Elafibranor and liraglutide improve differentially liver health and metabolism in a mouse model of non‐alcoholic steatohepatitis

2021 ◽  
Author(s):  
Nikolaos Perakakis ◽  
Konstantinos Stefanakis ◽  
Michael Feigh ◽  
Sanne Skovgard Veidal ◽  
Christos S. Mantzoros
Keyword(s):  
Mouse Model ◽  
Alcoholic Steatohepatitis ◽  
Liver Health

scholarly journals Honokiol Prevents Non-Alcoholic Steatohepatitis-Induced Liver Cancer via EGFR Degradation through the Glucocorticoid Receptor—MIG6 Axis

Cancers ◽  
2021 ◽  
Vol 13 (7) ◽  
pp. 1515
Author(s):  
Keiichiro Okuda ◽  
Atsushi Umemura ◽  
Shiori Umemura ◽  
Seita Kataoka ◽  
Hiroyoshi Taketani ◽  
...  
Keyword(s):  
Mouse Model ◽  
Glucocorticoid Receptor ◽  
Nuclear Translocation ◽  
Growth Factor Receptor ◽  
Public Health Problem ◽  
Egfr Signaling ◽  
Alcoholic Steatohepatitis ◽  
Genetic Mouse Model ◽  
Treatment And Prevention ◽  
Egfr Expression

Non-alcoholic steatohepatitis (NASH) has become a serious public health problem associated with metabolic syndrome. The mechanisms by which NASH induces hepatocellular carcinoma (HCC) remain unknown. There are no approved drugs for treating NASH or preventing NASH-induced HCC. We used a genetic mouse model in which HCC was induced via high-fat diet feeding. This mouse model strongly resembles human NASH-induced HCC. The natural product honokiol (HNK) was tested for its preventative effects against NASH progression to HCC. Then, to clarify the mechanisms underlying HCC development, human HCC cells were treated with HNK. Human clinical specimens were also analyzed to explore this study’s clinical relevance. We found that epidermal growth factor receptor (EGFR) signaling was hyperactivated in the livers of mice with NASH and human HCC specimens. Inhibition of EGFR signaling by HNK drastically attenuated HCC development in the mouse model. Mechanistically, HNK accelerated the nuclear translocation of glucocorticoid receptor (GR) and promoted mitogen-inducible gene 6 (MIG6)/ERBB receptor feedback inhibitor 1 (ERRFI1) expression, leading to EGFR degradation and thereby resulting in robust tumor suppression. In human samples, EGFR-positive HCC tissues and their corresponding non-tumor tissues exhibited decreased ERRFI1 mRNA expression. Additionally, GR-positive non-tumor liver tissues displayed lower EGFR expression. Livers from patients with advanced NASH exhibited decreased ERRFI1 expression. EGFR degradation or inactivation represents a novel approach for NASH–HCC treatment and prevention, and the GR–MIG6 axis is a newly defined target that can be activated by HNK and related compounds.

scholarly journals Gene Expression Analysis of the Activating Factor 3/Nuclear Protein 1 Axis in a Non-alcoholic Steatohepatitis Mouse Model

2019 ◽  
Vol 62 (1) ◽  
pp. 036-046 ◽  
Author(s):  
Ran Nagahara ◽  
Tomomitsu Matono ◽  
Takaaki Sugihara ◽  
Yukako Matsuki ◽  
Masafumi Yamane ◽  
...  
Keyword(s):  
Gene Expression ◽  
Mouse Model ◽  
Expression Analysis ◽  
Gene Expression Analysis ◽  
Nuclear Protein ◽  
Alcoholic Steatohepatitis

scholarly journals Antifibrotic effects of ambrisentan, an endothelin-A receptor antagonist, in a non-alcoholic steatohepatitis mouse model

2016 ◽  
Vol 8 (22) ◽  
pp. 933 ◽  
Author(s):  
Toshiaki Okamoto ◽  
Masahiko Koda ◽  
Kennichi Miyoshi ◽  
Takumi Onoyama ◽  
Manabu Kishina ◽  
...  
Keyword(s):  
Mouse Model ◽  
Receptor Antagonist ◽  
Alcoholic Steatohepatitis ◽  
Endothelin A Receptor ◽  
Endothelin A

scholarly journals Rosiglitazone improves characteristics of Non‐Alcoholic Steatohepatitis (NASH) in a mouse model of metabolic syndrome

2010 ◽  
Vol 24 (S1) ◽  
Author(s):  
Anisha A. Gupte ◽  
Joey Z. Liu ◽  
Laurie J. Minze ◽  
Yuelan Ren ◽  
Jessica R. Wiles ◽  
...  
Keyword(s):  
Metabolic Syndrome ◽  
Mouse Model ◽  
Alcoholic Steatohepatitis

scholarly journals Towards a standard diet-induced and biopsy-confirmed mouse model of non-alcoholic steatohepatitis: Impact of dietary fat source

2019 ◽  
Vol 25 (33) ◽  
pp. 4904-4920 ◽  
Author(s):  
Michelle L Boland ◽  
Denise Oró ◽  
Kirstine S Tølbøl ◽  
Sebastian T Thrane ◽  
Jens Christian Nielsen ◽  
...  
Keyword(s):  
Mouse Model ◽  
Dietary Fat ◽  
Standard Diet ◽  
Alcoholic Steatohepatitis

A novel mouse model of non-alcoholic steatohepatitis suggests that liver fibrosis initiates around lipid-laden macrophages

2021 ◽  
Author(s):  
Mayuko Ichimura-Shimizu ◽  
Yosuke Tsuchiyama ◽  
Yuki Morimoto ◽  
Minoru Matsumoto ◽  
Tomoko Kobayashi ◽  
...  
Keyword(s):  
Liver Fibrosis ◽  
Mouse Model ◽  
Alcoholic Steatohepatitis

scholarly journals Periostin antisense oligonucleotide prevents hepatic steatosis and fibrosis in a mouse model of non‐alcoholic steatohepatitis

2020 ◽  
Vol 35 (12) ◽  
pp. 2140-2150 ◽  
Author(s):  
Tomoki Kobayashi ◽  
Keishi Kanno ◽  
Phuong Thao Nguyen ◽  
Akiko Sugiyama ◽  
Akihiro Kawahara ◽  
...  
Keyword(s):  
Mouse Model ◽  
Hepatic Steatosis ◽  
Antisense Oligonucleotide ◽  
Alcoholic Steatohepatitis
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