scholarly journals Celastrol delays hepatic steatosis and carcinogenesis in a rapid AKT/c-Met-transfected hepatocellular carcinoma modelviasuppressing fatty acid synthase expression and AKT/ERK phosphorylation

RSC Advances ◽  
2018 ◽  
Vol 8 (25) ◽  
pp. 13976-13983 ◽  
Author(s):  
Junjie Hu ◽  
Xin Li ◽  
Junxuan Zhou ◽  
Cong Zhang ◽  
Guohua Zheng ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Fatty Acid ◽  
Hepatic Steatosis ◽  
Fatty Acid Synthase ◽  
Erk Phosphorylation ◽  
Co Activation

In this study, the effect of celastrol on a rapid HCC model featuring co-activation of AKT/c-Met oncogenes in mice was studied.

Ezetimibe prevents hepatic steatosis induced by a high-fat but not a high-fructose diet

2013 ◽  
Vol 305 (2) ◽  
pp. E293-E304 ◽  
Author(s):  
Masateru Ushio ◽  
Yoshihiko Nishio ◽  
Osamu Sekine ◽  
Yoshio Nagai ◽  
Yasuhiro Maeno ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Liver Disease ◽  
Hepatic Steatosis ◽  
High Fat Diet ◽  
Fatty Acid Synthase ◽  
Binding Protein ◽  
High Fat ◽  
High Fructose Diet ◽  
High Fructose ◽  
Element Binding Protein

Nonalcoholic fatty liver disease is the most frequent liver disease. Ezetimibe, an inhibitor of intestinal cholesterol absorption, has been reported to ameliorate hepatic steatosis in human and animal models. To explore how ezetimibe reduces hepatic steatosis, we investigated the effects of ezetimibe on the expression of lipogenic enzymes and intestinal lipid metabolism in mice fed a high-fat or a high-fructose diet. CBA/JN mice were fed a high-fat diet or a high-fructose diet for 8 wk with or without ezetimibe. High-fat diet induced hepatic steatosis accompanied by hyperinsulinemia. Treatment with ezetimibe reduced hepatic steatosis, insulin levels, and glucose production from pyruvate in mice fed the high-fat diet, suggesting a reduction of insulin resistance in the liver. In the intestinal analysis, ezetimibe reduced the expression of fatty acid transfer protein-4 and apoB-48 in mice fed the high-fat diet. However, treatment with ezetimibe did not prevent hepatic steatosis, hyperinsulinemia, and intestinal apoB-48 expression in mice fed the high-fructose diet. Ezetimibe decreased liver X receptor-α binding to the sterol regulatory element-binding protein-1c promoter but not expression of carbohydrate response element-binding protein and fatty acid synthase in mice fed the high-fructose diet, suggesting that ezetimibe did not reduce hepatic lipogenesis induced by the high-fructose diet. Elevation of hepatic and intestinal lipogenesis in mice fed a high-fructose diet may partly explain the differences in the effect of ezetimibe.

scholarly journals Arazyme Suppresses Hepatic Steatosis and Steatohepatitis in Diet-Induced Non-Alcoholic Fatty Liver Disease-Like Mouse Model

2019 ◽  
Vol 20 (9) ◽  
pp. 2325 ◽  
Author(s):  
Hua Li ◽  
Wonbeak Yoo ◽  
Hye-Mi Park ◽  
Soo-Youn Lim ◽  
Dong-Ha Shin ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Liver Disease ◽  
Fatty Liver ◽  
Hepatic Steatosis ◽  
Fatty Liver Disease ◽  
Fatty Acid Synthase ◽  
Regulatory Element ◽  
Diet Group ◽  
Alcoholic Fatty Liver ◽  
Alcoholic Fatty Liver Disease

Arazyme, a metalloprotease from the spider Nephila clavata, exerts hepatoprotective activity in CCL4-induced acute hepatic injury. This study investigated the hepatoprotective effects in high-fat diet (HFD)-induced non-alcoholic fatty liver disease-like C57BL/6J mice. The mice were randomly divided into four groups (n = 10/group): the normal diet group, the HFD group, the arazyme group (HFD with 0.025% arazyme), and the milk thistle (MT) group (HFD with 0.1% MT). Dietary supplementation of arazyme for 13 weeks significantly lowered plasma triglyceride (TG) and non-esterified fatty acid levels. Suppression of HFD-induced hepatic steatosis in the arazyme group was caused by the reduced hepatic TG and total cholesterol (TC) contents. Arazyme supplementation decreased hepatic lipogenesis-related gene expression, sterol regulatory element-binding transcription protein 1 (Srebf1), fatty acid synthase (Fas), acetyl-CoA carboxylase 1 (Acc1), stearoyl-CoA desaturase-1 (Scd1), Scd2, glycerol-3-phosphate acyltransferase (Gpam), diacylglycerol O-acyltransferase 1 (Dgat1), and Dgat2. Arazyme directly reduced palmitic acid (PA)-induced TG accumulation in HepG2 cells. Arazyme suppressed macrophage infiltration and tumor necrosis factor α (Tnfa), interleukin-1β (Il1b), and chemokine-ligand-2 (Ccl2) expression in the liver, and inhibited secretion of TNFα and expression of inflammatory mediators, Tnfa, Il1b, Ccl2, Ccl3, Ccl4, and Ccl5, in PA-induced RAW264.7 cells. Arazyme effectively protected hepatic steatosis and steatohepatitis by inhibiting SREBP-1-mediated lipid accumulation and macrophage-mediated inflammation.

Effects of Viola mandshurica on Atherosclerosis and Hepatic Steatosis in ApoE−∕− via the AMPK Pathway

2017 ◽  
Vol 45 (04) ◽  
pp. 757-772 ◽  
Author(s):  
Sun Haeng Park ◽  
Yoon-Young Sung ◽  
Kyoung jin Nho ◽  
Dong Sun Kim ◽  
Ho Kyoung Kim
Keyword(s):  
Fatty Acid ◽  
Hepatic Steatosis ◽  
Adhesion Molecules ◽  
Adhesion Molecule ◽  
Lipid Accumulation ◽  
Fatty Acid Synthase ◽  
Inflammatory Responses ◽  
Water Extract ◽  
Intercellular Adhesion Molecule ◽  
Ampk Pathway

Atherosclerosis was previously thought to be a disease that primarily involves lipid accumulation in the arterial wall. In this report, we investigated the effect of Viola mandshurica W. Becker (V. mandshurica) water extract on atherosclerosis in apolipoprotein E deficient (ApoE[Formula: see text]) mice. The administration of V. mandshurica to high-fat diet-fed mice reduced body weight, liver weight, and serum levels of lipids (total cholesterol, low-density lipoprotein-cholesterol, triglycerides), glucose, alanine transaminase, and aspartate transaminase. Histopathologic analyses of the aorta and liver revealed that V. mandshurica attenuated atherosclerotic lesions and reduced lipid accumulation, inflammatory responses and fatty acid synthesis. V. mandshurica also increased phosphorylation of adenosine monophosphate-activated protein kinase (AMPK), thereby reducing acetyl-CoA carboxylase (ACC) in liver tissue and inhibiting sterol regulatory element-binding protein 1c (SREBP-1c). V. mandshurica reduced protein expression levels of adhesion molecules (intercellular adhesion molecule-1, vascular cell adhesion molecule-1, and E-selectin) as well as ACC, fatty acid synthase, and SREBP-1c. In addition, quantitative analysis of V. mandshurica by high-performance liquid chromatography revealed the presence of esculetin and scopoletin. Esculetin and scopoletin reduced adhesion molecules in human aortic smooth muscle cells. Our results indicate that the anti-atherosclerotic effects of V. mandshurica may be associated with activation of the AMPK pathway. Therefore, AMPK-dependent phosphorylation of SREBP-1c by V. mandshurica may be an effective therapeutic strategy for combatting atherosclerosis and hepatic steatosis.

scholarly journals Fisetin Protects Against Hepatic Steatosis Through Regulation of the Sirt1/AMPK and Fatty Acid β-Oxidation Signaling Pathway in High-Fat Diet-Induced Obese Mice

2018 ◽  
Vol 49 (5) ◽  
pp. 1870-1884 ◽  
Author(s):  
Chian-Jiun Liou ◽  
Ciao-Han Wei ◽  
Ya-Ling Chen ◽  
Ching-Yi Cheng ◽  
Chia-Ling Wang ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Lipid Metabolism ◽  
Hepatic Steatosis ◽  
Lipid Accumulation ◽  
High Fat Diet ◽  
Fatty Acid Synthase ◽  
Epididymal Adipose Tissue ◽  
Obese Mice ◽  
High Fat

Background/Aims: Fisetin is a naturally abundant flavonoid isolated from various fruits and vegetables that was recently identified to have potential biological functions in improving allergic airway inflammation, as well as anti-oxidative and anti-tumor properties. Fisetin has also been demonstrated to have anti-obesity properties in mice. However, the effect of fisetin on nonalcoholic fatty liver disease (NAFLD) is still elusive. Thus, the present study evaluated whether fisetin improves hepatic steatosis in high-fat diet (HFD)-induced obese mice and regulates lipid metabolism of FL83B hepatocytes in vitro. Methods: NAFLD was induced by HFD in male C57BL/6 mice. The mice were then injected intraperitoneally with fisetin for 10 weeks. In another experiment, FL83B cells were challenged with oleic acid to induce lipid accumulation and treated with various concentrations of fisetin. Results: NAFLD mice treated with fisetin had decreased body weight and epididymal adipose tissue weight compared to NAFLD mice. Fisetin treatment also reduced liver lipid droplet and hepatocyte steatosis, alleviated serum free fatty acid, and leptin concentrations, significantly decreased fatty acid synthase, and significantly increased phosphorylation of AMPKα and the production of sirt-1 and carnitine palmitoyltransferase I in the liver tissue. In vitro, fisetin decreased lipid accumulation and increased lipolysis and β-oxidation in hepatocytes. Conclusion: This study suggests that fisetin is a potential novel treatment for alleviating hepatic lipid metabolism and improving NAFLD in mice via activation of the sirt1/AMPK and β-oxidation pathway.

scholarly journals Phloretin ameliorates hepatic steatosis through regulation of lipogenesis and Sirt1/AMPK signaling in obese mice

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Chian-Jiun Liou ◽  
Shu-Ju Wu ◽  
Szu-Chuan Shen ◽  
Li-Chen Chen ◽  
Ya-Ling Chen ◽  
...  
Keyword(s):  
Oleic Acid ◽  
Fatty Acid ◽  
Hepatic Steatosis ◽  
Lipid Accumulation ◽  
Hepg2 Cells ◽  
Fatty Acid Synthase ◽  
Regulatory Element ◽  
Liver Lipid ◽  
Obese Mice ◽  
Alcoholic Fatty Liver

Abstract Background Phloretin is isolated from apple trees and could increase lipolysis in 3T3-L1 adipocytes. Previous studies have found that phloretin could prevent obesity in mice. In this study, we investigated whether phloretin ameliorates non-alcoholic fatty liver disease (NAFLD) in high-fat diet (HFD)-induced obese mice, and evaluated the regulation of lipid metabolism in hepatocytes. Methods HepG2 cells were treated with 0.5 mM oleic acid to induce lipid accumulation, and then treated with phloretin to evaluate the molecular mechanism of lipogenesis. In another experiment, male C57BL/6 mice were fed normal diet or HFD (60% fat, w/w) for 16 weeks. After the fourth week, mice were treated with or without phloretin by intraperitoneal injection for 12 weeks. Results Phloretin significantly reduced excessive lipid accumulation and decreased sterol regulatory element-binding protein 1c, blocking the expression of fatty acid synthase in oleic acid-induced HepG2 cells. Phloretin increased Sirt1, and phosphorylation of AMP activated protein kinase to suppress acetyl-CoA carboxylase expression, reducing fatty acid synthesis in hepatocytes. Phloretin also reduced body weight and fat weight compared to untreated HFD-fed mice. Phloretin also reduced liver weight and liver lipid accumulation and improved hepatocyte steatosis in obese mice. In liver tissue from obese mice, phloretin suppressed transcription factors of lipogenesis and fatty acid synthase, and increased lipolysis and fatty acid β-oxidation. Furthermore, phloretin regulated serum leptin, adiponectin, triglyceride, low-density lipoprotein, and free fatty acid levels in obese mice. Conclusions These findings suggest that phloretin improves hepatic steatosis by regulating lipogenesis and the Sirt-1/AMPK pathway in the liver.

P0278 : Hepatic steatosis and high circulating free fatty acid levels promote growth and invasiveness of hepatocellular carcinoma

2015 ◽  
Vol 62 ◽  
pp. S411
Author(s):  
A. Koch ◽  
C. Dorn ◽  
W. Thasler ◽  
M. Mïller ◽  
A. Bosserhoff ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Fatty Acid ◽  
Free Fatty Acid ◽  
Hepatic Steatosis

scholarly journals Pathogenetic, Prognostic, and Therapeutic Role of Fatty Acid Synthase in Human Hepatocellular Carcinoma

2019 ◽  
Vol 9 ◽  
Author(s):  
Li Che ◽  
Panagiotis Paliogiannis ◽  
Antonio Cigliano ◽  
Maria G. Pilo ◽  
Xin Chen ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Fatty Acid ◽  
Fatty Acid Synthase ◽  
Human Hepatocellular Carcinoma ◽  
Therapeutic Role

scholarly journals Ishige okamurae Extract Suppresses Obesity and Hepatic Steatosis in High Fat Diet-Induced Obese Mice

Nutrients ◽  
2018 ◽  
Vol 10 (11) ◽  
pp. 1802 ◽  
Author(s):  
Young-Jin Seo ◽  
Kippeum Lee ◽  
Ji-Hyeon Song ◽  
Sungwoo Chei ◽  
Boo-Yong Lee
Keyword(s):  
Fatty Acid ◽  
Hepatic Steatosis ◽  
High Fat Diet ◽  
Fatty Acid Synthase ◽  
Metabolic Diseases ◽  
Binding Protein ◽  
Regulatory Element ◽  
Hormone Sensitive Lipase ◽  
High Fat ◽  
Ishige Okamurae

Obesity is caused by the expansion of white adipose tissue (WAT), which stores excess triacylglycerol (TG), this can lead to disorders including type 2 diabetes, atherosclerosis, metabolic diseases. Ishige okamurae extract (IOE) is prepared from a brown alga and has anti-oxidative properties. We investigated the detailed mechanisms of the anti-obesity activity of IOE. Treatment with IOE blocked lipid accumulation by reducing expression of key adipogenic transcription factors, such as CCAAT/enhancer-binding protein alpha (C/EBPα) and peroxisome proliferator-activated receptor gamma (PPARγ), in 3T3-L1 cells. Administration of IOE to high fat diet (HFD)-fed mice inhibited body and WAT mass gain, attenuated fasting hyperglycemia and dyslipidemia. The obesity suppression was associated with reductions in expression of adipogenic proteins, such as C/EBPα and PPARγ, increases in expression of lipolytic enzymes, such as adipose triglyceride lipase (ATGL) and hormone-sensitive lipase (HSL), in WAT of HFD-fed mice. In addition, IOE-treated mice had lower hepatic TG content, associated with lower protein expression of lipogenic genes, such as diglyceride acyltransferase 1 (DGAT1), sterol regulatory element-binding protein 1 (SREBP1), fatty acid synthase (FAS). IOE treatment also reduced serum free fatty acid concentration, probably through the upregulation of β-oxidation genes, suggested by increases in AMPKα and CPT1 expression in WAT and liver. In summary, IOE ameliorates HFD-induced obesity and its related metabolic disease, hepatic steatosis, by regulating multiple pathways.

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