• Journal of Nutrition and Health
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• v.47 no.5
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• pp.330-341
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• 2014

Purpose: The purpose of this study was to evaluate dietary habits, food intakes, nutrient intakes, and diet quality of non-alcoholic fatty liver disease in a health screening and promotion center. Methods: The total number of study subjects was 10,111 adults, where 3087 subjects (30.5%) were diagnosed as NAFLD. The dietary intakes were obtained using a food frequency questionnaire. They were then compared with the dietary reference intakes could be used in the future for development of diet and nutrition guidelines s (KDRIs). Results: Mean age of subjects in the normal group was $52.9{\pm}10.3yrs$ and body mass index (BMI) was $22.4{\pm}2.6kg/m^2$, and those of the NAFLD group were $55.1{\pm}9.2yrs$ and $25.4{\pm}2.9kg/m^2$. BMI, blood pressure of the NAFLD group were significantly higher than those of the normal group. The rates of skipping breakfast, overeating, and eating out were significantly could be used in the future for development of diet and nutrition guidelines er in the NAFLD group (p < 0.05, p < 0.000, p < 0.000 respectively). The speed of eating was fast in the NAFLD group (p < 0.000). The NAFLD group consumed significantly higher amounts of grains, meats, fish, seaweeds, kimchies, sugars, sweets, coffee, teas, and oils compared to the normal group (p < 0.05). Meanwhile, intakes of starch products, fruits, milk, and milk products were significantly lower in the NAFLD group compared with those of the normal group (p < 0.05). Riboflavin, calcium, and dietary fiber nutrient adequacy ratio (NAR) of the NAFLD group were significantly lower than those of the normal group. The Korean's dietary diversity score (KDDS) of the NAFLD group was lower than that of the normal group. Conclusion: In conclusion, we suggest that diet guidelines, such as increasing the intake of calcium and dietary fiber, reducing the intake of energy, fat, and simple carbohydrates, are necessary to improvement of NAFLD. The results could be used in the future for development of diet and nutrition guidelines for NAFLD.

• Pediatric Gastroenterology, Hepatology & Nutrition
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• v.10 no.2
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• pp.179-184
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• 2007

Purpose: Obesity has recently emerged as a significant health problem in the pediatric population, and the prevalence of non-alcoholic fatty liver disease is increasing in tandem with a significant rise in childhood obesity. Therefore, this study was conducted to clarify the risk factors of non-alcoholic steatohepatitis in obese children. Methods: We enrolled 84 obese children who visited the pediatric obesity clinic at Yeung-Nam university hospital. The patients were divided into two groups based on their alanine aminotransferase (ALT) level (separated at 40 IU/L), and the mean of ages, total cholesterol levels, HDL-cholesterol levels, LDL-cholesterol levels, triglyceride (TG) levels, as well as the mean obesity index, and body fat percentage of the two groups were then compared. Results: When the mean of ages ($10.5{\pm}1.6$ vs. $10.7{\pm}2.0$ years), total cholesterol levels ($183.0{\pm}29.1$ vs. $183.7{\pm}31.3$ mg/dL), HDL-cholesterol levels ($53.0{\pm}10.2$ vs. $55.7{\pm}13.0$ mg/dL), LDL-cholesterol levels ($113.4{\pm}30.2$ vs. $113.0{\pm}30.0$ mg/dL), triglyceride levels ($99.4{\pm}62.9$ vs. $114.2{\pm}47.3$ mg/dL), obesity indexes ($44.7{\pm}12.2$ vs. $47.9{\pm}15.1%$), and body fat percentages ($32.7{\pm}5.0$ vs. $34.0{\pm}4.8%$) of group 1 (ALT${\leq}$40 IU/L) were compared with those of group 2 (ALT${\geq}$41 IU/L), no significant differences were observed (p>0.05). However, hypertriglyceridemia (TG${\geq}$110 mg/dL) was more frequent in group 2 than in group 1 (p=0.023). Conclusion: TG may be an important risk factor in non-alcoholic steatohepatitis and further study regarding the risk factors in non-alcoholic steatohepatitis is required.

• Journal of Life Science
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• v.29 no.9
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• pp.964-971
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• 2019

Hepatic lipid accumulation and insulin resistance increases in patients with non-alcoholic fatty liver disease. Piperine is a major compound found in black pepper (Piper nigrum) and long pepper (P. longum). Piperine has been used in fine chemical for its anti-cancer, anti-obesity, anti-diabetic, anti-inflammatory and anti-oxidant properties. However, the signaling-based mechanism of piperine and its role as an inhibitor of lipogenesis and insulin resistance in human hepatocyte cells remains ill-defined. In the present study, we explored the effects of piperine on lipid accumulation and insulin resistance, and explored the potential underlying molecular mechanisms in palmitate-treated HepG2 cells. Piperine treatment resulted in a significant reduction of triglyceride content. Furthermore, piperine treatment decreased palmitate-treated intracellular lipid deposition by inhibiting the lipogenic target genes, sterol-regulatory-element-binding protein 1c (SREBP-1c) and fatty acid synthase (FAS); whereas the expression of carnitine palmitoyl transferase (CPT-1) and phosphorylation of acetyl coenzyme A carboxylase (ACC) gene involved in fatty acid oxidation was increased. Moreover, piperine also inhibited the phosphorylation of insulin receptor substrate (IRS)-1 (Ser307). Piperine treatment modulated palmitate-treated lipid accumulation and insulin resistance in HepG2 cells with concomitant reduction of lipogenic target genes, such as SREBP-1 and FAS, and induction of CPT-1-ACC and phosphorylation of IRS-1 (Tyr632)-Akt pathways. Therefore, piperine represents a promising treatment for the prevention of lipid accumulation and insulin resistance.

• Journal of Life Science
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• v.30 no.7
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• pp.640-650
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• 2020

Fibroblast growth factor 21 (FGF21) is an atypical member of the FGF protein family which is highly synthesized in the liver, pancreas, and adipose tissue. Depending on the expression tissue, FGF21 uses endo- or paracrine features to regulate several metabolic pathways including glucose metabolism and energy homeostasis. Different physiologically stressful conditions such as starvation, a ketogenic diet, extreme cold, and mitochondrial dysfunction are known to induce FGF21 synthesis in various tissues to exert either adaptive or defensive mechanisms. More specifically, peroxisome proliferator-activated receptor gamma and peroxisome proliferator-activated receptor alpha control FGF21 expression in adipose tissue and liver, respectively. In addition, the pharmacologic administration of FGF21 has been reported to decrease the body weight and improve the insulin sensitivity and lipoprotein profiles of obese mice and type 2 diabetes patients meaning that FGF21 has attracted huge interest as a therapeutic agent for type 2 diabetes, obesity, and non-alcoholic fatty liver disease. However, understanding FGF21 remains complicated due to the paradoxical condition of its tissue-dependent expression. For example, nutrient deprivation largely increases hepatic FGF21 levels whereas adipose tissue-derived FGF21 is increased under feeding condition. This review discusses the issues of interest that have arisen from existing publications, including the tissue-specific function of FGF21 and its action mechanism. We also summarize the current stage of a clinical trial using several FGF21 analogs.

• BMB Reports
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• v.55 no.12
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• pp.609-614
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• 2022

Mutation of the gene for adenomatous polyposis coli (APC), as seen in Apc^Min/+ mice, leads to intestinal adenomas and carcinomas via stabilization of β-catenin. Transmembrane 4 L six family member 5 (TM4SF5) is involved in the development of non-alcoholic fatty liver disease, fibrosis, and cancer. However, the functional linkage between TM4SF5 and APC or β-catenin has not been investigated for pathological outcomes. After interbreeding Apc^Min/+ with TM4SF5-overexpressing transgenic (Tg^TM4SF5) mice, we explored pathological outcomes in the intestines and livers of the offspring. The intestines of 26-week-old dual-transgenic mice (Apc^Min/+:Tg^TM4SF5) had intramucosal adenocarcinomas beyond the single-crypt adenomas in Apc^Min/+ mice. Additional TM4SF5 overexpression increased the stabilization of β-catenin via reduced glycogen synthase kinase 3β (GSK3β) phosphorylation on Ser9. Additionally, the livers of the dualtransgenic mice showed distinct sinusoidal dilatation and features of hepatic portal hypertension associated with fibrosis, more than did the relatively normal livers in Apc^Min/+ mice. Interestingly, TM4SF5 overexpression in the liver was positively linked to increased GSK3β phosphorylation (opposite to that seen in the colon), β-catenin level, and extracellular matrix (ECM) protein expression, indicating fibrotic phenotypes. Consistent with these results, 78-week-old Tg^TM4SF5 mice similarly had sinusoidal dilatation, immune cell infiltration, and fibrosis. Altogether, systemic overexpression of TM4SF5 aggravates pathological abnormalities in both the colon and the liver.

• Journal of health informatics and statistics
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• v.43 no.4
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• pp.329-335
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• 2018

Objectives: In recent years, there has been an increased need for a way to extract desired information from multiple medical literatures at once. This study was conducted to confirm the usefulness of unstructured data analysis using previously published medical literatures to search for new indications. Methods: The new indications were searched through text mining, network analysis, and topic modeling analysis using 5,057 articles of atorvastatin, a treatment for hyperlipidemia, from 1990 to 2017. Results: The extracted keywords was 273. In the frequency of text mining and network analysis, the existing indications of atorvastatin were extracted in top level. The novel indications by Term Frequency-Inverse Document Frequency (TF-IDF) were atrial fibrillation, heart failure, breast cancer, rheumatoid arthritis, combined hyperlipidemia, arrhythmias, multiple sclerosis, non-alcoholic fatty liver disease, contrast-induced acute kidney injury and prostate cancer. Conclusions: Unstructured data analysis for discovering new indications from massive medical literature is expected to be used in drug repositioning industries.

• The Journal of Internal Korean Medicine
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• v.43 no.4
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• pp.606-624
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• 2022

Objective: The aim of this study was to compare the effects of different doses of Geumnyeonyijin-tang (GNYJT) water extracts with those of metformin (250 mg/kg) in mild diabetic-obese mice. Methods and Results: The 48 mice were divided into 1 normal pellet diet (NFD) group and 5 high-fat diet (HFD) groups. At the end of 12 weeks of oral administration of metformin (250 mg/kg) or GNYJT water extracts (400, 200, or100 mg/kg), the effects were evaluated. The HFD control mice showed noticeable increases in body weight, adipose tissue density, fat pad weight of the periovarian and abdominal wall, and insulin, blood glucose, and HbA1c levels, with decreases in serum HDL levels. Increases in the periovarian and dorsal abdominal fat pad, regions of steatohepatitis, adipocyte hypertrophy, and hepatocyte hypertrophy were also discovered. The HFD group showed a decline in glucose levels and elevation of hepatic gluconeogenesis, suggesting an HFD-induced AMPK downregulation related to glucose dysregulation, as well as lipid metabolism related to obese insulin-resistant type II diabetes, dyslipidemia, and oxidative stress related diabetic hepatopathy (non-alcoholic fatty liver disease, NAFLD). Conclusion: Assessment of the key parameters for inhibition of diabetes and related complications in HFD-fed diabetic-obese mice demonstrated that GNYJT water extracts have favorable ameliorating effects. The effect of GNYJT was manifested through the stimulation of AMPK upregulation of related hepatic glucose enzyme activities and expression of lipid metabolism-related genes. Therefore, appropriate oral dosages of GNYJT could be promising as a new preventive candidate for controlling diabetes and related complications. Further screening of biologically active compounds, elucidation of detailed mechanisms, and more animal studies are warranted.

• Journal of Life Science
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• v.18 no.8
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• pp.1053-1058
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• 2008

Glutathione is a well known chemotherapeutic agent for liver disease and is a popular nutritional supplement in the United States. Previous our studies reported the suppressive effects of glutathione-enriched Saccharomyces cerevisiae FF-8 strain (FF-8GY) on carbon tetrachloride- and alcohol-induced hepatotoxicity. The primary objective of this study was to investigate the comparative effects of FF-8GY and commercially available glutathione-enriched yeast extract (GYE) against the oxidative stress in alcohol-induced fatty liver of rats. The lipid peroxidative index (thiobarbituric acid-reactive substances, TBARS) and antioxidant status (reduced glutathione level) were used to monitor those protective roles of FF-8GY or GYE treatment. When the rat was treated alcohol, the TBARS levels in the whole liver and the subfractions of microsomal and mitochondria were significantly increased but these were significantly decreased by FF-8GY treatment and tended to be lowered by GYE treatment. The concentration of hepatic glutathione is known to be closely associated with antioxidant system and this was slightly deplete in the alcohol-induced rats, but this was recovered by treating with FF-8GY. However, the glutathione concentration was more significantly decreased in the GYE supplementation in alcohol feeding rats. Alcohol treatment also negatively affected the serum total protein and albumin, but these were significantly increased near normal levels in FF-8GY coadministered rats. These results suggest that glutathione-enriched Saccharomyces cerevisiae FF-8 strain may have positively mediate the alcohol-induced oxidative stress, and this effect was more pronounced in FF-8GY compared to GYE.

• Journal of Animal Science and Technology
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• v.63 no.4
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• pp.934-953
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• 2021

Ciglitazone is a member of the thiazolidinedione family, and specifically binds to peroxisome proliferator-activated receptor-γ (PPARγ), thereby promoting adipocyte differentiation. We hypothesized that ciglitazone as a PPARγ ligand in the absence of an adipocyte differentiation cocktail would increase adiponectin and adipogenic gene expression in bovine satellite cells (BSC). Muscle-derived BSCs were isolated from six, 18-month-old Yanbian Yellow Cattle. The BSC were cultured for 96 h in differentiation medium containing 5 µM ciglitazone (CL), 10 µM ciglitazone (CM), or 20 µM ciglitazone (CH). Control (CON) BSC were cultured only in a differentiation medium (containing 2% horse serum). The presence of myogenin, desmin, and paired box 7 (Pax7) proteins was confirmed in the BSC by immunofluorescence staining. The CL, CM, and CH treatments produced higher concentrations of triacylglycerol and lipid droplet accumulation in myotubes than those of the CON treatment. Ciglitazone treatments significantly increased the relative expression of PPARγ, CCAAT/enhancer-binding protein alpha (C/EBPα), C/EBPβ, fatty acid synthase, stearoyl-CoA desaturase, and perilipin 2. Ciglitazone treatments increased gene expression of Pax3 and Pax7 and decreased expression of myogenic differentiation-1, myogenin, myogenic regulatory factor-5, and myogenin-4 (p < 0.01). Adiponectin concentration caused by ciglitazone treatments was significantly greater than CON (p < 0.01). RNA sequencing showed that 281 differentially expressed genes (DEGs) were found in the treatments of ciglitazone. DEGs gene ontology (GO) analysis showed that the top 10 GO enrichment significantly changed the biological processes such as protein trimerization, negative regulation of cell proliferation, adipocytes differentiation, and cellular response to external stimulus. Kyoto Encyclopedia of Genes and Genomes pathway analysis showed that DEGs were involved in the p53 signaling pathway, PPAR signaling pathway, biosynthesis of amino acids, tumor necrosis factor signaling pathway, non-alcoholic fatty liver disease, PI3K-Akt signaling pathway, and Wnt signaling pathway. These results indicate that ciglitazone acts as PPARγ agonist, effectively increases the adiponectin concentration and adipogenic gene expression, and stimulates the conversion of BSC to adipocyte-like cells in the absence of adipocyte differentiation cocktail.

• Journal of Nutrition and Health
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• v.46 no.4
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• pp.307-314
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• 2013

Resveratrol (RSV) exerts several beneficial effects on metabolism and metaflammation-related diseases, including diabetes and non-alcoholic fatty liver disease (NAFLD). The purpose of this study is to investigate whether RSV affects pathophysiology of diabetes and NAFLD as well as hepatic autophagy in a rodent model of diet induced obesity (DIO). DIO was induced in a subset of C57BL/6J mice fed a high fat (HF, 45% kcal fat) diet. After six weeks of HF diet treatment, RSV (8 mg/kg/day) was administered via an osmotic pump for a period of four weeks. Therefore, the experimental groups were as follows: 1) lean control (CON), 2) HF diet-induced obese control (HF), and 3) HF_RSV. Body weight and food intake were monitored daily. Fasting glucose, insulin, and adiponectin in serum and lipid profiles in serum and liver were analyzed. In addition, the autophagic process was investigated using transmission electron microscopy (TEM). Body weight and food intake were not affected by RSV treatment. Impaired glucose control accompanied by DIO was recovered with RSV as shown by lower levels of fasting serum glucose and insulin when compared with HF obese controls. In addition, RSV treatment resulted in increased levels of serum adiponectin, however, indices of lipid profile in serum and livers were reduced. Results of TEM analysis showed that a HF diet induced excessive autophagy with the presence of double-membrane autophagosomes, which was ameliorated by RSV. The regulatory effect of RSV on autophagy was confirmed by the altered LC3-II formation, which increased with a HF diet and was decreased by RSV treatment. These results suggest that RSV treatment improves glucose control and lipid profile and these beneficial effects may be mediated by an altered autophagic process.