scholarly journals Attenuated Ochratoxin A Transporter Expression in a Mouse Model of Nonalcoholic Steatohepatitis Protects against Proximal Convoluted Tubule Toxicity.

2021 ◽  
pp. DMD-MR-2021-000451
Author(s):  
Joseph L. Jilek ◽  
Kayla L. FROST ◽  
Solène MARIE ◽  
Cassandra M. MYERS ◽  
Michael GOEDKEN ◽  
...  
Keyword(s):  
Mouse Model ◽  
Ochratoxin A ◽  
Nonalcoholic Steatohepatitis ◽  
Proximal Convoluted Tubule ◽  
Transporter Expression

scholarly journals Berberine Prevents Disease Progression of Nonalcoholic Steatohepatitis through Modulating Multiple Pathways

Cells ◽  
2021 ◽  
Vol 10 (2) ◽  
pp. 210
Author(s):  
Yanyan Wang ◽  
Yun-Ling Tai ◽  
Derrick Zhao ◽  
Yuan Zhang ◽  
Junkai Yan ◽  
...  
Keyword(s):  
Bile Acid ◽  
Mouse Model ◽  
Disease Progression ◽  
Nonalcoholic Steatohepatitis ◽  
Noncoding Rna ◽  
Metabolic Diseases ◽  
Immune Cell ◽  
Stellate Cell ◽  
Clinical Investigation ◽  
Beneficial Effects

Background and Aims: The disease progression of nonalcoholic fatty liver disease (NAFLD) from simple steatosis (NAFL) to nonalcoholic steatohepatitis (NASH) is driven by multiple factors. Berberine (BBR) is an ancient Chinese medicine and has various beneficial effects on metabolic diseases, including NAFLD/NASH. However, the underlying mechanisms remain incompletely understood due to the limitation of the NASH animal models used. Methods: A high-fat and high-fructose diet-induced mouse model of NAFLD, the best available preclinical NASH mouse model, was used. RNAseq, histological, and metabolic pathway analyses were used to identify the potential signaling pathways modulated by BBR. LC–MS was used to measure bile acid levels in the serum and liver. The real-time RT-PCR and Western blot analysis were used to validate the RNAseq data. Results: BBR not only significantly reduced hepatic lipid accumulation by modulating fatty acid synthesis and metabolism but also restored the bile acid homeostasis by targeting multiple pathways. In addition, BBR markedly inhibited inflammation by reducing immune cell infiltration and inhibition of neutrophil activation and inflammatory gene expression. Furthermore, BBR was able to inhibit hepatic fibrosis by modulating the expression of multiple genes involved in hepatic stellate cell activation and cholangiocyte proliferation. Consistent with our previous findings, BBR’s beneficial effects are linked with the downregulation of microRNA34a and long noncoding RNA H19, which are two important players in promoting NASH progression and liver fibrosis. Conclusion: BBR is a promising therapeutic agent for NASH by targeting multiple pathways. These results provide a strong foundation for a future clinical investigation.

scholarly journals Modeling Human Nonalcoholic Steatohepatitis-Associated Changes in Drug Transporter Expression Using Experimental Rodent Models

2014 ◽  
Vol 42 (4) ◽  
pp. 586-595 ◽  
Author(s):  
Mark J. Canet ◽  
Rhiannon N. Hardwick ◽  
April D. Lake ◽  
Anika L. Dzierlenga ◽  
John D. Clarke ◽  
...  
Keyword(s):  
Nonalcoholic Steatohepatitis ◽  
Rodent Models ◽  
Drug Transporter ◽  
Transporter Expression

scholarly journals Resveratrol ameliorates fibrosis and inflammation in a mouse model of nonalcoholic steatohepatitis

2016 ◽  
Vol 6 (1) ◽  
Author(s):  
Takaomi Kessoku ◽  
Kento Imajo ◽  
Yasushi Honda ◽  
Takayuki Kato ◽  
Yuji Ogawa ◽  
...  
Keyword(s):  
Mouse Model ◽  
Nonalcoholic Steatohepatitis

GH and IGF-I Ameliorate Liver Steatosis and Fibrosis in Nonalcoholic Steatohepatitis Mouse Model

2011 ◽  
pp. P1-139-P1-139
Author(s):  
Hitoshi Nishizawa ◽  
Genzo Iguchi ◽  
Michiko Takahashi ◽  
Masaaki Yamamoto ◽  
Kentaro Suda ◽  
...  
Keyword(s):  
Mouse Model ◽  
Nonalcoholic Steatohepatitis ◽  
Liver Steatosis ◽  
Igf I

scholarly journals Renal Transporter Expression Changes in Rodent Models of Nonalcoholic Steatohepatitis

2021 ◽  
Vol 35 (S1) ◽  
Author(s):  
Kayla Frost ◽  
Joseph Jilek ◽  
Erica Toth ◽  
Michael Goedken ◽  
Nathan Cherrington
Keyword(s):  
Nonalcoholic Steatohepatitis ◽  
Rodent Models ◽  
Renal Transporter ◽  
Transporter Expression

1258 ORAL BIFIDOBACTERIUM ADOLESCENTIS SUPPLEMENTATION ATTENUATES NONALCOHOLIC STEATOHEPATITIS (NASH) IN A MOUSE MODEL

2012 ◽  
Vol 56 ◽  
pp. S497-S498
Author(s):  
A. Reichold ◽  
S. Brenner ◽  
A. Spruss ◽  
A. Rings ◽  
K. Förster-Fromme ◽  
...  
Keyword(s):  
Mouse Model ◽  
Nonalcoholic Steatohepatitis ◽  
Bifidobacterium Adolescentis

scholarly journals Liraglutide improves hepatic steatosis and metabolic dysfunctions in a 3-week dietary mouse model of nonalcoholic steatohepatitis

2019 ◽  
Vol 317 (4) ◽  
pp. G508-G517
Author(s):  
Thibaut Duparc ◽  
François Briand ◽  
Charlotte Trenteseaux ◽  
Jules Merian ◽  
Guillaume Combes ◽  
...  
Keyword(s):  
Drinking Water ◽  
Mouse Model ◽  
Hepatic Steatosis ◽  
Cholic Acid ◽  
Nonalcoholic Steatohepatitis ◽  
Dietary Intervention ◽  
Liver Steatosis ◽  
Rapid Screening ◽  
Drug Candidates ◽  
Stress Markers

Nonalcoholic steatohepatitis (NASH) is an emerging health problem worldwide. However, efficacious pharmacological treatment for NASH is lacking. A major issue for preclinical evaluation of potential therapeutics for NASH is the limited number of appropriate animal models, i.e., models that do not require long-term dietary intervention and adequately mimic disease progression in humans. The present study aimed to evaluate a 3-wk dietary mouse model of NASH and validate it by studying the effects of liraglutide, a compound in advanced clinical development for NASH. C57BL6/J mice were fed a diet high in fat (60%), cholesterol (1.25%), and cholic acid (0.5%), along with 2% hydroxypropyl-β-cyclodextrin in drinking water (HFCC-CDX diet). Histological and biological parameters were measured at 1 and 3 wk. After 1-wk diet induction, liraglutide was administrated daily for 2 wk and then NASH-associated phenotypic aspects were evaluated in comparison with control mice. Prior to treatment with liraglutide, mice fed the HFCC-CDX diet for 1 wk developed liver steatosis and had increased levels of oxidative-stress markers and hepatic and systemic inflammation. For mice not treated with liraglutide, these aspects were even more pronounced after 3 wk of the dietary period, with additional liver insulin resistance and fibrosis. Liraglutide treatment corrected the diet-induced alterations in glucose metabolism and significantly reduced hepatic steatosis and inflammation. This study provides a novel 3-wk dietary model of mice that rapidly develop NASH features, and this model will be suitable for evaluating the therapeutic efficacy of compounds in preclinical drug development for NASH. NEW & NOTEWORTHY We propose a diet high in fat (60%), cholesterol (1.25%), and cholic acid (0.5%) along with 2% hydroxypropyl-β-cyclodextrin in drinking water (HFCC-CDX diet) as a new dietary model of nonalcoholic steatohepatitis. We used the HFCC-CDX model to reproduce the main features of disease development in humans for the purpose of facilitating the rapid screening of drug candidates and prioritizing the more promising candidates for advanced preclinical assessment and subsequent clinical trials.

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