• Molecules and Cells
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• v.44 no.2
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• pp.116-125
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• 2021

Cardiovascular diseases (CVDs) are the most common cause of death in patients with nonalcoholic fatty liver disease (NAFLD) and dyslipidemia is considered at least partially responsible for the increased CVD risk in NAFLD patients. The aim of the present study is to understand how hepatic de novo lipogenesis influences hepatic cholesterol content as well as its effects on the plasma lipid levels. Hepatic lipogenesis was induced in mice by feeding a fat-free/high-sucrose (FF/HS) diet and the metabolic pathways associated with cholesterol were then analyzed. Both liver triglyceride and cholesterol contents were significantly increased in mice fed an FF/HS diet. Activation of fatty acid synthesis driven by the activation of sterol regulatory element binding protein (SREBP)-1c resulted in the increased liver triglycerides. The augmented cholesterol content in the liver could not be explained by an increased cholesterol synthesis, which was decreased by the FF/HS diet. HMG-CoA reductase protein level was decreased in mice fed an FF/HS diet. We found that the liver retained more cholesterol through a reduced excretion of bile acids, a reduced fecal cholesterol excretion, and an increased cholesterol uptake from plasma lipoproteins. Very low-density lipoproteintriglyceride and -cholesterol secretion were increased in mice fed an FF/HS diet, which led to hypertriglyceridemia and hypercholesterolemia in Ldlr-/- mice, a model that exhibits a more human like lipoprotein profile. These findings suggest that dietary cholesterol intake and cholesterol synthesis rates cannot only explain the hypercholesterolemia associated with NAFLD, and that the control of fatty acid synthesis should be considered for the management of dyslipidemia.

• Biomolecules & Therapeutics
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• v.21 no.4
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• pp.264-269
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• 2013

Silymarin has been introduced fairly recently as a hepatoprotective agent. But its mechanisms of action still have not been well established. The aim of this study was to make alcoholic fatty liver model of rats in a short time and investigate silymarin's protective effects and possible mechanisms on alcoholic fatty liver for rats. The model of rat's alcoholic fatty liver was induced by intragastric infusion of ethanol and high-fat diet for six weeks. Histopathological changes were assessed by hematoxylin and eosin staining (HE). The activities of alanine transarninase (ALT) and aspartate aminotransferase (AST), the levels of total bilirubin (TBIL), total cholesterol (TC) and triglyceride (TG) in serum were detected with routine laboratory methods using an autoanalyzer. The activities of superoxide dismutase (SOD) and glutathione peroxidase (GPx) and the level of malondialdehyde (MDA) in liver homogenates were measured by spectrophotometry. The TG content in liver tissue was determined by spectrophotometry. The expression of nuclear factor-${\kappa}B$ (NF-${\kappa}B$), intercellular adhesion molecule-1 (ICAM-1) and interleukin-6 (IL-6) in the liver were analyzed by immunohistochemistry. Silymarin effectively protected liver from alcohol-induced injury as evidenced by improving histological damage situation, reducing ALT and AST activities and TBIL level in serum, increasing SOD and GPx activities and decreasing MDA content in liver homogenates and reducing TG content in liver tissue. Additionally, silymarin markedly downregulated the expression of NF-${\kappa}B$ p65, ICAM-1 and IL-6 in liver tissue. In conclusion, Silymarin could protect against the liver injury caused by ethanol administration. The effect may be related to alleviating lipid peroxidation and inhibiting the expression of NF-${\kappa}B$.

• Biomedical Science Letters
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• v.17 no.1
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• pp.13-20
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• 2011

The peroxisome proliferator-activated receptor ${\alpha}$ ($PPAR{\alpha}$) is a nuclear transcription factor that plays a central role in lipid and lipoprotein metabolism. To investigate whether swim training improves obesity and lipid metabolism through $PPAR{\alpha}$ activation in female sham-operated (Sham) and ovariectomized (OVX) mice, we measured body weight, visceral adipose tissue mass, serum free fatty acid at 6 weeks as well as the expression of hepatic $PPAR{\alpha}$ target genes involved in fatty acid oxidation. Swim-trained mice had decreased body weight, visceral adipose tissue mass and serum free fatty acid levels compared to high fat diet fed control mice in both female Sham and OVX mice. These reductions were more prominent in OVX than in Sham mice. Swim training significantly increased hepatic mRNA levels of $PPAR{\alpha}$ target genes responsible for mitochondrial fatty acid ${\beta}$-oxidation, such as carnitine palmitoyltransgerase-1 (CPT-1), very long chain acyl-CoA dehydrogenase (VLCAD), and medium chain acyl-CoA dehydrogenase (MCAD) in OVX mice. However, swim trained female Sham mice did not increase hepatic mRNA levels of $PPAR{\alpha}$ target genes responsible for mitochondrial fatty acid ${\beta}$-oxidation compared to Sham control mice. These results indicate that swim training differentially regulates body weight and adipose tissue mass between OVX and Sham mice, at least in part due to differences in liver $PPAR{\alpha}$ activation.

• Interdisciplinary Bio Central
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• v.5 no.4
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• pp.9.1-9.7
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• 2013

Introduction: Tumor necrosis factor receptor-associated protein 1 (TRAP1) is a mitochondrial heat shock protein (HSP), which belongs to HSP90 family. It plays important roles in regulating mitochondrial integrity, protecting against oxidative stress, and inhibiting cell death. Recent studies suggest that TRAP1 is linked to mitochondria and its metabolism. In this study, we established TRAP1 transgenic mice and performed partial hepatectomy (PH) on wild-type (WT) and TRAP1 transgenic mice to investigate the function of TRAP1 during liver regeneration. Results and Discussion: We found that TRAP1 was highly expressed in liver as well as kidney. In addition, liver regeneration slightly decreased together with increased fatty liver and inflammation at 72 hr after PH in TRAP1 transgenic mice compared with WT control group mice. Concomitantly, we observed decreased levels of p38 protein in TRAP1 transgenic mice compared with WT control group mice. These results suggest that TRAP1 plays a critical role in liver energy balance by regulating lipid accumulation during liver regeneration. Conclusions and Prospects: To our knowledge, we reported, for the first time, that liver regeneration slightly reduced together with increased fat accumulations after PH in TRAP1 transgenic mice compared with WT control group mice. Concomitantly, we observed decreased levels of p38 protein in TRAP1 transgenic mice compared with WT control group mice. Overexpression of TRAP1 might affect liver regeneration via disturbing mitochondrial function leading to fatty liver in vivo.

• Herbal Formula Science
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• v.28 no.2
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• pp.179-187
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• 2020

Objectives : This study investigated the hepatoprotective effects effects of Jageum-jung extract on alcohol-induced liver disease mice model. Methods : Alcoholic liver disease was induced by Ethanol in C57/BL6 male mice, which were fed Lieber-DeCarli liquid diet containing ethanol. Jageum-jung (100,200 and 300 mg/kg bw/day) were orally administered daily in the alcoholic fatty liver disease mice for 16 days. Results : The results indicate that Jageum-jung promotes hepatoprotective effects by significantly reducing aspartate transaminase (AST) and alanine transaminase (ALT) levels as indicators of liver damage in the serum. Furthermore, Jageum-jung decreased accumulation of triglyceride and total cholesterol, increased levels of superoxide dismutase (SOD) and glutathione (GSH) in the serum of the alcoholic fatty liver disease mice model. Additionally, it improved the serum alcohol dehydrogenase (ADH) activity. Conclusions : This study confirmed the anti-oxidative and hangover elimination effects of Jageum-jung extract, and suggests the possibility of using Jageum-jung to treat alcholic liver disease.

• Herbal Formula Science
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• v.26 no.2
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• pp.113-122
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• 2018

Objectives : Alcoholic fatty liver is an early and reversible consequence of excessive alcohol consumption. The initial hepatocyte cell death stimulates subsequent inflammatory responses, leading to further liver injury and fibrosis. The objective of this study is to investigate the effects of Injinsaryung-san extract on the alcoholic fatty liver by chronic EtOH administration. Method : 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+IS group, treated with ethanol+Injinsaryung-san extract (n=10). For oral administration of ethanol in Control and Sample 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 Injinsaryung-san extract daily for 8 weeks. Results : The levels of hepatic marker such as aspartate aminotransferase and alanine aminotransferase were altered. Histopathological changes were reduced and the expression of tumor necrosis $factor-{\alpha}$ ($TNF-{\alpha}$) was markedly attenuated by Injinsaryung-san extract. Conclusion : These data suggest that Injinsaryung-san extract could be effective in protecting the liver from alcoholic fatty liver. The hepatoprotective mechanisms of Injinsaryung-san may be related to attenuation of $TNF-{\alpha}$ protein, as well as to the inhibition of inflammatory response in the liver. Therefore, Injinsaryung-san can be a candidate to protect against alcoholic fatty liver.

• Pediatric Gastroenterology, Hepatology & Nutrition
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• v.24 no.2
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• pp.187-196
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• 2021

Purpose: The rising prevalence of childhood obesity in the past decades has caused non-alcoholic fatty liver disease (NAFLD) to become the most common cause of pediatric chronic liver disease worldwide. This study was aimed at determining the effect of vitamin D (Vit D) on ultrasonography and laboratory indices of NAFLD and some blood biochemical indicators in children. Methods: In this interventional study liver ultrasonography was performed in 200 children with overweight and obesity. A 108 had fatty liver among which 101 were randomly divided into two groups of study (n=51) and control (n=50). The study group was treated with Vit D, 50000 U once a week whereas the control group received placebo with the same dose and package, both for 12 weeks. At the end of the intervention lab tests and ultrasound study was performed once again to evaluate the response to treatment. Results: It was found out that Vit D supplementation improved the fatty liver grade in the study group. The mean changes in hemoglobin (Hb), uric acid, highdensity lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), insulin, albumin and alanine aminotransferase (ALT) was significantly higher in the study group compared to controls (p<0.05). After the intervention and means adjustment, a significant difference was obtained in HDL-C, insulin, LDL-C and homeostasis model assessment of insulin resistance (HOMA-IR) between the two groups. Conclusion: Vit D supplementation in addition to improving the fatty liver grade in ultrasonography and increasing the blood Vit D level, increases the HDL and Hb level besides decreasing uric acid, LDL, HOMA-IR, insulin and ALT levels.

• Asian-Australasian Journal of Animal Sciences
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• v.25 no.8
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• pp.1169-1177
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• 2012

An experiment was conducted to determine the effects of different amounts of dietary linoleic acid (LA) on growth performance, serum biochemical traits, meat quality, fatty acids composition of muscle and liver, acetyl-CoA carboxylase (ACC) and carnitine palmitoyl transferase 1 (CPT 1) mRNA expression in the liver of 9 wks old to 13 wks old growing meat rabbits. One hundred and fifty 9 wks old meat rabbits were allocated to individual cages and randomly divided into five groups. Animals in each group were fed with a diet with the following LA addition concentrations: 0, 3, 6, 9 and 12 g/kg diet (as-fed basis) and LA concentrations were 0.84, 1.21, 1.34, 1.61 and 1.80% in the diet, respectively. The results showed as follows: the dietary LA levels significantly affected muscle color of LL included $a^*$ and $b^*$ of experimental rabbits (p<0.05). The linear effect of LA on serum high density lipoprotein cholesterol was obtained (p = 0.0119). The saturated fatty acids (SFAs) and monounsaturated fatty acids (MUFAs) contents of LL decreased and the polyunsaturated fatty acids (PUFAs) content of LL increased with dietary LA increase (p<0.0001). The PUFA n-6 content and PUFA n-3 content in the LL was significantly affected by the dietary LA levels (p<0.01, p<0.05). The MUFAs content in the liver decreased and the PUFAs contents in the liver increased with dietary LA increase (p<0.0001). The PUFA n-6 content and the PUFA n-6/n-3 ratio in the liver increased and PUFA n-3 content in the liver decreased with dietary LA increase (p<0.01). The linear effect of LA on CPT 1 mRNA expression in the liver was obtained (p = 0.0081). In summary, dietary LA addition had significant effects on liver and muscle fatty acid composition (increased PUFAs) of 9 wks old to 13 wks old growing meat rabbits, but had little effects on growth performance, meat physical traits and mRNA expression of liver relative enzyme of experimental rabbits.

• The Korean Journal of Food And Nutrition
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• v.7 no.3
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• pp.192-202
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• 1994

The fatty acid composition of a rapeseed oil being on the market was analyzed and the effect on gain of the body weight and lipid levels in serum and liver tissue of male rats of Sprague-Dawely strain fed the diet containing the rapeseed oil were studied. The fatty acid components of marketed rapeseed oil was oleic acid 29.4%, erucic acid 26.52%, linoleic acid 20.39% and linolenic acid 8.68%. The contents of total lipid in serum W3S Significantly higher in RSO20 group than Contr01 group(P< 0.01) . But that in the liver tissue did 001 show significant differences. The contents of triglyceride in serum was control group 84.14mg/dll, RSO15 group 100.33mg 141 and RSO20 group 122.00mg 141 and showed significant difference between each group, but that in the livertissue did not show significant differences. The contents of phospholipid in serum did not show significant differences. But that in the liver tissue showed significant difference between the control group 8.42mg /g and Rs02o group 7.34mg /g(p<0.001). The contents of total-cholesterol and free-cholesterol in serum and liver tissue of the RSO20 group showed the highest levels compared with control group, but there did not show significant differences. The contents of ester-cholesterol in serum showed significant.

• Journal of Ginseng Research
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• v.32 no.3
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• pp.187-193
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• 2008

The present study was designed to investigate the anti-diabetic effect and mechanism of Korean red ginseng in C57BL/KsJ db/db mice. The db/db mice were divided into three groups: diabetic control group (DC), Korean red ginseng group (KRG, 100 mg/kg) and metformin group (MET, 300 mg/kg), and treated with drugs once per day for 10 weeks. Compared to the DC group, fasting blood glucose levels were decreased by 19.8% in KRG-, 67.7% in MET-treated group. With decreased plasma glucose and insulin levels, the insulin resistance index of the KRG-treated group was reduced by 27.6% compared to the DC group. The HbA1c levels in KRG and MET-treated groups were also decreased by 11.0% and 18.9% compared to that of DC group, respectively. Plasma triglyceride and non-esterified fatty acid levels were decreased by 18.8% and 16.8%, respectively, and plasma adiponectin and leptin levels were increased by 20.6% and 12.1%, respectively, in the KRG-treated group compared to those in DC group. Histological analyses of the liver and fat tissue of mice treated with KRG revealed significantly decreased number of lipid droplets and decreased size of adipocytes compared to the DC group. From the pancreatic islet double-immunofluorescence staining, we observed KRG has increased insulin contents, but decreased glucagon production. To elucidate action mechanism of KRG, effects on AMP-activated protein kinase (AMPK) and its downstream target proteins responsible for fatty acid oxidation and gluconeogenesis were explored in the liver. KRG activated AMPK and acetyl-coA carboxylase (ACC) phosphorylations, resulting in stimulation of fatty acid oxidation. KRG also caused to down regulation of SREBP1a and its target gene expressions such as FAS, SCD1 and GPAT. In summary, our results suggest that KRG exerted the anti-diabetic effect through AMPK activation in the liver of db/db mice.