• Yonsei Medical Journal
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• v.59 no.9
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• pp.1064-1071
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• 2018

Purpose: To explore the influence of S100 calcium binding protein A4 (S100A4) knockout (KO) on methionine-choline-deficient (MCD) diet-induced non-alcoholic fatty liver disease (NAFLD) in mice. Materials and Methods: S100A4 KO mice (n=20) and their wild-type (WT) counterparts (n=20) were randomly divided into KO/MCD, Ko/methionine-choline-sufficient (MCS), WT/MCD, and WT/MCS groups. After 8 weeks of feeding, blood lipid and liver function-related indexes were measured. HE, Oil Red O, and Masson stainings were used to observe the changes of liver histopathology. Additionally, expressions of S100A4 and proinflammatory and profibrogenic cytokines were detected by qRT-PCR and Western blot, while hepatocyte apoptosis was revealed by TUNEL staining. Results: Serum levels of aminotransferase, aspartate aminotransferase, triglyceride, and total cholesterol in mice were increased after 8-week MCD feeding, and hepatocytes performed varying balloon-like changes with increased inflammatory cell infiltration and collagen fibers; however, these effects were improved in mice of KO/MCD group. Meanwhile, total NAFLD activity scores and fibrosis were lower compared to WT+MCD group. Compared to WT/MCS group, S100A4 expression in liver tissue of WT/MCD group was enhanced. The expression of proinflammatory ($TGF-{\alpha}$, $IL-1{\beta}$, IL-6) and profibrogenic cytokines ($TGF-{\beta}1$, COL1A1, ${\alpha}-SMA$) in MCD-induced NAFLD mice were increased, as well as apoptotic index (AI). For MCD group, the expressions of proinflammatory and profibrogenic cytokines and AI in KO mice were lower than those of WT mice. Conclusion: S100A4 was detected to be upregulated in NAFLD, while S100A4 KO alleviated liver fibrosis and inflammation, in addition to inhibiting hepatocyte apoptosis.

• Annals of Occupational and Environmental Medicine
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• v.34
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• pp.33.1-33.13
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• 2022

Background: Circadian rhythm disturbance caused by shift work has adverse effects on the metabolic homeostasis of the liver. Disruption of the metabolic homeostasis of the liver causes fat accumulation in the liver. The aim of this study was to investigate the correlation between shift work and non-alcoholic fatty liver disease (NAFLD) among male workers in the steel manufacturing industry of Korea. Methods: Based on medical examination data collected in June 2020, 2,511 male subjects from one steel manufacturing company in Korea were selected in total. NAFLD was evaluated using abdominal ultrasound, which was performed by two experienced radiologists. The multinomial logistic regression analysis was performed by adjusting for age, physical activity, smoking history, alcohol consumption, body mass index, waist circumference, blood pressure, blood glucose, lipidemia, liver function test, employment duration, and hepatotoxic materials exposure status. Results: Compared to daytime workers, the odds ratio (OR) of moderate-severe NAFLD in shift workers was 1.449 (95% confidence interval [CI], 1.028-2.043). Compared to daytime workers, the ORs of moderate-severe NAFLD were significantly higher for the group that engaged in total shift work for more than 20 years (OR, 2.285; 95% CI, 1.051-4.970), the group that was not allowed to sleep during night shift work (OR, 1.463; 95% CI, 1.030-2.078), and the group that consumed food during night shift work (OR, 1.580; 95% CI, 1.093-2.284). Conclusions: There was a correlation between shift work and moderate-severe NAFLD in male steel manufacturing workers. There will be a need for more research related to the correlation of shift work with steatohepatitis and cirrhosis in the future.

• Pediatric Gastroenterology, Hepatology & Nutrition
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• v.17 no.4
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• pp.248-256
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• 2014

Purpose: Non-alcoholic fatty liver disease (NAFLD) in children has become an important public health issue because of its high prevalence and severity. Several noninvasive methods for estimating NAFLD are under investigation. We aimed to evaluate the usefulness of serum ferritin as a biomarker of severity of pediatric NAFLD patients. Methods: A total of 64 NAFLD patient were enrolled from Severance Children's Hospital from March 2010 to February 2013. Serum ferritin levels, liver related laboratory tests, liver magnetic resonance imaging (MRI) (2-dimensional [2D] proton density-fat fraction) and NAFLD severity markers were compared between obese group and overweight group. Correlation analyses were performed between serum ferritin and laboratory values including NAFLD severity markers. Results: In obese group, serum ferritin, alanine aminotransferase (ALT), total bilirubin, international normalized ratio (INR), MRI 2D proton density-fat fraction, aspartate aminotransferase (AST) to platelet ratio index (APRI) and fibrosis- 4 (FIB-4) (an index score calculated from platelet count, ALT, AST and age) were significantly higher than those of overweight group. NAFLD severity markers, APRI and FIB-4, and liver specific important laboratory values, AST, ALT, INR, cholesterol, triglyceride and low density lipoprotein show significant correlation with serum ferritin in NAFLD patients. Conclusion: Serum ferritin concentrations could be a candidate of useful severity marker in the pediatric NAFLD patients.

• Journal of Preventive Medicine and Public Health
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• v.53 no.5
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• pp.342-352
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• 2020

Objectives: The aim of this retrospective cohort study was to investigate whether non-alcoholic fatty liver disease (NAFLD) was associated with incident bone mineral density (BMD) decrease. Methods: This study included 4536 subjects with normal BMD at baseline. NAFLD was defined as the presence of fatty liver on abdominal ultrasonography without significant alcohol consumption or other causes. Decreased BMD was defined as a diagnosis of osteopenia, osteoporosis, or BMD below the expected range for the patient's age based on dual-energy X-ray absorptiometry. Cox proportional hazards models were used to estimate the hazard ratio of incident BMD decrease in subjects with or without NAFLD. Subgroup analyses were conducted according to the relevant factors. Results: Across 13 354 person-years of total follow-up, decreased BMD was observed in 606 subjects, corresponding to an incidence of 45.4 cases per 1000 person-years (median follow-up duration, 2.1 years). In the model adjusted for age and sex, the hazard ratio was 0.65 (95% confidence interval, 0.51 to 0.82), and statistical significance disappeared after adjustment for body mass index (BMI) and cardiometabolic factors. In the subgroup analyses, NAFLD was associated with a lower risk of incident BMD decrease in females even after adjustment for confounders. The direction of the effect of NAFLD on the risk of BMD decrease changed depending on BMI category and body fat percentage, although the impact was statistically insignificant. Conclusions: NAFLD had a significant protective effect on BMD in females. However, the effects may vary depending on BMI category or body fat percentage.

• Korean Journal of Plant Resources
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• v.36 no.1
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• pp.26-31
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• 2023

In this study, we investigated in vitro inhibitory activity of wild-simulated ginseng (WSG) against non-alcoholic fatty liver disease using HepG-2 cells. T0901317 treatment increased the lipid accumulation in HepG-2 cells, but WSG treatment inhibited T0901317-mediated lipid accumulation. In addition, WSG downregulated T0901317-mediated expression of SREBP-1c, ACC, FAS and SCD-1 protein. In addition, WSG increased the phosphorylation level of LKB1 and AMPK. Compound C treatment blocked WSG-mediated downregulation of SREBP-1c protein. In conclusion, WSG is considered to inhibit the accumulation of lipids and triglycerides in HepG-2 cells by inducing the activation of LKB1 and AMPK successively, thereby reducing the expression of FAS, ACC, and SCD-1 through suppression of SREBP-1c expression.

• Journal of the Korean Applied Science and Technology
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• v.38 no.2
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• pp.356-367
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• 2021

This study investigated the effect of swimming exercise on inflammation in non-alcoholic fatty liver using animal models of postmenopausal obese women. Experimental animals were divided into a sham-operate + non-swimming trained group (S/N), an ovariectomize + non-swimming trained group (O/N) and an ovariectomize + swimming trained group (O/S), and were bred while eating a high fat diet for 8 weeks. Fat accumulation in liver tissue, liver weight, and serum AST and ALT increased in O/N compared to S/N, but decreased in O/S compared to O/N. Compared to S/N, O/N decreased the gene expression of IκBα in liver tissue and increased gene expression of MCP-1, IL-6, and TNF-α. But compared to O/N, O/S increased the gene expression of IκBα in liver tissue and decreased gene expression of MCP-1, IL-6, and TNF-α. In conclusion, this study suggested that swimming exercise was effective in improving physical health by improving inflammation in non-alcoholic fatty liver in obese mice induced obesity by high fat diet after ovariectomy.

• Herbal Formula Science
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• v.24 no.2
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• pp.100-107
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• 2016

Objectives : The purpose of this study is to evaluate the anti-lipogenic effect of Sobuncheong-eum on non-alcoholic fatty liver disease in free fatty acid induced cellular model. Methods : HepG2 cells were treated with palmitate for 24h to overload intracellular triglyceride (TG) content in the presence or absence of Sobuncheong-eum extract. After palmitate treatment, Intracellular TG content was measured with TG assay kit. Several lipogenesis related markers, including AMP-activated protein kinase (AMPK), sterol regulatory element-binding transcription factor-1c (SREBP-1c), acetyl-CoA carboxylase (ACC), and fatty acid synthase (FAS), were assessed using Western-blot analyses and RT-PCR. Results : Palmitate markedly increased intracellular TG in HepG2 cells, and which were alleviated by coadministered Sobuncheong-eum extract. Sobuncheong-eum extract activated AMPK, which plays a key role in reducing hepatic lipid accumulation, and reduced lipogenic fators, SREBP-1c, ACC, and FAS. Conclusions : Taken together, it is conceivable that Sobuncheong-eum has an potential to alleviate steatosis, and which may be mediated by activating AMPK at least in part.

• 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.

• Journal of Applied Biological Chemistry
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• v.66
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• pp.159-164
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• 2023

Ferroptosis is a type of regulated cell death recently discovered, characterized by the accumulation of iron-dependent lipid peroxides in the cell membrane, and it involves a complex network of signaling pathways, including iron metabolism, lipid peroxidation, and redox regulation. The dysregulation of these pathways can lead to the induction of ferroptosis and the development of liver diseases, such as alcoholic liver disease, non-alcoholic fatty liver disease, viral hepatitis, and liver cancer. Studies have demonstrated that targeting key molecules involved in iron metabolism, lipid peroxidation, and redox regulation can reduce liver injury and improve liver function in different liver diseases by inhibiting ferroptosis. Thus, modulation of ferroptosis presents a promising therapeutic target for treating liver diseases. However, further research is required to gain a more comprehensive understanding of the mechanisms underlying the role of ferroptosis in liver diseases and to develop more effective and targeted treatments.

• Journal of Korea Association of Health Promotion
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• v.3 no.2
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• pp.121-136
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• 2005

Background/Aims The liver funtion tests(LFTs), such as aspartate aminotransferase(AST), alanine amino-transferase(ALT), r -glutamyl transferase( r -GT), have been widely used for screening tests but their low positive predictive value can cause many false positive results. To evaluate the clinical usefulness of these tests, we analyzed serial LFT results of single factory workers and compared the risk factor's in groups divided by the serial LFT results. Methods From June 2001 to October 2001, 1223 consecutive healthy workers in a single factory were enrolled and questionnaire, LFT and liver ultrasonography were performed. Previous LFT results were collected from Annual Health Examination Survey. According to the abnormalities in serial LFT, participants were classified into three groups (abnormal-in-both, alternating normal-in-both) and the risk factors were compared among these groups using multiple logistic regression Results The prevalence of LFT abnormality in a single test was 16.8% but, in serial LFT, only 5% of participants showed consistent abnormality. The risk factors for abnormal-in-both group, compared with alternating group, were liver ultrasonography abnormality such as fatty liver(odds ratio, 2.2; p=0.026) and heavy alcohol intake (more than 210g/week) (odds ratio, 7.2;P=0.064). HBsAg was not significant risk factor for any of the three groups. ConclusionIn factory workers with serial LFT abnormality, alcoholic liver disease could be the principal cause of abnormal LFT. Even if HBsAg were positive in patients with abnormal LFT, there is a possibility of another causes for LFT abnormalities such as alcoholic liver disease and nonalcoholic steatosis or steatohepatitis