• BMB Reports
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• v.53 no.6
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• pp.317-322
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• 2020

Non-alcoholic fatty liver disease (NAFLD) is one of the most common liver diseases. NAFLD can further progress to irreversible liver failure such as non-alcoholic steatohepatitis (NASH) fibrosis and cirrhosis. However, specific regulator of NASH-fibrosis has yet to be established. Here, we found that glutathione peroxidase 7 (GPx7) was markedly expressed in NASH fibrosis. Although GPx7 is an antioxidant enzyme protecting other organs, whether GPx7 plays a role in NASH fibrosis has yet to be studied. We found that knockdown of GPx7 in transforming growth factor-β (TGF-β) and free fatty acids (FFA)-treated LX-2 cells elevated the expression of pro-fibrotic and pro-inflammatory genes and collagen synthesis. Consistently, GPx7 overexpression in LX-2 cells led to the suppression of ROS production and reduced the expression of pro-fibrotic and pro-inflammatory genes. Further, NASH fibrosis induced by choline-deficient amino acid defined, high fat diet (CDAHFD) feeding was significantly accelerated by knockdown of GPx7, as evidenced by up-regulated liver fibrosis and inflammation compared with CDAHFD control mice. Collectively, these results suggest that GPx7 might be a novel therapeutic target to prevent the progression and development of NAFLD.

• Pediatric Gastroenterology, Hepatology & Nutrition
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• v.15 no.2
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• pp.74-78
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• 2012

With a markedly increased prevalence of obesity, non-alcoholic fatty liver disease (NAFLD) now becomes the most common cause of chronic liver disease in both adults and children. The etiology and pathogenesis of NAFLD are multifactorial and remain incompletely understood. According to the "two-hit" theory, inflammatory cytokines and adipokines are activated by oxidative stress and they are involved in insulin resistance, necroinflammatory steatohepatitis and fibrosis. This review discusses the latest updates on the role of some of important inflammatory adipokines and cytokines in the pathogenesis of NAFLD with an emphasis on their potential therapeutic implications.

• 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.

• Pediatric Gastroenterology, Hepatology & Nutrition
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• v.18 no.3
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• pp.168-174
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• 2015

Purpose: Recent studies have suggested that decreased serum potassium level may contribute to various metabolic disorders in adult patients including nonalcoholic fatty liver disease (NAFLD). We aimed to study the correlation between serum potassium levels and the histologic severity of NAFLD in children. Methods: Pediatric patients with biopsy-proven NAFLD were included in this study. Demographic, clinical, and histopathological data were obtained. Multivariable logistic regression analysis was used to assess whether potassium levels are associated with the presence of nonalcoholic steatohepatitis (NASH) or fibrosis after adjusting for possible confounders. A p-value <0.05 was considered statistically significant. Results: Among 125 biopsies, 49.6% (62) had evidence of NASH while 66.4% (83) had some degree of fibrosis (stage 1-3). Mean serum potassium was significantly lower in NASH group as compared to non-NASH group ($4.4{\pm}0.42mmoL/L$ vs. $4.8{\pm}0.21$, p<0.001). Higher potassium level had negative correlation with presence of steatosis, ballooning, lobular inflammation, fibrosis and NAFLD activity score (p<0.05). On multivariable analysis and after adjusting for the metabolic syndrome and insulin resistance, higher potassium level was significantly associated with lower likelihood of having a histological diagnosis of NASH on biopsy (odds ratio [OR], 0.12; 95% confidence interval [95% CI], 0.05-0.28; p<0.001). Similarly, the likelihood of having fibrosis decreases by 76% for every 0.5 mmoL/L increase in potassium (OR, 0.24; 95% CI, 0.11-0.54; p<0.001). Conclusion: Our study shows an inverse relationship between serum potassium levels and the presence of aggressive disease (NASH and fibrosis) in children with NAFLD.

• Journal of Korean Medicine for Obesity Research
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• v.22 no.2
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• pp.167-172
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• 2022

Obesity is known as the most common risk factor for non-alcoholic fatty liver disease. Weight loss is needed to prevent liver function damage from progressing to non-alcoholic hepatosteatosis (NASH) and NASH-related liver cirrhosis. The purpose of this study was to observe the recovery of liver function in obese patients with liver dysfunction through traditional Korean obesity treatment. Body weight, liver function levels and renal function levels were examined by prescribing traditional Korean medicine in obese patients with mild elevation of liver function test. Blood tests were conducted at intervals of one month, and it was observed that liver function recovered to the normal range in three patients.

• Journal of Physiology & Pathology in Korean Medicine
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• v.33 no.5
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• pp.288-294
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• 2019

Gardenia jasminoides is an herbal medicine that treats obesity and dampness-phlegm. This study aimed to investigate the efficacy of Gardenia jasminoides on insulin resistance induced by Non-alcoholic fatty liver disease (NAFLD). 8-week-old C57BL/6 male mice were divided into three groups: control group (Ctrl), high-fat diet group (HFF), and high fat diet with Gardenia jasminoides extract administration group (GJT). Each 10 mice was allocated to each group (a total of 30 mice). All mice were allowed to eat fat-rich diet freely throughout the experiment. To examine the effect of Gardenia jasminoides, we observed weight changes, lipid blot distributions, PPAR-${\gamma}$, p-IkB, p-JNK in liver tissue, total cholesterol, and glucose levels in serum. Comparing of body weight measurements between 3 groups, in the GJT group, weight gain was significantly suppressed compared to the HFF group. The distribution of lipid blots and positive reaction of PPAR-${\gamma}$ were significantly lower in GJT group. The expression levels of p-$I{\kappa}B$ and p-JNK that plays critical roles in the development of insulin resistance were significantly decreased by GJ treatment. Total cholesterol and glucose levels in serum were also significantly lower in GJT group. Gardenia jasminoides has the effect of improving non - alcoholic fatty liver induced insulin resistance through the regulation of lipid metabolism.

• 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 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.

• 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.

• 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.