• Journal of Physiology & Pathology in Korean Medicine
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• v.27 no.1
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• pp.99-106
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• 2013

We investigated the effects of gambigyeongsinhwan(GGH)(4) on body weight and non-alcoholic fatty liver disease(NAFLD) examined whether blood total cholesterol, LDL-cholesterol, free fatty acid and triglyceride levels and hepatic lipid accumulation are inhibited by it in high fat diet-fed obese male mice. 8 weeks old, high fat diet-fed obese male mice were divided into 5 groups: C57BL/6N normal, control, GGH(4)-1, GGH(4)-2 and GGH(4)-3. After mice were treated with GGH(4) for 8 weeks, we measured body weight gain, food intake, feeding efficiency ratio, fat weight, plasma ALT, leptin and lipid levels. We also did histological analysis for liver and fat on the mice. Compared with controls, GGH(4)-treated mice had lower body weight gain and adipose tissue weight, the magnitudes of which were prominent in GGH(4)-2. Compared with controls, GGH(4)-treated mice had lower feeding efficiency ratio and blood leptin level, the magnitudes of which was prominent in GGH(4)-2. Compared with controls, GGH(4)-treated mice had lower blood plasma total cholesterol, LDL-cholesterol, free fatty acid and triglyceride levels. Compared with controls, GGH(4)-2 treated mice had lower blood plasma ALT concentration. Consistent with their effects on body weight gain, the size of adipocytes were significantly decreased by GGH(4), whereas the adipocyte number per unit area was significantly increased, suggesting that GGH(4) decreased the number of large adipocytes. Hepatic lipid accumulation was decreased by GGH(4). In conclusion, these results suggest that GGH(4) exhibits anti-obesity effects through the modulation of feeding efficiency ratio and plasma obesity parameters. Moreover, it seems that GGH(4) also contributes to improve NAFLD through the regulation of plasma ALT and hepatic triglyceride accumulation.

• Journal of Nutrition and Health
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• v.56 no.6
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• pp.629-640
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• 2023

Purpose: Non-alcoholic fatty liver disease (NAFLD) is characterized by the accumulation of fat in the liver which is not a result of excessive alcohol consumption. Its global prevalence was estimated to be approximately 32% in the years 1994-2019. More than half of obese individuals and patients with diabetes are reported to have NAFLD as a comorbidity. This study aimed to investigate the impact of the autumn olive (Elaeagnus umbellata Thunb.) berry on insulin resistance and steatosis in rats fed a high-fructose diet. Methods: Six-week-old Wistar rats were divided into four groups. The control group received a diet consisting of 65% corn starch, while the fructose and experimental groups were fed a diet comprising 65% fructose (FRU) and an FRU diet containing 0.5% (low-dose autumn olive berry group; LAO) or 1.0% (high-dose autumn olive berry group; HAO) ethanol extract of autumn olive berry, respectively, for 10 weeks. Results: The HAO group exhibited significantly lower blood glucose levels compared to the fructose-fed group. Both the LAO and HAO groups showed a substantial reduction in serum insulin levels and insulin resistance when compared to the fructose-fed group. The consumption of LAO and HAO significantly ameliorated dyslipidemia and reduced the levels of triglycerides in the liver compared to the fructose-fed group. Additionally, the consumption of HAO resulted in lower serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activities compared to the fructose group. The hepatic expression of the sterol regulatory element-binding protein-1c (SREBP-1c) and carbohydrate-responsive element-binding protein (ChREBP) was significantly reduced in the LAO and HAO groups compared to the fructose group. Conclusion: Autumn olive berries improved steatosis by ameliorating insulin resistance and down-regulating the lipogenesis proteins in rats fed on high fructose diet.

• Nutrition Research and Practice
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• v.16 no.6
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• pp.716-728
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• 2022

BACKGROUND/OBJECTIVES: An imbalanced adipokine profile in obesity increases the susceptibility to obesity-related cardiometabolic alterations, including type 2 diabetes, hypertension, dyslipidemia, and non-alcoholic fatty liver disease. The mulberry plant has been reported to have health benefits, such as hypolipidemic and hepatoprotective effects. This study examined the effects of a mulberry (Morus alba L.) fruit ethanol extract (MBEE) on dyslipidemia, liver steatosis, and adipokine imbalance in response to a high-fat diet. MATERIALS/METHODS: Male Sprague-Dawley rats were assigned to one of 4 groups containing 6 rats each and fed either a control diet (CON), a high-fat diet (HFD), or a high-fat diet with MBEE of 150 mg/kg/day (LMB) or 300 mg/kg/day (HMB). The triglyceride (TG), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), alanine aminotransferase (ALT), and aspartate aminotransferase (AST) activities were measured spectrophotometrically. The leptin, adiponectin, and plasminogen activator inhibitor-1 (PAI-1) levels were determined by an enzyme-linked immunosorbent assay. RESULTS: The plasma TG levels were similar in the 4 groups. Plasma cholesterol and low-density lipoprotein cholesterol (LDL-C) levels and TC/HDL-C ratio increased in the HFD group compared with the CON group, whereas those values decreased in the LMB group (P < 0.05), indicating that MBEE had a plasma lipid-lowering effect. HDL-C decreased in the HFD group, but MBEE did not affect the HDL-C level. The HFD rats significantly increased hepatic TG and cholesterol levels and plasma ALT and AST activities compared to the CON group. The hepatic TG level and ALT and AST activities were reduced markedly by the MBEE treatment. The HFD group showed a higher PAI-1 level, whereas MBEE treatment, especially in the HMB group, significantly reduced leptin level, and leptin/adiponectin and PAI-1/ adiponectin ratios. These findings suggest that MBEE altered the imbalance between the pro-and anti-inflammatory adipokines to a more anti-inflammatory state. CONCLUSIONS: MBEE could protect against abnormal lipid metabolism and hepatic steatosis induced by a high-fat diet, lowering plasma cholesterol, LDL-C and TC/HDL-C, and hepatic TG. These findings are associated with the regulating effect of MBEE on the leptin/adiponectin and PAI-1/adiponectin ratios.

• 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.

• Journal of Nutrition and Health
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• v.55 no.2
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• pp.227-239
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• 2022

Purpose: This study investigated the effects of water-soluble mulberry leaf extract (ME) on hepatic lipid accumulation in high-fat diet-fed rats via the regulation of hepatic microRNA (miR)-221/222 and inflammation. Methods: Male Sprague-Dawley rats (4 weeks old) were randomly divided into 3 groups (n = 7 each) and fed with 10 kcal% low-fat diet (LF), 45 kcal% high-fat diet (HF), or HF + 0.8% ME for 14 weeks. Lipid profiles and cytokine levels of the liver and serum were measured using commercial enzymatic colorimetric and enzyme-linked immunosorbent assay, respectively. The messenger RNA (mRNA) and miR levels in liver tissue were assayed by real-time quantitative reverse-transcription polymerase chain reaction. Results: Supplementation of ME reduces body weight and improves the liver and serum lipid profiles as compared to the HF group. The mRNA levels of hepatic peroxisome proliferator-activated receptor-gamma, sterol regulatory element binding protein-1c, fatty acid synthase, and fatty acid translocase, which are genes involved in lipid metabolism, were significantly downregulated in the ME group compared to the HF group. In contrast, the mRNA level of hepatic carnitine palmitoyl transferase-1 (involved in fatty acid oxidation) was upregulated by ME supplementation. Furthermore, administration of ME significantly downregulated the mRNA levels of inflammatory mediators such as hepatic tumor necrosis factor alpha (TNF-α), interleukin 6 (IL-6), monocyte chemoattractant protein-1, and inducible nitric oxide synthase. The serum levels of TNF-α, IL-6, and nitric oxide were also significantly reduced in ME group compared to the HF group. Expression of hepatic miR-221 and miR-222, which increase in the inflammatory state of the liver, were also significantly inhibited in the ME group compared to the HF group. Conclusion: These results indicate that ME has the potential to improve hepatic lipid accumulation in high-fat diet-fed rats via modulation of inflammatory mediators and hepatic miR-221/222 expressions.

• 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.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.