary fiber intake on non-alcoholic fatty liver disease risk in Korean patients with obesity and type 2 diabetes mellitus

  • Ji-Sook Park;Hina Akbar;Young-Seol Kim;Jung-Eun Yim
    • Journal of Nutrition and Health
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    • v.57 no.3
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    • pp.282-291
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    • 2024
  • Purpose: Korean patients with type 2 diabetes mellitus (T2DM) and obesity are at a high risk of developing severe non-alcoholic fatty liver disease (NAFLD). This study examined the dietary intakes and compared the risks of NAFLD-related complications in Korean patients with T2DM and obesity. Methods: Data from the Korean National Diabetes Program cohort were used to study patients with T2DM. Two hundred and sixty-five obese patients with T2DM (body mass index ≥ 25 kg/m2) were classified into NAFLD and non-NAFLD groups. The nutrient intake was analyzed using a 24-hour dietary recall questionnaire. Anthropometric and biochemical data were also obtained. Statistical analyses were performed to determine the significant differences between the 2 groups. Results: The serum gamma-glutamyl transpeptidase levels in obese patients with T2DM and NAFLD were significantly higher than in obese T2DM patients without NAFLD (p < 0.05). The serum glucose and lipid profiles showed no significant differences between the NAFLD and non-NAFLD groups. The carbohydrate, protein, and fat levels also did not differ significantly. The results showed that the fiber intake of the NAFLD and non-NAFLD groups was 14.11 ± 3.86 g/100 kcal and 15.70 ± 4.56 g/1,000 kcal, respectively, showing that the dietary fiber intake of the non-NAFLD group was significantly higher (p < 0.05). A correlation was observed between total fiber intake and γ-glutamyl transpeptidase in either patient group. In addition, the odds ratio of developing NAFLD was 0.29× lower when the fiber was consumed at 125% of adequate intake. Conclusions: A higher dietary fiber intake may reduce the risk of NAFLD in obese patients with T2DM. The dietary intake of Korean obese patients with T2DM should include and be enriched in dietary fiber to aid in preventing and treating NAFLD.

Identifying Classes for Classification of Potential Liver Disorder Patients by Unsupervised Learning with K-means Clustering (K-means 클러스터링을 이용한 자율학습을 통한 잠재적간 질환 환자의 분류를 위한 계층 정의)

  • Kim, Jun-Beom;Oh, Kyo-Joong;Oh, Keun-Whee;Choi, Ho-Jin
    • Proceedings of the Korean Information Science Society Conference
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    • 2011.06c
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    • pp.195-197
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    • 2011
  • This research deals with an issue of preventive medicine in bioinformatics. We can diagnose liver conditions reasonably well to prevent Liver Cirrhosis by classifying liver disorder patients into fatty liver and high risk groups. The classification proceeds in two steps. Classification rules are first built by clustering five attributes (MCV, ALP, ALT, ASP, and GGT) of blood test dataset provided by the UCI Repository. The clusters can be formed by the K-mean method that analyzes multi dimensional attributes. We analyze the properties of each cluster divided into fatty liver, high risk and normal classes. The classification rules are generated by the analysis. In this paper, we suggest a method to diagnosis and predict liver condition to alcoholic patient according to risk levels using the classification rule from the new results of blood test. The K-mean classifier has been found to be more accurate for the result of blood test and provides the risk of fatty liver to normal liver conditions.

Difference in Serum Iron, Cardiac, and Biochemical Indices between Alcoholic and Non-alcoholic Fatty Liver (알코올성 지방간과 비알코올성 지방간 성인에 있어 혈청 철 표지자, 심장 표지자, 생화학적 표지자의 차이)

  • Kim, Cheol-Yu;Moon, Seong-Min;Hyun, Kyung-Yae;Kim, Dae-Sik;Choi, Seok-Cheol
    • Journal of Life Science
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    • v.19 no.2
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    • pp.185-191
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    • 2009
  • Although alcohol drinking may cause fatty liver to induce hepatocytic injury, other factors lead to it. We designed this study to investigate the differences in serum iron, cardiac, and biochemical indices in men with fatty liver and the difference between alcohol drinkers (Alcohol group) and non-drinkers (Non-alcohol group). The alcohol group had higher body indices than the non-alcohol group. Systolic and diastolic blood pressure (SBP and DBP), and right and left intraocular pressure in the alcohol group were higher than those in the non-alcohol group. Hemoglobin, hematocrit, mean corpuscular hemoglobin, mean corpuscular hemoglobin concentration, and monocyte counts were higher in the alcohol group than in the non-alcohol group. Alanine aminotransferase, ${\gamma}$-glutamyltranspeptidase, total cholesterol, triglyceride, low-density lipoprotein cholesterol, glucose, creatinine, uric acid, iron, total iron binding capacity, and ferritin levels in the alcohol group were greater than those in the non-alcohol group. The present data reveals that alcohol-induced fatty liver has more elevated level of iron indices than in non-alcohol fatty liver as well as biochemical and cardiac indices, indicating that alcohol- induced fatty liver may cause possibility of adult diseases including cardiovascular disease and metabolic syndrome.

Central energy metabolism remains robust in acute steatotic hepatocytes challenged by a high free fatty acid load

  • Niklas, Jens;Bonin, Anne;Mangin, Stefanie;Bucher, Joachim;Kopacz, Stephanie;Matz-Soja, Madlen;Thiel, Carlo;Gebhardt, Rolf;Hofmann, Ute;Mauch, Klaus
    • BMB Reports
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    • v.45 no.7
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    • pp.396-401
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    • 2012
  • Overnutrition is one of the major causes of non-alcoholic fatty liver disease (NAFLD). NAFLD is characterized by an accumulation of lipids (triglycerides) in hepatocytes and is often accompanied by high plasma levels of free fatty acids (FFA). In this study, we compared the energy metabolism in acute steatotic and non-steatotic primary mouse hepatocytes. Acute steatosis was induced by pre-incubation with high concentrations of oleate and palmitate. Labeling experiments were conducted using [$U-^{13}C_5$,$U-^{15}N_2$] glutamine. Metabolite concentrations and mass isotopomer distributions of intracellular metabolites were measured and applied for metabolic flux estimation using transient $^{13}C$ metabolic flux analysis. FFAs were efficiently taken up and almost completely incorporated into triglycerides (TAGs). In spite of high FFA uptake rates and the high synthesis rate of TAGs, central energy metabolism was not significantly changed in acute steatotic cells. Fatty acid ${\beta}$-oxidation does not significantly contribute to the detoxification of FFAs under the applied conditions.

6-O-Galloylsalidroside, an Active Ingredient from Acer tegmentosum, Ameliorates Alcoholic Steatosis and Liver Injury in a Mouse Model of Chronic Ethanol Consumption

  • Kim, Young Han;Woo, Dong-Cheol;Ra, Moonjin;Jung, Sangmi;Kim, Ki Hyun;Lee, Yongjun
    • Natural Product Sciences
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    • v.27 no.3
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    • pp.201-207
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    • 2021
  • We have previously reported that Acer tegmentosum extract, which is traditionally used in Korea to reduce alcohol-related liver injury, suppresses liver inflammation caused by excessive alcohol consumption and might improve metabolism. The active ingredient, 6-O-galloylsalidroside (GAL), was isolated from A. tegmentosum, and we hypothesized that GAL could provide desirable pharmacological benefits by ameliorating physiological conditions caused by alcohol abuse. Therefore, this study focused on whether GAL could ameliorate alcoholic fat accumulation and repair liver injury in mice. During chronic alcohol consumption plus binge feeding in mice, GAL was administered orally once per day for 11 days. Intrahepatic lipid accumulation was measured in vivo using a noninvasive method, 1H magnetic resonance imaging, and confirmed by staining with hematoxylin and eosin and Oil Red O. The serum levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were measured using a Konelab system, and the triglyceride content was measured in liver homogenates using an enzymatic peroxide assay. The results suggested that GAL alleviated alcohol-induced steatosis,e as indicated by decreased hepatic and serum triglyceride levels in ethanol-fed mice. GAL treatment also correlated with a decrease in the Cd36 mRNA expression, thus potentially inhibiting the development of alcoholic steatosis via the hepatic de novo lipogenesis pathway. Furthermore, treatment with GAL inhibited the expression of cytochrome P450 2E1 and attenuated hepatocellular damage, as reflected by a reduction in ALT and AST levels. These findings suggest that GAL extracted from A. tegmentosum has the potential to serve as a bioactive agent for the treatment of alcoholic fatty liver and liver damage.

The Effects of Electroacupuncture for Treatment of Patients with Non-Alcoholic Fatty Liver Disease: Prospective Randomized Controlled Study (알코올성 지방간 환자에 있어 전침 치료의 효과: 무작위 배정 대조군 연구)

  • Lee, Chang-Hyeong;Kim, Byung-Seok;Choi, Ae-Ryun;Kim, Kyung-Soon;Kwak, Min-A;Kim, Seung-Mo
    • Journal of Korean Medicine for Obesity Research
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    • v.15 no.1
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    • pp.1-8
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    • 2015
  • Objectives: The aim of this study was to evaluate the effectiveness and safety of electroacupuncture for non-alcoholic fatty liver disease (NAFLD). Methods: A randomized, controlled pilot trial was conducted. Twenty-two participants were randomized into one of the two groups: an acupuncture group (n=11) and wait-list group (n=11). The treatment group received 8 sessions of electroacupuncture over 8 weeks. Twenty points (CV4, CV12, both LR14, GB26, ST25, ST34, ST40, ST36, SP4, SP6, LR3) were selected for needling. The control group did not receive acupuncture treatment during study period and followup were done in the 4th and 8th weeks after randomization in both groups. The primary outcome was body fat computed tomography and the secondary outcomes included blood test (aspartate aminotransferase, alanine transferase, triglyceride, total cholesterol, high density lipoproteincholesterol, low density lipoprotein-cholesterol, blood sugar test, ${\gamma}$-guanosine triphosphate) and body composition test (body mass index, weight, body fat mass, body fat rate, waist hip ratio). Safety was assessed at every visit. Results: There was no significant differences in between the experimental group and control group. There were no adverse events. Conclusions: The results suggest that In patients with NAFLD, electroacupuncture treatment did not induce worsening of liver disease and liver function, but it was no improvement symptoms of fatty liver. Study of herb medicine treatments and other acupuncture therapy of NAFLD are required later.

Improvement Effect of Non-alcoholic Fatty Liver Disease by Curcuma longa L. Extract (강황 추출물의 비알코올성 지방간 질환 개선 효과)

  • Lee, Young Seob;Lee, Dae Young;Kwon, Dong Yeul;Kang, Ok Hwa
    • Korean Journal of Medicinal Crop Science
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    • v.28 no.4
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    • pp.276-286
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    • 2020
  • Background: Non-alcoholic fatty liver disease (NAFLD) is a chronic liver disease associated with multiple metabolic disorders. The medicinal plant Curcuma longa L. is widely distributed in Asia and has been used to treat a spectrum diseases in clinical practice. To date, there are inadequate reports of the effects of C. longa 50% EtOH extract (CE) on NAFLD. Therefore, in this study, we evaluate the CE on an NAFLD animal and elucidate the mechanism of action. Methods and Results: C57BL/6J mice fed a methionine-choline deficient diet (MCD) were treated with CE or milk thistle, and changes in inflammation and stetosis were assessed. Experimental animals were divided into six group (n = 10); Normal, MCD, MCD + CE 50 mg/kg/day (CE 50), MCD + CE 100 mg/kg/day (CE 100), MCD + CE 150 mg/kg/day (CE 150), and the Control, MCD + Milk thistle 150 mg/kg/day (MT 150). Body weight, liver weight, liver function, and histological changes were assessed in experimental animals. Quantitative real-time polymerase chain reaction and western blot analyses were performed on samples collected after 4 weeks of treatment. We observed that CE administration improved MCD-diet-induced lipid accumulation, and triglyceride (TG) and total cholesterol (TC) levels in serum. Treatment with CE also decreased hepatic lipogenesis through modulation of the sterol regulatory element binding protein-1 (SREBP-1), CCAAT-enhancer binding protein α (C/EBPα), fatty acid synthase (FAS), and peroxisome proliferator-activated receptor γ (PPARγ) expresion. In addition, the use of CE increased adenosine monophosphate-activated protein kinase (AMPK) phosphorylation and inhibited the up-regulation of toll-like receptor (TLR)-2 and TLR-4 signaling and the production of inflammatory mediators. Conclusions: In this report, we observed that CE regulated lipid accumulation in an MCD dietinduced NAFLD model by decreasing lipogenesis. These data suggeste that CE could effectively protect mice against MCD-induced NAFLD, by inhibiting the TLR-2 and TLR-4 signaling cascades.