• 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.

• Toxicological Research
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• 제35권4호
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• pp.403-410
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• 2019

Curcumin, a hydrophobic polyphenol isolated from the Curcuma longa L. plant, has many pharmacological properties, including antioxidant, anti-inflammatory, and chemo-preventive activities. Curcumin has been shown to have potential in preventing nonalcoholic fatty liver disease (NAFLD). However, the low bioavailability of curcumin has proven to be a major limiting factor in its clinical adoption. Theracurmin, a highly bioavailable curcumin that utilizes micronized technology showed improved biological absorbability in vivo. The aim of this study was to investigate the role of theracurmin in modulating hepatic lipid metabolism in vivo. A fatty liver mouse model was produced by feeding mice a high fat diet (HFD; 60% fat) for 12 weeks. We found that treatment for 12 weeks with theracurmin significantly lowered plasma triacylglycerol (TG) levels and reduced HFD-induced liver fat accumulation. Theracurmin treatment lowered hepatic TG and total cholesterol (T-CHO) levels in HFD-fed mice compared to controls. In addition, theracurmin administration significantly reduced lipid peroxidation and cellular damage caused by reactive oxygen species in HFD-fed mice. Overall, these results suggest that theracurmin has the ability to control lipid metabolism and can potentially serve as an effective therapeutic remedy for the prevention of fatty liver.

• 한국방사선학회논문지
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• 제12권5호
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• pp.623-630
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• 2018

비알코올성 지방간 질환은 만성 간질환의 가장 흔한 원인이다. 이 연구의 목적은 비알코올성 지방간 질환 동물모델을 확립하고 생체 내 짧은 양성자 자기공명분광법을 이용하여 비침습적으로 간의 대사물질과 지질의 변화를 정량 분석하고자 하였다. 각 실험은 고지방식 먹이를 먹고 나서 0주를 기준선으로 하고, 2, 4, 6, 8주에 쥐의 간 실질 조직으로부터 측정되었다. 0주를 기준선으로 하고 2주와 비교했을 때 0.9, 1.3, 2.3, 2.8 및 5.3 ppm 에서 유의미하게 증가하였다(p<0.01). 따라서 양성자 자기공명분광법은 고지방식 먹이를 먹고 2주 후부터 다양한 쥐의 간 지질 변화를 검출하고 특성화하는데 유용할 것이다.

• Journal of Photoscience
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• 제9권2호
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• pp.415-417
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• 2002

Juvenile visceral steatosis (JVS) mouse is an animal model of the systemic camitine deficiency. JVS mice first develop fatty liver following cardiac hypertrophy. hyperammonemia, etc. To clarify the relationship between fatty liver and other symptoms. lipid hydroperoxides levels of peripheral oragans in JVS mice at 1 month were determined by the use of phosphine derivatives. We also report here a new method to quantitate the lipid components level in fatty liver of JVS mice.

• Pediatric Gastroenterology, Hepatology & Nutrition
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• 제24권2호
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• pp.187-196
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• 2021

Purpose: The rising prevalence of childhood obesity in the past decades has caused non-alcoholic fatty liver disease (NAFLD) to become the most common cause of pediatric chronic liver disease worldwide. This study was aimed at determining the effect of vitamin D (Vit D) on ultrasonography and laboratory indices of NAFLD and some blood biochemical indicators in children. Methods: In this interventional study liver ultrasonography was performed in 200 children with overweight and obesity. A 108 had fatty liver among which 101 were randomly divided into two groups of study (n=51) and control (n=50). The study group was treated with Vit D, 50000 U once a week whereas the control group received placebo with the same dose and package, both for 12 weeks. At the end of the intervention lab tests and ultrasound study was performed once again to evaluate the response to treatment. Results: It was found out that Vit D supplementation improved the fatty liver grade in the study group. The mean changes in hemoglobin (Hb), uric acid, highdensity lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), insulin, albumin and alanine aminotransferase (ALT) was significantly higher in the study group compared to controls (p<0.05). After the intervention and means adjustment, a significant difference was obtained in HDL-C, insulin, LDL-C and homeostasis model assessment of insulin resistance (HOMA-IR) between the two groups. Conclusion: Vit D supplementation in addition to improving the fatty liver grade in ultrasonography and increasing the blood Vit D level, increases the HDL and Hb level besides decreasing uric acid, LDL, HOMA-IR, insulin and ALT levels.

• 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.

• 대한한의학방제학회지
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• 제28권2호
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• pp.179-187
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• 2020

Objectives : This study investigated the hepatoprotective effects effects of Jageum-jung extract on alcohol-induced liver disease mice model. Methods : Alcoholic liver disease was induced by Ethanol in C57/BL6 male mice, which were fed Lieber-DeCarli liquid diet containing ethanol. Jageum-jung (100,200 and 300 mg/kg bw/day) were orally administered daily in the alcoholic fatty liver disease mice for 16 days. Results : The results indicate that Jageum-jung promotes hepatoprotective effects by significantly reducing aspartate transaminase (AST) and alanine transaminase (ALT) levels as indicators of liver damage in the serum. Furthermore, Jageum-jung decreased accumulation of triglyceride and total cholesterol, increased levels of superoxide dismutase (SOD) and glutathione (GSH) in the serum of the alcoholic fatty liver disease mice model. Additionally, it improved the serum alcohol dehydrogenase (ADH) activity. Conclusions : This study confirmed the anti-oxidative and hangover elimination effects of Jageum-jung extract, and suggests the possibility of using Jageum-jung to treat alcholic liver disease.

• Experimental and Molecular Medicine
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• 제50권12호
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• pp.2.1-2.12
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• 2018

Glucagon-like peptide-1 (GLP-1) has a broad spectrum of biological activity by regulating metabolic processes via both the direct activation of the class B family of G protein-coupled receptors and indirect nonreceptor-mediated pathways. GLP-1 receptor (GLP-1R) agonists have significant therapeutic effects on non-alcoholic fatty liver disease (NAFLD) and steatohepatitis (NASH) in animal models. However, clinical studies indicated that GLP-1 treatment had little effect on hepatic steatosis in some NAFLD patients, suggesting that GLP-1 resistance may occur in these patients. It is well-known that the gut metabolite sodium butyrate (NaB) could promote GLP-1 secretion from intestinal L cells. However, it is unclear whether NaB improves hepatic GLP-1 responsiveness in NAFLD. In the current study, we showed that the serum GLP-1 levels of NAFLD patients were similar to those of normal controls, but hepatic GLP-1R expression was significantly downregulated in NAFLD patients. Similarly, in the NAFLD mouse model, mice fed with a high-fat diet showed reduced hepatic GLP-1R expression, which was reversed by NaB treatment and accompanied by markedly alleviated liver steatosis. In addition, NaB treatment also upregulated the hepatic p-AMPK/p-ACC and insulin receptor/insulin receptor substrate-1 expression levels. Furthermore, NaB-enhanced GLP-1R expression in HepG2 cells by inhibiting histone deacetylase-2 independent of GPR43/GPR109a. These results indicate that NaB is able to prevent the progression of NAFL to NASH via promoting hepatic GLP-1R expression. NaB is a GLP-1 sensitizer and represents a potential therapeutic adjuvant to prevent NAFL progression to NASH.

• 대한한방내과학회지
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• 제33권4호
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• pp.533-542
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• 2012

Objectives : We try to compared the efficacy of six herbal medicines, Rhizoma Alismatis (RA), Fructus Crataegi (FC), Fructus Lycii (FL), Radix Curcumae (RC), Radix Salviae Miltiorrhizae (RSM), and Herba Artemisiae Scopariae (HAS), constituting KHchunggan-tang which was previously proven to be hepatoprotective on non-alcoholic fatty liver disease with combined properties of cellular steatosis, ROS production, and cytoprotection. Methods : HepG2 cells were pretreated with aqueous extracts of the six herb medicines at concentrations of 1, 10, 50 and 100 ${\mu}g/ml$ each, and treated with 0.5 mM palmitate consecutively. After 21 hrs, cell viability was assessed using MTT assay, and the percentage of cells with sub-G1 DNA content was measured using fluorescence-activated cell sorting after propidium iodide staining. Results : The first three extracts, RA, FC, and FL restored cell viability reduced by palmitate in MTT assay, and RA, FC, FL and RC inhibited palmitate-induced apoptosis in sub-G1 analysis. FL showed relatively weak potential only at tested maximal dose, and RA showed the greatest higher efficacy on this experimental cellular model of nonalcoholic fatty liver disease. Conclusions : According to this comparative experiment, Rhizoma Alismatis seems to have the most powerful potential among the six herbs constituting KHchunggan-tang, and consecutive further study seems to be required for more standardized and effective clinical application of KHchunggan-tang for treatment of non-alcoholic fatty liver disease.

• Journal of Preventive Medicine and Public Health
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• 제53권4호
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• pp.256-265
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• 2020

Objectives: We compared the associations of 3 computed tomography (CT)-based abdominal adiposity indexes with non-alcoholic fatty liver disease (NAFLD) among middle-aged Korean men and women. Methods: The participants were 1366 men and 2480 women community-dwellers aged 30-64 years. Three abdominal adiposity indexes-visceral fat area (VFA), subcutaneous fat area (SFA), and visceral-to-subcutaneous fat ratio (VSR)-were calculated from abdominal CT scans. NAFLD was determined by calculating the Liver Fat Score from comorbidities and blood tests. An NAFLD prediction model that included waist circumference (WC) as a measure of abdominal adiposity was designated as the base model, to which VFA, SFA, and VSR were added in turn. The area under the receiver operating characteristic curve (AUC), integrated discrimination improvement (IDI), and net reclassification improvement (NRI) were calculated to quantify the additional predictive value of VFA, SFA, and VSR relative to WC. Results: VFA and VSR were positively associated with NAFLD in both genders. SFA was not significantly associated with NAFLD in men, but it was negatively associated in women. When VFA, SFA, and VSR were added to the WC-based NAFLD prediction model, the AUC improved by 0.013 (p<0.001), 0.001 (p=0.434), and 0.009 (p=0.007) in men and by 0.044 (p<0.001), 0.017 (p<0.001), and 0.046 (p<0.001) in women, respectively. The IDI and NRI were increased the most by VFA in men and VSR in women. Conclusions: Using CT-based abdominal adiposity indexes in addition to WC may improve the detection of NAFLD. The best predictive indicators were VFA in men and VSR in women.