• Journal of Biomedical Engineering Research
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• v.43 no.1
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• pp.1-10
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• 2022

Non-alcoholic fatty liver disease(NAFLD) is excessive hepatic lipid accumulation mainly caused by obesity. This study aimed to evaluate whether micro-current stimulation(MCS) could modulate lipid metabolism regarding the Sirt1/AMPK pathway, fatty acid β-oxidation pathway, and lipolysis and lipogenesis-related factors in FL83B cells. For the NAFLD cell model, FL83B cells were treated with oleic acid for lipid accumulation. MCS were stimulated for 1 hr and used frequency 10 Hz, duty cycle 50%, and biphasic rectangular current pulse. The intensity of MCS was divided into 50, 100, 200, and 400 ㎂. Through the results of Oil red O staining, it was confirmed that MCSs with the intensity of 200 ㎂ and 400 ㎂ significantly reduced the degree of lipid droplet formation. Thus, these MCS intensities were applied to western blot analysis. Western blot analysis was performed to analyze the effects of MCS on lipid metabolism. MCS with the intensity of 400 ㎂ showed that significantly activated the Sirt1/AMPK pathway, a key pathway for regulating lipid metabolism in hepatocytes, and fatty acid β-oxidation-related transcription factors. Moreover, it activated the lipolysis pathway and suppressed lipogenesis-related transcription factors such as SREBP-1c, FAS, and PPARγ. In the case of MCS with the intensity of 200 ㎂, only PGC1α and SREBP-1c showed significant differences compared to cells treated only with oleic acid. Taken together, these results suggested that MCS with the intensity of 400 ㎂ could alleviate hepatic lipid accumulation by modulating lipid metabolism in hepatocytes.

• Clinical and Molecular Hepatology
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• v.24 no.4
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• pp.392-401
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• 2018

Background/Aims: Leptin is associated with metabolic disorders, which predispose one to non-alcoholic fatty liver disease (NAFLD). The role of leptin in NAFLD pathogenesis is not fully understood. We aim to investigate the association between serum leptin level and severity of NAFLD using U.S. nationally representative data. Methods: Data were obtained from the United States Third National Health and Nutrition Examination Survey. NAFLD was defined by ultrasound detection and severity of hepatic steatosis in the absence of other liver diseases. The severity of hepatic fibrosis was determined by NAFLD fibrosis score (NFS). We used multivariate survey-weighted generalized logistic regression to evaluate the association between leptin level and the degree of NAFLD. We also performed subgroup analyses by body mass index (lean vs. classic NAFLD). Results: Among 4,571 people, 1,610 (35%) had NAFLD. By ultrasound findings, there were 621 people with mild, 664 with moderate, and 325 with severe steatosis. There were 885 people with low NFS (<-1.455, no significant fibrosis), 596 with intermediate NFS, and 129 with high NFS (>0.676, advanced fibrosis). Leptin levels for normal, mild, moderate and severe steatosis were $10.7{\pm}0.3ng/mL$, $12.1{\pm}0.7ng/mL$, $15.6{\pm}0.8ng/mL$, $16{\pm}1.0ng/mL$, respectively (trend P-value<0.001). Leptin levels for low, intermediate, and high NFS were $11.8{\pm}0.5ng/mL$, $15.6{\pm}0.8ng/mL$, $28.5{\pm}3.5ng/mL$, respectively (trend P-value<0.001). This association remained significant even after adjusting for known demographic and metabolic risk factors. In the subgroup analysis, this association was only prominent in classic NAFLD, but not in lean NAFLD. Conclusions: Serum leptin level is associated with the severity of NAFLD, especially in classic NAFLD patients.

• 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.

• The Journal of Internal Korean Medicine
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• v.33 no.4
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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.

• The Journal of Internal Korean Medicine
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• v.35 no.2
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• pp.175-183
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• 2014

Objectives : We tried to uncover the anti-lipogenic effect and underlying mechanism of Laminaria japonica on an experimental cellular model of non-alcoholic fatty liver disease. Methods : Ethanol extract of Laminaria japonica (LJ) was prepared. Intracellular lipid content of palmitate-treated HepG2 cells was evaluated with or without LJ treatment. We measured the effects of LJ on liver X receptor ${\alpha}$ ($LXR{\alpha}$) and sterol regulatory element-binding transcription factor-1c (SREBP-1c) expression, transcription level of lipogenic genes, including acetyl-CoA carboxylase (ACC), fatty acid synthase (FAS), stearoyl-CoA desaturase-1 (SCD-1), and nuclear factor erythroid 2-related factor 2 (Nrf2) activation in HepG2 cells. Results : LJ markedly attenuated palmitate-induced intracellular lipid accumulation in HepG2 cells. LJ suppressed $LXR{\alpha}$-dependent SREBP-1c activation, and SREBP-1c mediated induction of ACC, FAS, and SCD-1. Furthermore, LJ activated Nrf2, which plays an important cytoprotective role in non-alcoholic fatty liver disease. Conclusions : Our study suggests that LJ has the potential to alleviate hepatic lipid accumulation, and this effect was mediated by inhibiting the $LXR{\alpha}$-SREBP-1c pathway that leads to hepatic steatosis. In addition, the anti-lipogenic potential may, at least in part, be associated with activation of Nrf2.

• Nutrition Research and Practice
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• v.8 no.2
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• pp.172-176
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• 2014

BACKGROUND/OBJECTIVES: Non-alcoholic fatty liver disease (NAFLD) is becoming an important public health problem as metabolic syndrome and type 2 diabetes have become epidemic. In this study we investigated the protective effect of Cordyceps militaris (C. militaris) against NAFLD in an obese mouse model. MATERIALS/METHODS: Four-week-old male ob/ob mice were fed an AIN-93G diet or a diet containing 1% C. militaris water extract for 10 weeks after 1 week of adaptation. Serum glucose, insulin, free fatty acid (FFA), alanine transaminase (ALT), and proinflammatory cytokines were measured. Hepatic levels of lipids, glutathione (GSH), and lipid peroxide were determined. RESULTS: Consumption of C. militaris significantly decreased serum glucose, as well as homeostasis model assessment for insulin resistance (HOMA-IR), in ob/ob mice. In addition to lowering serum FFA levels, C. militaris also significantly decreased hepatic total lipids and triglyceride contents. Serum ALT activities and tumor necrosis factor-${\alpha}$ (TNF-${\alpha}$) and interleukin-6 (IL-6) levels were reduced by C. militaris. Consumption of C. militaris increased hepatic GSH and reduced lipid peroxide levels. CONCLUSIONS: These results indicate that C. militaris can exert protective effects against development of NAFLD, partly by reducing inflammatory cytokines and improving hepatic antioxidant status in ob/ob mice.

• The Journal of Internal Korean Medicine
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• v.43 no.4
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• pp.680-719
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• 2022

Objectives: The aim of this study was to investigate the trends in research on non-alcoholic fatty liver disease (NAFLD) using Korean traditional medicine. Methods: This review included studies related to the treatment of NAFLD, irrespective of the year of publication. The search terms were "nonalcoholic fatty liver disease", "non-alcoholic fatty liver", "nonalcoholic hepatitis", "herb", "herbal medicine", "acupuncture", and "traditional medicine". The studies were analyzed according to the type of research. Results: After screening, 179 studies were selected from the 592 identified by the search. The types of studies were 151 in vivo or in vitro studies, 5 randomized controlled trials, 12 case reports, 2 unspecified clinical studies, 8 review articles, and 1 article that was difficult to classify. Conclusion: Analysis of the trends in Korean traditional medicine treatment by reviewing the studies on NAFLD revealed a focus on experimental studies rather than clinical studies. Therefore, multifaceted and well-designed studies are needed.

• The Journal of Pediatrics of Korean Medicine
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• v.34 no.4
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• pp.11-21
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• 2020

Objectives This study aimed to investigate the efficacy of Ephedra sinica (E. sinica), Panax ginseng (P. ginseng), and Alisma orientale (A. orientale) Extract (MIT) on insulin resistance induced by Non-alcoholic fatty liver disease (NAFLD). Methods C57BL /6 male mice (8-week-old, 20 g) were divided into four groups: control group (Ctrl), high-fat diet group (HFDF), high fat diet with metformin administration group (METT), and high fat diet with MIT administration group (MITT). Each 10 mice were allocated to each group (a total of 40 mice). All mice were allowed to eat fat-rich diet freely throughout the experiment. To examine the effect of MIT, we observed Cannabinoid receptor type 1 (CB1), Cannabinoid receptor type 2 (CB2), G protein-coupled receptor 55 (GPR55), and Transforming growth factor-β (TGF-β). Results In the MITT group, positive reactions of the CB1, CB2, and GPR55 were significantly was significantly suppressed compared to the HFDF group. The positive reactions of the CD36 and TGF-β in the liver tissue were significantly suppressed in MITT. Conclusions MIT has the effect of improving NAFLD induced insulin resistance through the regulation of the lipid metabolism.

• Clinical Nutrition Research
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• v.12 no.1
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• pp.29-39
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• 2023

Previous studies have frequently reviewed how different macronutrients affect liver health. Still, no study centered around protein intake and the non-alcoholic fatty liver disease (NAFLD) risk relationship. This study aimed to examine the association between the consumption of total and different sources of protein and NAFLD risk. We allocated 243 eligible subjects to the case and control groups, including 121 incidence cases of NAFLD, and 122 healthy controls. Two groups were matched in age, body mass index, and sex. We evaluated the usual food intake of participants using FFQ. Binary logistic regression was conducted to estimate the risk of NAFLD in relation to different sources of protein intake. The age of participants was 42.7 years on average, and 53.1% were male. We found Higher intake of protein in total (odds ratio [OR], 0.24; 95% confidence interval [CI], 0.11-0.52) was significantly associated with a lower risk of NAFLD, despite adjusting for multiple confounders. in detail, higher tendency to the vegetables (OR, 0.28; 95% CI, 0.13-0.59), grains (OR, 0.24; 95% CI, 0.11-0.52), and nuts (OR, 0.25; 95% CI, 0.12-0.52) as the main sources of protein, were remarkably correlated with lower NAFLD risk. In contrary, increased intake of meat protein (OR, 3.15; 95% CI, 1.46-6.81) was positively associated with a higher risk. Totally, more calorie intake from proteins was inversely associated with lower NAFLD risk. This was more likely when the protein sources were selected less from meats and more from plants. Accordingly, increasing the consumption of proteins, particularly from plants, may be a good recommendation to manage and prevent NAFLD.

• Journal of Life Science
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• v.30 no.5
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• pp.434-442
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• 2020

In this study, Tenebrio molitor (brown mealworm) larvae powder was fermented with Saccharomyces cerevisiae M1 (KACC 93023). The fermented and non-fermented powders were subsequently administered to rats with induced non-alcoholic fatty liver disease to compare the degree of improvement. The rats exhibited abnormal lipid metabolism due to orotic acid, and the group that were fed the fermented larvae powder showed similar weight to normal rats. AST, ALT, ALP, and LDH activities, all known indicators of liver health, and various other lipid-related indicators appeared positive, suggesting improvement. The lipid peroxide and glutathione content in the liver tissue and serum were similar to or better than those of the normal group. Finally, morphological observations of liver tissue using H&E and oil red O stainings revealed that the fermented powder group showed markedly reduced fat along with normal hepatocyte shape and arrangement. To summarize, it was confirmed that dietary brown mealworm larvae improve non-alcoholic fatty liver function, and, when fermented with yeast, most indicators showed positive improvements to almost normal levels. As such, the fermented powder can be considered to improve non-alcoholic fatty liver, suggesting that it may be used as a material for various products in the future.