scholarly journals Metformin improves nonalcoholic fatty liver disease in obese mice via down-regulation of apolipoprotein A5 as part of the AMPK/LXRα signaling pathway

Oncotarget ◽  
2017 ◽  
Vol 8 (65) ◽  
pp. 108802-108809 ◽  
Author(s):  
Min-Jie Lin ◽  
Wen Dai ◽  
Melanie J. Scott ◽  
Rong Li ◽  
Yi-Qi Zhang ◽  
...  
Keyword(s):  
Liver Disease ◽  
Fatty Liver ◽  
Nonalcoholic Fatty Liver Disease ◽  
Signaling Pathway ◽  
Fatty Liver Disease ◽  
Obese Mice ◽  
Down Regulation ◽  
Nonalcoholic Fatty Liver ◽  
Apolipoprotein A5

scholarly journals SGL 121 Attenuates Nonalcoholic Fatty Liver Disease through Adjusting Lipid Metabolism Through AMPK Signaling Pathway

2020 ◽  
Vol 21 (12) ◽  
pp. 4534
Author(s):  
Da Eun Kim ◽  
Bo Yoon Chang ◽  
Byeong Min Jeon ◽  
Jong In Baek ◽  
Sun Chang Kim ◽  
...  
Keyword(s):  
Lipid Metabolism ◽  
Liver Disease ◽  
Fatty Liver ◽  
Nonalcoholic Fatty Liver Disease ◽  
Signaling Pathway ◽  
Hepg2 Cells ◽  
Fatty Liver Disease ◽  
Fatty Acid Synthase ◽  
Density Lipoprotein ◽  
Nonalcoholic Fatty Liver

A ginsenoside F2-enhanced mixture (SGL 121) increases the content of ginsenoside F2 by biotransformation. In the present study, we investigated the effect of SGL 121 on nonalcoholic fatty liver disease (NAFLD) in vitro and in vivo. High-fat, high-carbohydrate-diet (HFHC)-fed mice were administered SGL 121 for 12 weeks to assess its effect on improving NAFLD. In HepG2 cells, SGL 121 acted as an antioxidant, a hepatoprotectant, and had an anti-lipogenic effect. In NAFLD mice, SGL 121 significantly improved body fat mass; levels of hepatic triglyceride (TG), hepatic malondialdehyde (MDA), serum total cholesterol (TC), high-density lipoprotein (HDL), and low-density lipoprotein (LDL); and activities of alanine aminotransferase (ALT) and aspartate aminotransferase (AST). In HepG2 cells, induced by oxidative stress, SGL 121 increased cytoprotection, inhibited reactive oxygen species (ROS) production, and increased antioxidant enzyme activity. SGL 121 activated the Nrf2/HO-1 signaling pathway and improved lipid accumulation induced by free fatty acids (FFA). Sterol regulatory element-binding protein-1 (SREBP-1) and fatty acid synthase (FAS) expression was significantly reduced in NAFLD-induced liver and HepG2 cells treated with SGL 121. Moreover, SGL 121 activated adenosine monophosphate-activated protein kinase (AMPK), which plays an important role in the regulation of lipid metabolism. The effect of SGL 121 on the improvement of NAFLD seems to be related to its antioxidant effects and activation of AMPK. In conclusion, SGL 121 can be potentially used for the treatment of NAFLD.

scholarly journals Inhibiting miR‐27a and miR‐142‐5p attenuate nonalcoholic fatty liver disease by regulating Nrf2 signaling pathway

IUBMB Life ◽  
2019 ◽  
Vol 72 (3) ◽  
pp. 361-372 ◽  
Author(s):  
Maryam Teimouri ◽  
Hossein Hosseini ◽  
Maryam Shabani ◽  
Mehdi Koushki ◽  
Farshid Noorbakhsh ◽  
...  
Keyword(s):  
Liver Disease ◽  
Fatty Liver ◽  
Nonalcoholic Fatty Liver Disease ◽  
Signaling Pathway ◽  
Fatty Liver Disease ◽  
Nonalcoholic Fatty Liver ◽  
Nrf2 Signaling Pathway

scholarly journals Gene Expression and DNA Methylation Alterations in the Glycine N-Methyltransferase Gene in Diet-Induced Nonalcoholic Fatty Liver Disease-Associated Carcinogenesis

2019 ◽  
Vol 170 (2) ◽  
pp. 273-282 ◽  
Author(s):  
Barbara Borowa-Mazgaj ◽  
Aline de Conti ◽  
Volodymyr Tryndyak ◽  
Colleen R Steward ◽  
Leandro Jimenez ◽  
...  
Keyword(s):  
Gene Expression ◽  
Dna Methylation ◽  
Animal Model ◽  
Liver Disease ◽  
Fatty Liver ◽  
Nonalcoholic Fatty Liver Disease ◽  
Fatty Liver Disease ◽  
The United States ◽  
Down Regulation ◽  
Nonalcoholic Fatty Liver

Abstract Nonalcoholic fatty liver disease (NAFLD) is becoming a major etiological risk factor for hepatocellular carcinoma (HCC) in the United States and other Western countries. In this study, we investigated the role of gene-specific promoter cytosine DNA methylation and gene expression alterations in the development of NAFLD-associated HCC in mice using (1) a diet-induced animal model of NAFLD, (2) a Stelic Animal Model of nonalcoholic steatohepatitis-derived HCC, and (3) a choline- and folate-deficient (CFD) diet (CFD model). We found that the development of NAFLD and its progression to HCC was characterized by down-regulation of glycine N-methyltransferase (Gnmt) and this was mediated by progressive Gnmt promoter cytosine DNA hypermethylation. Using a panel of genetically diverse inbred mice, we observed that Gnmt down-regulation was an early event in the pathogenesis of NAFLD and correlated with the extent of the NAFLD-like liver injury. Reduced GNMT expression was also found in human HCC tissue and liver cancer cell lines. In in vitro experiments, we demonstrated that one of the consequences of GNMT inhibition was an increase in genome methylation facilitated by an elevated level of S-adenosyl-L-methionine. Overall, our findings suggest that reduced Gnmt expression caused by promoter hypermethylation is one of the key molecular events in the development of NAFLD-derived HCC and that assessing Gnmt methylation level may be useful for disease stratification.

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