• Journal of Microbiology and Biotechnology
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• 제34권2호
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• pp.399-406
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• 2024

Lactiplantibacillus plantarum DSR330 (DSR330) has been examined for its antimicrobials production and probiotics. In this study, the hepatoprotective effects of DSR330 were examined against nonalcoholic fatty liver disease (NAFLD) in a high-fat diet (HFD)-fed C57BL/6 mouse model. To induce the development of fatty liver, a HFD was administered for five weeks, and then silymarin (positive control) or DSR330 (10⁸ or 10⁹ CFU/day) was administered along with the HFD for seven weeks. DSR330 significantly decreased body weight and altered serum and hepatic lipid profiles, including a reduction in triglyceride, total cholesterol, and low-density lipoprotein cholesterol levels compared to those in the HFD group. DSR330 significantly alleviated HFD-related hepatic injury by inducing morphological changes and reducing the levels of biomarkers, including AST, ALT, and ALP. Additionally, DSR330 alleviated the expression of SREBP-1c, ACC1, FAS, ACO, PPARα, and CPT-1 in liver cells. Insulin and leptin levels were decreased by DSR330 compared to those observed in the HFD group. However, adiponectin levels were increased, similar to those observed in the ND group. These results demonstrate that L. plantarum DSR330 inhibited HFD-induced hepatic steatosis in mice with NAFLD by modulating various signaling pathways. Hence, the use of probiotics can lead to hepatoprotective effects.

• 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.

• Journal of Ginseng Research
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• 제47권3호
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• pp.429-439
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• 2023

Background: The incidence and clinical importance of nonalcoholic fatty liver disease (NAFLD) has emerged. However, effective therapeutic strategies for NAFLD have yet to be found. Panax ginseng (P. ginseng) is a traditional herb in Eastern Asia with therapeutic effects in many chronic disorders. However, the precise effects of ginseng extract on NAFLD are currently unknown. In present study, the therapeutic effects of Rg3-enriched red ginseng extract (Rg3-RGE) on the progression of NAFLD were explored. Methods: Twelve-week-old C57BL/6 male mice were fed a chow or western diet supplemented with high sugar water solution with or without Rg3-RGE. Histopathology, immunohistochemistry, immunofluorescence, serum biochemistry, western blot analysis, and quantitative RT-PCR were used for in vivo experiment. Conditionally immortalized human glomerular endothelial cell (CiGEnC) and primary liver sinusoidal endothelial cells (LSECs) were used for in vitro experiments. Results: Eight weeks of Rg3-RGE treatment significantly attenuated the inflammatory lesions of NAFLD. Furthermore, Rg3-RGE inhibited the inflammatory infiltrate in liver parenchyma and the expression of adhesive molecules to LSECs. Moreover, the Rg3-RGE exhibited similar patterns on the in vitro assays. Conclusion: The results demonstrate that Rg3-RGE treatment ameliorates NAFLD progression by inhibiting chemotaxis activities in LSECs.

• 대한한방소아과학회지
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• 제33권2호
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• pp.12-21
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• 2019

Objectives Coptidis Rhizoma and Glycyrrhiza Uralensis are herbs that treat obesity and dampness-phlegm. The aim of this study is to investigate the efficacy of Coptidis Rhizoma and Glycyrrhiza Uralensis on lipid deposition with nonalcoholic fatty liver disease (NAFLD). Methods Male 6-week-old C57BL/6 male mice were divided into three groups: control group (Ctrl), high fat diet group (HFF), and high fat diet with Coptidis Rhizoma and Glycyrrhiza Uralensis extract administration group (CGT). Each 10 mice were allocated to each group (total of 30 mice). All mice were allowed to eat fat rich diet freely throughout the experiment. To examine the effect of Coptidis Rhizoma and Glycyrrhiza Uralensis, we observed weight changes, total cholesterol and glucose levels, lipid blot distributions, PGC-1, p-$I{\kappa}B$, and p-JNK. Results Body weights for all mice were measured and analyzed the difference between the groups. Weight gain was significantly lower in CGT group than the HFF group. Total cholesterol and glucose levels were significantly lower in CGT group. The distribution of lipid blots and positive reaction of PGC-1 were significantly lower in CGT group. The positive reaction of p-$I{\kappa}B$ in hepatic tissues was significantly lower in CGT group. The positive reaction of p-JNK in hepatic tissues was significantly lower in CGT group. Conclusions Coptidis Rhizoma and Glycyrrhiza Uralensis have the effect of improving non - alcoholic fatty liver induced insulin resistance through regulation of lipid metabolism.

• Korean Journal of Radiology
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• 제22권7호
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• pp.1077-1086
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• 2021

Objective: To investigate the diagnostic performance of quantitative ultrasound (US) parameters for the assessment of hepatic steatosis in patients with nonalcoholic fatty liver disease (NAFLD) using magnetic resonance imaging proton density fat fraction (MRI-PDFF) as the reference standard. Materials and Methods: In this single-center prospective study, 120 patients with clinically suspected NAFLD were enrolled between March 2019 and January 2020. The participants underwent US examination for radiofrequency (RF) data acquisition and chemical shift-encoded liver MRI for PDFF measurement. Using the RF data analysis, the attenuation coefficient (AC) based on tissue attenuation imaging (TAI) (AC-TAI) and scatter-distribution coefficient (SC) based on tissue scatter-distribution imaging (TSI) (SC-TSI) were measured. The correlations between the quantitative US parameters (AC and SC) and MRI-PDFF were evaluated using Pearson correlation coefficients. The diagnostic performance of AC-TAI and SC-TSI for detecting hepatic fat contents of ≥ 5% (MRI-PDFF ≥ 5%) and ≥ 10% (MRI-PDFF ≥ 10%) were assessed using receiver operating characteristic (ROC) analysis. The significant clinical or imaging factors associated with AC and SC were analyzed using linear regression analysis. Results: The participants were classified based on MRI-PDFF: < 5% (n = 38), 5-10% (n = 23), and ≥ 10% (n = 59). AC-TAI and SC-TSI were significantly correlated with MRI-PDFF (r = 0.659 and 0.727, p < 0.001 for both). For detecting hepatic fat contents of ≥ 5% and ≥ 10%, the areas under the ROC curves of AC-TAI were 0.861 (95% confidence interval [CI]: 0.786-0.918) and 0.835 (95% CI: 0.757-0.897), and those of SC-TSI were 0.964 (95% CI: 0.913-0.989) and 0.935 (95% CI: 0.875-0.972), respectively. Multivariable linear regression analysis showed that MRI-PDFF was an independent determinant of AC-TAI and SC-TSI. Conclusion: AC-TAI and SC-TSI derived from quantitative US RF data analysis yielded a good correlation with MRI-PDFF and provided good performance for detecting hepatic steatosis and assessing its severity in NAFLD.

• Clinical and Experimental Pediatrics
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• 제62권12호
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• pp.450-455
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• 2019

Background: Lipid accumulation product (LAP) is associated with the presence and severity of nonalcoholic fatty liver disease (NAFLD) in adults. Purpose: Here we evaluated the ability of LAP to predict NAFLD in obese children. Methods: Eighty obese children (38 girls; age 6-18 years) were included. Anthropometric measurements and biochemical values were obtained from the patients' medical records. LAP was calculated as [waist circumference (WC) (cm) - 58]×triglycerides (mmol/L) in girls; [WC (cm) - 65]×triglycerides (mmol/L) in boys. The minLAP and adjLAP were described (3% and 50% of WC values, respectively) and the total/high-density lipoprotein cholesterol index (TC/HDL-C) was calculated. NAFLD was observed on ultrasound, and patients were divided into 3 groups by steatosis grade (normal, grade 0; mild, grade 1; moderate-severe, grade 2-3). The area under the curve (AUC) and appropriate index cutoff points were calculated by receiver operator characteristic analysis. Results: LAP was positively correlated with puberty stage (rho=0.409; P<0.001), fasting insulin (rho= 0.507; P<0.001), homeostasis model assessment of insulin resistance (rho=0.470; P<0.001), uric acid (rho=0.522; P<0.001), and TC/HDL-C (rho=0.494; P<0.001) and negatively correlated with HDL-C (rho=-3.833; P<0.001). LAP values could be used to diagnose hepatosteatosis (AUC=0.698; P=0.002). The LAP, adjLAP, and minLAP cutoff values were 42.7 (P=0.002), 40.05 (P=0.003), and 53.47 (P= 0.08), respectively. For LAP, the differences between the normal and mild groups (P=0.035) and the normal and moderate-severe groups were statistically significant (P=0.037), whereas the difference between the mild and moderate-severe groups was not (P>0.005). There was a statistically significant difference between the normal and mild groups for adjLAP (P=0.043) but not between the other groups (P>0.005). There was no significant intergroup difference in minLAP (P>0.005). Conclusion: LAP is a powerful and easy tool to predict NAFLD in childhood. If LAP is ≥42.7, NAFLD should be suspected. This is the first study to assess LAP diagnostic accuracy for childhood obesity.

• Journal of Ginseng Research
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• 제42권4호
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• pp.419-428
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• 2018

Background: Despite the large number of studies on ginseng, pharmacological activities of ginseng seed oil (GSO) have not been established. GSO is rich in unsaturated fatty acids, mostly oleic and linoleic acids. Unsaturated fatty acids are known to exert a therapeutic effect in nonalcoholic fatty liver disease (NAFLD). In this study, we investigated the protective effect and underlying mechanisms of GSO against NAFLD using in vitro and in vivo models. Methods: In vitro lipid accumulation was induced by free fatty acid mixture in HepG2 cells and by 3 wk of high fat diet (HFD)-feeding in Sprague-Dawley rats prior to hepatocyte isolation. The effects of GSO against diet-induced hepatic steatosis were further examined in C57BL/6J mice fed a HFD for 12 wk. Results: Oil Red O staining and intracellular triglyceride levels showed marked accumulation of lipid droplets in both HepG2 cells and rat hepatocytes, and these were attenuated by GSO treatment. In HFD-fed mice, GSO improved HFD-induced dyslipidemia and hepatic insulin resistance. Increased hepatic lipid contents were observed in HFD-fed mice and it was lowered in GSO (500 mg/kg)-treated mice by 26.4% which was evident in histological analysis. Pathway analysis of hepatic global gene expression indicated that GSO increased the expression of genes associated with ${\beta}$-oxidation (Ppara, Ppargc1a, Sirt1, and Cpt1a) and decreased the expression of lipogenic genes (Srebf1 and Mlxipl), and these were confirmed with reverse transcription and quantitative polymerase-chain reaction. Conclusion: These findings suggest that GSO has a beneficial effect on NAFLD through the suppression of lipogenesis and stimulation of fatty acid degradation pathway.

• 대한본초학회지
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• 제33권5호
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• pp.1-8
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• 2018

Objectives : The aim of this study is to investigate the preventive effect of Puerariae Flos ethanol extract (PE) on methionin and choline deficient (MCD)-diet-induced Nonalcoholic fatty liver disease (NAFLD) in C57BL/6J mice. Methods : In the in vivo experiments, C57BL/6J mice were divided into 4 groups; Normal group, Control group, MCD+PE 100 group, and MCD+PE 300 group. After 4 weeks, body weight, liver weight, biochemical parameters for liver function test, histological changes, reverse transcription polymerase chain reaction (RT-PCR), and Western blot were assessed. Results : Mice lost body weight with the MCD-diet and the MCD+PE 100 group and MCD+PE 300 groups lost less than the control group, though showed no statistical significance. Liver weights were decreased by the MCD diet, but MCD+PE 300 groups were increased significantly. In the liver function test, all the values were decreased with the MCD-diet, MCD+PE 100 group and MCD+PE 300 groups were increased significance. In histological findings of the livers, MCD-diet induced severe fatty accumulation in the livers, but this fatty change was reduced in the MCD+PE 100 group and MCD+PE 300 groups was inhibited respectively. In lipid accumulation factors (such as SREBP-1c, $C/EBP{\alpha}$, PPAR-${\gamma}$), MCD+PE 100 group and MCD+PE 300 groups showed inhibitory effect on liver lipogenesis by reducing associated gene expressions caused by MCD diet. Conclusions : We were able to know that Puerariae Flos ethanol extract (PE) shown hepatoprotective effects via a decrease on the hepatic lipogenesis factors in the experimental NAFLD Models.

• Nutrition Research and Practice
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• 제9권4호
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• pp.350-357
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• 2015

BACKGROUND/OBJECTIVES: The prevalence of nonalcoholic fatty liver disease (NAFLD) has increased worldwide in parallel with overnutrition characterized by high-fat and high-carbohydrate intake. Our objective was to establish, in 16 weeks, a model of NAFLD in Wistar pathogen-free rats following four dietary types. MATERIALS/METHODS: Forty (6 weeks old) healthy Wistar male rats, weighing an average of 150 g were randomly divided into four groups of ten and assigned a diet with the same quantity (15 g/rat/day), but with different composition. The moderate-fat (MF) group was fed a moderate-fat diet (31.5% fat and 50% carbohydrates), the high-fat (HF) group was fed a fat-rich diet (51% fat), the high-sucrose (HS) group and the high-fructose (HFr) group were fed a carbohydrate-rich diet (61%). The carbohydrate contents of the HS group was composed of 60.3% sucrose while that of the HFr group was composed of 59.3% fructose. RESULTS: At week 16, the HF group had the highest percentage of cells enriched in fat (40%) and the highest weight and liver weight (P < 0.05). The HFr group showed significantly higher levels of serum triglycerides, alanine aminotransferase and adiponectin at week 16 as compared to week 1 (P < 0.05). CONCLUSIONS: The 15 g/rat/day diet composed of 51% fat or 61% carbohydrates enriched mainly in fructose may induce characteristics of NAFLD in rats.

• 생명과학회지
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• 제33권12호
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• pp.967-977
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• 2023

Rubus crataegifolius (RC)는 장미과에 속하는 전통적인 아시아 약용 식물이다. RC 열매는 항산화 작용을 통해 성인병을 예방하는 것으로 알려져 있다. 본 연구에서는 RC 열매 추출물(RCex)이 비만과 비알코올성 지방간 질환(NAFLD)에 미치는 영향을 동물 모델을 통해 평가하였다. 28마리의 수컷 C57BL/6J 마우스에 8주간 비만을 유도한 후, 추출물을 8주간 경구 투여하였다. 그룹 1은 일반 대조군으로 표준사료를 섭취하였다. 그룹 2는 HFD 대조군으로, 그룹 3에는 심바스타틴(6.5 mg/kg/일)을, 그룹 4에는 RCex (200 mg/kg)을 투여하였다. RCex투여는 실험 마우스의 체중, 지방 조직, 간 무게를 감소시켰으며, 또한 지질 대사(ALT, AST, TC, TG, LDL, HDL)를 포함한 생화학적 바이오마커를 개선하였다. AMPK의 활성화는 지방생성 유전자(LXR, SREBP-1c, FAS, ACC1)의 발현을 감소시켰으며, RCex에 의한 CPT 활성 증진 효과를 검증하였다. RCex는 또한 에너지 소비 및 신진대사와 관련된 호르몬(adiponectin 및 leptin)의 혈장 수준에도 영향을 미쳤다. 또한, RCex가 HFD로 유도된 비만 mice의 포도당 불내성을 개선했음을 확인 하였다. RCex는 AMPK의 인산화를 통해 지방산 산화 및 지방산 합성을 조절함으로써 항비만 및 항NAFLD 효과를 가짐을 처음으로 입증하였다. 이는 R. crataegifolius가 비만 및 관련 NAFLD 예방에 좋은 보충제가 될 수 있음을 시사한다.