• Asian-Australasian Journal of Animal Sciences
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• v.14 no.9
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• pp.1331-1341
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• 2001

Dairy cows are prone to fatty liver during the time of periparturient. Despite of the extensive studies, etiology and solutions for fatty liver are still not well known.The liver synthesizes triglycerides (TG) using precursors from bloodstream and secretes TG in form of very low density lipoprotein (VLDL) into bloodstream for the utilization by peripheral tissues. When the amount of TG synthesis exceeds the amount of secretion in VLDL-TG, TG accumulation within the liver occurs. Hepatic VLDL assembly and secretion involve multi-biochemical events.The availabilities of apolipoprotein B (apoB), E (apoE), microsomal triglyceride transfer protein (MTP) and soluble low density lipoprotein (LDL) receptor are now believed to be some of the main regulators for hepatic VLDL assembly and secretion. Studies in transgenic animals show that overexpression of these proteins stimulates VLDL production and secretion, which provides a possibility for alleviating bovine fatty liver by gene therapy. However, many problems remain to be solved to attain this goal. This review focuses on the molecular mechanisms of hepatic VLDL assembly and secretion, and the possibilities and problems of applying the knowledges to solve bovine fatty liver by gene therapy.

• Nutrition Research and Practice
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• v.15 no.4
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• pp.431-443
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• 2021

BACKGROUND/OBJECTIVES: Nobiletin (NOB), a citrus flavonoid, is reported to have beneficial effects on cardiovascular and metabolic health. However, there is limited research investigating the effect of long-term supplementation with low-dose NOB on high-cholesterol diet (HCD)-induced hypercholesterolemia and non-obese nonalcoholic fatty liver disease (NAFLD). Therefore, we investigated the influence of NOB on hypercholesterolemia and NAFLD in HCD-fed mice. SUBJECTS/METHODS: C57BL/6J mice were fed a normal diet (ND) or HCD (35 kcal% fat, 1.25% cholesterol, 0.5% cholic acid) with or without NOB (0.02%) for 20 weeks. RESULTS: HCD feeding markedly reduced the final body weight compared to ND feeding, with no apparent energy intake differences. NOB supplementation suppressed HCD-induced weight loss without altering energy intake. Moreover, NOB significantly decreased the total cholesterol (TC) levels and the low-density lipoprotein (LDL)/very-LDL-cholesterol to TC ratio, and increased the high-density lipoprotein-cholesterol/TC ratio in plasma, compared to those for HCD feeding alone. The plasma levels of inflammatory and atherosclerosis markers (C-reactive protein, oxidized LDL, interleukin [IL]-1β, IL-6, and plasminogen activator inhibitor-1) were significantly lower, whereas those of anti-atherogenic adiponectin and paraoxonase were higher in the NOB-supplemented group than in the HCD control group. Furthermore, NOB significantly decreased liver weight, hepatic cholesterol and triglyceride contents, and lipid droplet accumulation by inhibiting messenger RNA expression of hepatic genes and activity levels of cholesterol synthesis-, esterification-, and fatty acid synthesis-associated enzymes, concomitantly enhancing fatty acid oxidation-related gene expression and enzyme activities. Dietary NOB supplementation may protect against hypercholesterolemia and NAFLD via regulation of hepatic lipid metabolism in HCD-fed mice; these effects are associated with the amelioration of inflammation and reductions in the levels of atherosclerosis-associated cardiovascular markers. CONCLUSIONS: The present study suggests that NOB may serve as a potential therapeutic agent for the treatment of HCD-induced hypercholesterolemia and NAFLD.

• Journal of Nutrition and Health
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• v.55 no.1
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• pp.36-46
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• 2022

Purpose: Quercetin is a polyphenolic flavonoid abundant in many fruits and vegetables. It has potential health-beneficial properties, such as antioxidant, anti-obesity, anti-cancer, anti-diabetic and anti-inflammatory effects. The purpose of this study was to investigate whether the lipid metabolism improvement effect of quercetin affected the regulation of AMP-activated protein kinase (AMPK) activity and microRNA (miR)-21 expression in the liver of mice fed a high-cholesterol diet. Methods: Male C57BL/6J mice were fed with normal diet, quercetin-free diet and diets containing 0.05% or 0.1% quercetin for six weeks. Hypercholesterolemia was induced by adding 1% cholesterol and 0.5% cholic acid to all diets. Serum and liver triglyceride (TG), and total cholesterol (TC) concentrations were analyzed using a commercial enzymatic colorimetric kit. AMPK activity was quantified using an AMPK kinase assay kit. The levels of miR-21 and genes involved in lipid metabolism were measured by real-time quantitative polymerase chain reaction. Results: Supplementation of quercetin reduced serum and hepatic TG and TC levels without changing body weight and food intake. Dietary quercetin significantly inhibited the mRNA levels of hepatic sterol-regulatory element binding protein-1c, acetyl-CoA carboxylase 1 and fatty acid synthesis, which are involved in hepatic lipogenesis. Dietary quercetin enhanced AMPK activity and suppressed miR-21 expression, promoting hepatic lipid accumulation. Conclusion: These results suggest that the lipid-lowering effect of quercetin on the serum and liver of mice may be partially mediated by the regulation of lipogenic gene expression, AMPK activity and miR-21 expression in the liver of mice fed a high-cholesterol diet.

• The Journal of Internal Korean Medicine
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• v.19 no.1
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• pp.3-21
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• 1998

This study was to investigate the effects of Gibangganbang on the liver injury induced dimethylnitrosamine, CCl4, ethanol and partial hepatectomy. Hydroxyproline, hepatic fibrosis, hepatic inflammatory cell infiltration, fatty value, lipidoperoxide levels, glutathione levels, mitotic index, contents of protein in the serum and liver tissues were measured and observed. The results obtained were as follows. 1. The increasing level of hydroxyproline volume induced by dimethylnitrosamine in mice was decreased by the oral administration of Gibangganbang. 2. The degree of hitological fibrosis and hepatic inflammatory cell infiltration induced by $CCl_4$ was decreased by the oral administration of Gibangganbang. 3. The degree of fatty value and the increasing level of lipidoperoxide in liver tissues was decreased by the oral administration of Gibangganbang. 4. The level of glutathione in liver tissues was increasing by the oral administration of Gibangganbang. 5. The increasing level of microsomal lipidoperoxide in vitro assay was decreasing by the oral administration of Gibangganbang. 6. The increasing level of the mitotic index, weight of liver, contents of protein, RNA and DNA synthesis of the liver tissues after partial hepatectomy was activated by the oral administration of Gibangganbang. These results suggest that Gibangganbang not only inhibits liver cirrhotic change and ethanol-induced fatty change but also activates antioxidant enzymes and regeneration ability ocf liver.

• The Journal of Korean Medicine
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• v.22 no.3
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• pp.141-155
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• 2001

Objective : The aim of this study is to investigate the effect of Injin fractions on hepatic fibrosis induced by $TGF-{\beta}1$. Method : $TGF-{\beta}1$ mRNA, protein, $TGF-{\beta}1$ receptor, Smad family and PAI-I mRNA were studied in HepG2 cell, and the proliferation, connective tissue growth factor, fibronectin and collagen type I mRNA in T3891 fibroblast by quantitative RT-PCR, ELISA and thymidine incorporation assay. Results : On $TGF-{\beta}1$ mRNA and protein synthesis in HepG2, $H_2O$, butanol and hexane fractions of Injin showed inhibitory effect in a dose-dependent way. In the study on $TGF-{\beta}1$ receptor, Smad family and PAI-1 mRNA in HepG2, $H_2O$, butanol and hexane fraction of Injin showed inhibitory effect on the expression of PAI-1 in a dose-dependent way. On the proliferation of T3891 fibroblast induced by $TGF-{\beta}1$, $H_2O$, ethylacetate and butanol fractions of Injin showed inhibitory effect. In the study on the factors affected by $TGF-{\beta}1$, $H_2O$, ethylacetate and butanol fractions of Injin showed inhibitory effect on CTGF, and $H_2O$, butanol, chloroform and hexane fractions showed inhibitory effect on the expression of collagen type I, whereas no fraction showed inhibitory effect on the expression of fibronectin Conclusion : These results show that each fraction of Injin acts as a fibrosis inhibitory factor by itself or in combination, ultimately inhibiting liver cirrhosis.

• Journal of the Korean Society of Food Science and Nutrition
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• v.43 no.11
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• pp.1648-1657
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• 2014

In this study, the hepatic lipid-lowering effects and related mechanism of action of sujeonggwa were examined in hypercholesterolemia-induced apoprotein E knockout (apo E ko) mice. Sujeonggwa drink was prepared with cinnamon, ginger, and sugar by modifying the traditional recipe of sujeonggwa. Sugar was partially substituted with either stevia or short chain fructooligosaccharide (scFOS) in order to reduce the calorie content of sujeonggwa, which was measured by descriptive analysis. Apo E ko mice (n=42) were induced to have hypercholesterolemia (plasma total cholesterol concentration >1,000 mg/dL) by administration of a high cholesterol diet for 4 weeks, followed by division into six groups. Experimental groups were orally administered water as a vehicle (normal group), sugar solution (control group), commercially available 'V' sujeonggwa drink (positive control group), or three different types of sujeonggwa drinks (S-sugar, S-stevia, and S-scFOS group) for 6 weeks while high cholesterol diet was provided to all animals. Compared to the control group, concentrations of hepatic triglycerides, total cholesterol, thiobarbituric acid reactive substances, and reactive oxygen species in S-sugar, S-stevia, S-scFOS were significantly reduced (P<0.05), indicating that sujeonggwa had inhibitory effects on hepatic lipid accumulation. Protein expression levels of fatty acid synthase (FAS) and its transcription factor, sterol regulatory element-binding protein (SREBP)-1 responsible for triglyceride synthesis, as well as 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR) and its transcription factor, SREBP-2 responsible for cholesterol synthesis, were also reduced in S-sugar, S-stevia, and S-scFOS groups (P<0.05). These benefits of sujeonggwa were even greater in S-stevia and S-scFOS compared to S-sugar. The beneficial effects of S-stevia on regulation of hepatic lipid metabolism were slightly greater than those of S-scFOS although the differences were not significant. In conclusion, sujeonggwa drinks, especially functional sujeonggwa drinks in which sugar was partially substituted with stevia or scFOS, inhibited hepatic lipid accumulation via suppressing FAS and HMGCR protein expression through down-regulation of SREBP-1 and 2.

• Korean Journal of Food Science and Technology
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• v.51 no.3
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• pp.272-277
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• 2019

The effects of medium-chain enriched diacylglycerol (MCE-DAG) oil on hepatic cholesterol homeostasis were investigated. HepG2 hepatocytes were treated with either 0.5, 1.0, or $1.5{\mu}g/mL$ of MCE-DAG for 48 h. There was no evidence of cytotoxicity by MCE-DAG up to $1.5{\mu}g/mL$. The level of proteins for cholesterol uptake including CLATHRIN and LDL receptor increased by MCE-DAG in a dose-dependent manner (p<0.05). Furthermore, proprotein convertase subtilisin/kexin type 9, an inhibitor of LDLR, was dose-dependently diminished (p<0.05), indicating cholesterol clearance raised. MCE-DAG significantly increased 3-hydroxy-3-methylglutaryl-coenzyme A reductase and acetyl-CoA acetyltransferase2 (p<0.05), required for cholesterol synthesis, and their transcriptional regulator sterol regulatory element-binding protein2 (p<0.05). These findings suggest that given conditions of prolonged sterol fasting in the current study activated both hepatic cholesterol synthesis and clearance by MCE-DAG. However, total intracellular level of cholesterol was not altered by MCE-DAG. Taken together, MCE-DAG has the potential to prevent hypercholesterolemia by increasing hepatic cholesterol uptake without affecting intracellular cholesterol level.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.18
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• pp.7527-7532
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• 2014

Saussurea involucrata is a Mongolian medicinal plant well known for its effects in promoting blood circulation, and anti-inflammation and analgesic functions. Earlier studies reported that Saussurea involucrata has anticancer activity. The purpose of this study was to confirm the anticancer activity of an ethanol extract of Saussurea involucrata against hepatic cancer and elucidate its mechanisms of action. Hepatocellular carcinoma cells were tested in vitro for cytotoxicity, AO/EB staining for apoptotic cells, apoptotic DNA fragmentation and cell cycle distribution in response to Saussurea involucrata extract (SIE). The mRNA expression of caspase-3,-9 and Cdk2 and protein expression of caspase-3,-9, PARP, XIAP, Cdk2 and p21 were analyzed through real time PCR and Western blotting. Treatment with SIE inhibited HepG2 cell proliferation dose- and time-dependently, but SIE only exerted a modest cytotoxic effect on a viability of Chang human liver cells. Cells exposed to SIE showed typical hallmarks of apoptotic cell death. Cell cycle analysis revealed that SIE caused G1-phase arrest in HepG2 cells. In conclusion, Saussurea involucrata ethanol extract has potential cytotoxic and apoptotic effects on human hepatocellular carcinoma cells. Its mechanism of action might be associated with the inhibition of DNA synthesis, cell cycle (G1) arrest and apoptosis induction through up-regulation of the protein expressions of caspase-3,-9 a nd p21, degradation of PARP and down-regulation of the protein expression of Cdk2 and XIAP.

• Preventive Nutrition and Food Science
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• v.21 no.3
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• pp.171-180
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• 2016

Non-alcoholic fatty liver disease (NAFLD) is one of the most prevalent liver diseases associated with an altered lifestyle, besides genetic factors. The control and management of NAFLD mostly depend on lifestyle modifications, due to the lack of a specific therapeutic approach. In this context, we assessed the effect of carrot juice on the development of high fructose-induced hepatic steatosis. For this purpose, male weanling Wistar rats were divided into 4 groups, fed either a control (Con) or high fructose (HFr) diet of AIN93G composition, with or without carrot juice (CJ) for 8 weeks. At the end of the experimental period, plasma biochemical markers, such as triglycerides, alanine aminotransferase, and ${\beta}$-hydroxy butyrate levels were comparable among the 4 groups. Although, the liver injury marker, aspartate aminotransferase, levels in plasma showed a reduction, hepatic triglycerides levels were not significantly reduced by carrot juice ingestion in the HFr diet-fed rats (HFr-CJ). On the other hand, the key triglyceride synthesis pathway enzyme, hepatic stearoyl-CoA desaturase 1 (SCD1), expression at mRNA level was augmented by carrot juice ingestion, while their protein levels showed a significant reduction, which corroborated with decreased monounsaturated fatty acids (MUFA), particularly palmitoleic (C16:1) and oleic (C18:1) acids. Notably, it also improved the long chain n-3 polyunsaturated fatty acid, docosahexaenoic acid (DHA; C22:6) content of the liver in HFr-CJ. In conclusion, carrot juice ingestion decreased the SCD1-mediated production of MUFA and improved DHA levels in liver, under high fructose diet-fed conditions. However, these changes did not significantly lower the hepatic triglyceride levels.

• Journal of Korean Medicine for Obesity Research
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• v.18 no.1
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• pp.19-26
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• 2018

Objectives: Alcoholic fatty liver is a potentially pathologic condition which can progress to steatohepatitis, fibrosis, and cirrhosis. The objective of this study is to investigate the effects of Scutellaria Radix (SR) extract on the alcoholic fatty liver induced by long-term EtOH administration. Results: Male Sprague Dawley rats were used in this study. All animals were randomly divided into Normal group, treated with saline (n=10); EtOH group, treated with ethanol (n=10); EtOH+SR group, treated with ethanol+Scutellaria Radix extract (n=10). For oral administration of ethanol in EtOH and EtOH+SR group, the ethanol was dissolved in distilled water in concentrations of 25% (v/v). Throughout the experiment of 8 week, the rats were allowed free access to water and standard chow. Sample group were administrated by Scutellaria Radix extract daily for 8 weeks. Results: The levels of hepatic marker such as aspartate aminotransferase and alanine aminotransferase were altered. Histopathological changes such as ballooning, fatty and hydropic degeneration were reduced and the expression of tumor necrosis $factor-{\alpha}$ ($TNF-{\alpha}$) was significantly attenuated by Scutellaria Radix extract. Conclusions: These data suggest that Scutellaria Radix extract attenuated the alcoholic simple fatty liver by improving hepatic lipid metabolism via suppression of $TNF-{\alpha}$ protein. Scutellaria Radix could be effective in protecting the liver from alcoholic fatty liver.