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

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.

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

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.

A 3-week nonalcoholic steatohepatitis mouse model allows the rapid evaluation of liraglutide and elafibranor benefits on NASH

Metabolism ◽  
2020 ◽  
Vol 104 ◽  
pp. 154113
Author(s):  
François Briand ◽  
Thibaut Duparc ◽  
Christophe Heymes ◽  
Lucile Bonada ◽  
Rémy Burcelin ◽  
...  
Keyword(s):  
Mouse Model ◽  
Nonalcoholic Steatohepatitis ◽  
Rapid Evaluation

scholarly journals Sugar Kelp (Saccharina latissima) Inhibits Hepatic Inflammation and Fibrosis with Increased Metabolic Rates in a Mouse Model of Diet-induced Nonalcoholic Steatohepatitis (OR24-08-19)

2019 ◽  
Vol 3 (Supplement_1) ◽  
Author(s):  
Mi-Bo Kim ◽  
Yoojin Lee ◽  
Minkyung Bae ◽  
Hyunju Kang ◽  
Siqi Hu ◽  
...  
Keyword(s):  
Physical Activity ◽  
Liver Fibrosis ◽  
Energy Expenditure ◽  
Mouse Model ◽  
Total Cholesterol ◽  
Nonalcoholic Steatohepatitis ◽  
Metabolic Rates ◽  
Metabolic Disturbances ◽  
Macrophage Marker ◽  
M1 Macrophage

Abstract Objectives We investigated whether consumption of sugar kelp, an edible brown seaweed, can attenuate metabolic disturbances and nonalcoholic steatohepatitis (NASH) in a mouse model of NASH with evident liver fibrosis. Methods Male C57BL/6 J mice were fed a low-fat control (LF; 6% fat by wt), a high-fat/high-sucrose/high-cholesterol control (HF; 34% fat, 34% sucrose, 2.0% cholesterol by wt), or a HF containing sugar kelp (HF-Kelp; 6.0% dried sugar kelp powder by wt) for 14 weeks. Blood chemistry as well as biochemical, molecular, and histological analyses were conducted in the liver and epididymal white adipose tissue (eWAT). Metabolic rates, energy expenditure, and physical activity of mice were determined using indirect calorimetry Results Body weight of mice fed HF-Kelp was significantly lower than that of HF group. Compared to LF, HF significantly increased serum total cholesterol and glucose, which were decreased by kelp. In the liver, HF-Kelp group showed decreases in weight, triglycerides, total cholesterol, and steatosis compared with HF-fed mice. Also, kelp decreased hepatic expression of a macrophage marker F4/80 and an M1 macrophage marker CD11c. Mice fed HF-Kelp also exhibited decreased liver fibrosis as evidenced by less expression of fibrogenic genes and collagen accumulation than those of HF group. In eWAT, HF-Kelp diet reduced weight and adipocyte size compared with HF control. While HF-Kelp diet increased mRNA abundance of peroxisome proliferator activated receptor γ, it decreased the expression of collagen type VI alpha 1 chain, F4/80, CD11c, and tumor necrosis factor α, in eWAT. Oxygen consumption, carbon dioxide production, energy expenditure, and physical activity were significantly higher in HF-Kelp group than HF. Conclusions Kelp consumption markedly prevented weight gain, fat accumulation, inflammation, and fibrosis in the liver and eWAT of mice with NASH. The health benefits of kelp were accompanied by increased metabolic rates, energy expenditure, and physical activity. Therefore, kelp may be consumed to prevent obesity-associated metabolic disturbances and NASH. Funding Sources This study was supported by USDA Hatch.

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