scholarly journals A Novel GLP-1 and FGF21 Dual Agonist Has Therapeutic Potential for Diabetes and Non-Alcoholic Steatohepatitis

2020 ◽  
Author(s):  
Qi Pan ◽  
Shushan Lin ◽  
Yu Li ◽  
Liang Liu ◽  
Xiaoping Li ◽  
...  
Keyword(s):  
Therapeutic Potential ◽  
Alcoholic Steatohepatitis ◽  
Dual Agonist

Exploring the therapeutic potential of Glucagon/GLP-1 dual agonist ZP2929 in a mouse model of diet induced and biopsy-confirmed non-alcoholic steatohepatitis

2017 ◽  
Vol 66 (1) ◽  
pp. S102
Author(s):  
J. Skarbaliene ◽  
A.N. Madsen ◽  
U. Mouritzen ◽  
H.H. Bak ◽  
R. Just
Keyword(s):  
Mouse Model ◽  
Therapeutic Potential ◽  
Alcoholic Steatohepatitis ◽  
Dual Agonist

Stable analogues of the dual agonist dogfish glucagon show better therapeutic potential than exendin-4 in diet induced obese diabetic mice

2015 ◽  
Author(s):  
Finbarr P M O'Harte ◽  
Ming T Ng ◽  
J Michael Conlon ◽  
Peter R Flatt
Keyword(s):  
Therapeutic Potential ◽  
Diabetic Mice ◽  
Dual Agonist

Therapeutic potential of curcumin in non-alcoholic steatohepatitis

2005 ◽  
Vol 18 (2) ◽  
pp. 212-221 ◽  
Author(s):  
Haim Shapiro ◽  
Rafael Bruck
Keyword(s):  
Insulin Resistance ◽  
Hepatic Steatosis ◽  
Animal Studies ◽  
Cell Activation ◽  
Therapeutic Potential ◽  
Stellate Cell ◽  
Indirect Evidence ◽  
Deficient Diet ◽  
Alcoholic Steatohepatitis ◽  
Ppar Γ

Non-alcoholic steatohepatitis (NASH) may be associated with a number of clinical conditions, but it occurs most commonly in patients with insulin resistance. There is as yet no established disease-modifying treatment, and a safe and broadly available agent that targets hepatic steatosis, insulin resistance, inflammation and fibrosis is necessary. The polyphenolic compound curcumin exhibits antioxidant and anti-inflammatory properties, inhibits NF-κB and activates PPAR-γ. In rodents, curcumin prevents dietary-induced hepatic steatosis, hepatic stellate cell activation and production of fibrotic proteins, and ameliorates steatohepatitis induced by the intake of alcohol or a methionine–choline-deficient diet. Indirect evidence suggests that curcumin may improve insulin sensitivity in diabetes and inflammatory states. The present paper reviews the numerous cellular and animal studies indicating that curcumin attenuates many of the pathophysiological processes involved in the development and progression of NASH. It is suggested that basic and clinical studies on curcumin in the development and progression of NASH are indicated.

scholarly journals A 3D primary human cell-based in vitro model of non-alcoholic steatohepatitis for efficacy testing of clinical drug candidates

2021 ◽  
Author(s):  
Simon Ströbel ◽  
Radina Kostadinova ◽  
Katia Fiaschetti-Egli ◽  
Jana Rupp ◽  
Manuela Bieri ◽  
...  
Keyword(s):  
Complex Disease ◽  
Therapeutic Potential ◽  
Expression Patterns ◽  
Therapeutic Interventions ◽  
Type I ◽  
Drug Candidates ◽  
Procollagen Type ◽  
Alcoholic Steatohepatitis ◽  
Inflammatory Stimuli

Abstract Non-alcoholic steatohepatitis (NASH) is a progressive and severe liver disease, characterized by lipid accumulation, inflammation, and downstream fibrosis. Despite its increasing prevalence, there is no approved treatment yet available for patients. This has been at least partially due to the lack of predictive preclinical models for studying this complex disease. Here, we present a 3D in vitro microtissue model that uses spheroidal, scaffold free co-culture of primary human hepatocytes, Kupffer cells, liver endothelial cells and hepatic stellate cells. Upon exposure to defined and clinically relevant lipotoxic and inflammatory stimuli, these microtissues develop key pathophysiological features of NASH within 10 days, including an increase of intracellular triglyceride content and lipids, and release of pro-inflammatory cytokines. Furthermore, fibrosis was evident through release of procollagen type I, and increased deposition of extracellular collagen fibers. Whole transcriptome analysis revealed changes in the regulation of pathways associated with NASH, such as lipid metabolism, inflammation and collagen processing. Importantly, treatment with anti-NASH drug candidates (Selonsertib and Firsocostat) decreased the measured specific disease parameter, in accordance with clinical observations. These drug treatments also significantly changed the gene expression patterns of the microtissues, thus providing mechanisms of action and revealing therapeutic potential. In summary, this human NASH model represents a promising drug discovery tool for understanding the underlying complex mechanisms in NASH, evaluating efficacy of anti-NASH drug candidates and identifying new approaches for therapeutic interventions.

scholarly journals Discovery of lipotoxicity-sensitive transcription factors in non-alcoholic steatohepatitis

2021 ◽  
Author(s):  
Joaquín Pérez-Schindler ◽  
Elyzabeth Vargas-Fernández ◽  
Bettina Karrer-Cardel ◽  
Danilo Ritz ◽  
Alexander Schmidt ◽  
...  
Keyword(s):  
Transcription Factors ◽  
Molecular Mechanisms ◽  
Therapeutic Potential ◽  
Chromatin Accessibility ◽  
Alcoholic Fatty Liver ◽  
Mouse Hepatocyte ◽  
Alcoholic Steatohepatitis ◽  
Pathogenic Factors ◽  
Mouse Hepatocytes ◽  
Regulated Gene Expression

Non-alcoholic fatty liver disease is continuum of disorders among which non-alcoholic steatohepatitis (NASH) is particularly associated with a negative prognosis. Hepatocyte lipotoxicity is one of the main pathogenic factors of liver fibrosis and NASH. However, the molecular mechanisms regulating this process are poorly understood. Here, we integrated transcriptomic and chromatin accessibility analyses from human liver and mouse hepatocytes to identify lipotoxicity-sensitive transcription factors. We found that the transcription factors MAFK and TCF4 were activated in liver from NASH patients and by mouse hepatocyte lipotoxicity. Genetic deletion of these transcription factors protected hepatocytes against saturated fatty acid oversupply. Notably, MAFK- and TCF4-regulated gene expression linked to lipotoxicity closely correlated with transcriptional patters in fibrosis progression in NASH patients. Collectively, our findings uncovered novel molecular insights into lipotoxicity-induced NASH, revealing the relevance and therapeutic potential of MAFK and TCF4 in human disease.

scholarly journals Therapeutic Potential of Peroxisome Proliferators–Activated Receptor-α/γ Dual Agonist With Alleviation of Endoplasmic Reticulum Stress for the Treatment of Diabetes

Diabetes ◽  
2007 ◽  
Vol 57 (3) ◽  
pp. 737-745 ◽  
Author(s):  
Kyu Lee Han ◽  
Joo Sun Choi ◽  
Jae Young Lee ◽  
Jihyun Song ◽  
Myung Kuk Joe ◽  
...  
Keyword(s):  
Endoplasmic Reticulum ◽  
Endoplasmic Reticulum Stress ◽  
Therapeutic Potential ◽  
Peroxisome Proliferators ◽  
Treatment Of Diabetes ◽  
Dual Agonist

Evaluation of the therapeutic potential effect of Fas receptor gene knockdown in experimental model of non-alcoholic steatohepatitis

2019 ◽  
Vol 53 (5) ◽  
pp. 486-496 ◽  
Author(s):  
Feryal Savari ◽  
Mohammad Badavi ◽  
Anahita Rezaie ◽  
Mohammad Kazem Gharib-Naseri ◽  
Seyyed Ali Mard
Keyword(s):  
Experimental Model ◽  
Therapeutic Potential ◽  
Receptor Gene ◽  
Potential Effect ◽  
Gene Knockdown ◽  
Fas Receptor ◽  
Alcoholic Steatohepatitis

A GLP‐1/GLP‐2 receptor dual agonist to treat non‐alcoholic steatohepatitis: targeting the gut‐liver axis and microbiome.

Hepatology ◽  
2021 ◽  
Author(s):  
Eun Ran Kim ◽  
Jeong Su Park ◽  
Jin Hee Kim ◽  
Ji Young Oh ◽  
In Jeong Oh ◽  
...  
Keyword(s):  
Alcoholic Steatohepatitis ◽  
Dual Agonist
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