Nonalcoholic Steatohepatitis (NASH): From Molecular Mechanisms to Therapeutic Opportunities

A special issue of Cells (ISSN 2073-4409). This special issue belongs to the section "Cellular Pathology".

Deadline for manuscript submissions: closed (31 January 2024) | Viewed by 3110

Special Issue Editor


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Guest Editor
Gastroenterology and Hepatology, Medical College of Wisconsin, Milwaukee, WI 53226, USA
Interests: cirrhosis; liver disease; portal hypertension; viral hepatitis; end-stage liver disease; chronic liver disease; non-alcoholic liver disease; liver failure

Special Issue Information

Dear Colleagues, 

Nonalcoholic fatty liver disease (NAFLD), along with its progressive form of disease the nonalcoholic Steatohepatitis (NASH), is the most common chronic liver disease in the Western world. The prevalence of this disease is rapidly increasing in the rest of the world population. Despite increasing awareness and research in mitigating the disease, readily available diagnostic biomarkers and definitive pharmacological therapy are unavailable. This could become an increasing concern as the prevalence of this disease grows in the population, especially in certain parts, such as the USA, where more than 50% have fatty liver disease. In this regard, a deeper understanding of the molecular mechanisms of the disease process will guide us to serve the community at large. 

The emphasis of this Special Issue is on the recent understanding and advances in the pathophysiology of NAFLD and NASH progression, genomics in NASH, the role of adaptive immunity in NASH, the molecular and cellular mechanisms of fibrosis in NASH, omics and biomarkers, the gut microbiome in NAFLD, the consideration of unique populations, including NASH in the pediatric population and lean NASH, available pharmacological agents and phase 3 drugs for management, and possible new interventions (phase 2 trial drugs) based on treatment targets. 

I look forward to receiving your contributions and compiling this exciting Special Issue. 

Dr. Achuthan Sourianarayanane
Guest Editor

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Published Papers (2 papers)

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21 pages, 3987 KiB  
Article
Concentration-Dependent Attenuation of Pro-Fibrotic Responses after Cannabigerol Exposure in Primary Rat Hepatocytes Cultured in Palmitate and Fructose Media
by Klaudia Sztolsztener, Karolina Konstantynowicz-Nowicka, Anna Pędzińska-Betiuk and Adrian Chabowski
Cells 2023, 12(18), 2243; https://doi.org/10.3390/cells12182243 - 9 Sep 2023
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Abstract
Hepatic fibrosis is a consequence of liver injuries, in which the overproduction and progressive accumulation of extracellular matrix (ECM) components with the simultaneous failure of matrix turnover mechanisms are observed. The aim of this study was to investigate the concentration-dependent influence of cannabigerol [...] Read more.
Hepatic fibrosis is a consequence of liver injuries, in which the overproduction and progressive accumulation of extracellular matrix (ECM) components with the simultaneous failure of matrix turnover mechanisms are observed. The aim of this study was to investigate the concentration-dependent influence of cannabigerol (CBG, Cannabis sativa L. component) on ECM composition with respect to transforming growth factor beta 1 (TGF-β1) changes in primary hepatocytes with fibrotic changes induced by palmitate and fructose media. Cells were isolated from male Wistar rats’ livers in accordance with the two-step collagenase perfusion technique. This was followed by hepatocytes incubation with the presence or absence of palmitate with fructose and/or cannabigerol (at concentrations of 1, 5, 10, 15, 25, 30 µM) for 48 h. The expression of ECM mRNA genes and proteins was determined using PCR and Western blot, respectively, whereas media ECM level was evaluated using ELISA. Our results indicated that selected low concentrations of CBG caused a reduction in TGF-β1 mRNA expression and secretion into media. Hepatocyte exposure to cannabigerol at low concentrations attenuated collagen 1 and 3 deposition. The protein and/or mRNA expressions and MMP-2 and MMP-9 secretion were augmented using CBG. Considering the mentioned results, low concentrations of cannabigerol treatment might expedite fibrosis regression and promote regeneration. Full article
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Review
Thyroid Hormone and Mitochondrial Dysfunction: Therapeutic Implications for Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD)
by Raghu Ramanathan, Sohum A. Patwa, Ahmad Hassan Ali and Jamal A. Ibdah
Cells 2023, 12(24), 2806; https://doi.org/10.3390/cells12242806 - 9 Dec 2023
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Abstract
Metabolic dysfunction-associated steatotic liver disease (MASLD), formerly termed nonalcoholic fatty liver disease (NAFLD), is a widespread global health concern that affects around 25% of the global population. Its influence is expanding, and it is anticipated to overtake alcohol as the leading cause of [...] Read more.
Metabolic dysfunction-associated steatotic liver disease (MASLD), formerly termed nonalcoholic fatty liver disease (NAFLD), is a widespread global health concern that affects around 25% of the global population. Its influence is expanding, and it is anticipated to overtake alcohol as the leading cause of liver failure and liver-related death worldwide. Unfortunately, there are no approved therapies for MASLD; as such, national and international regulatory health agencies undertook strategies and action plans designed to expedite the development of drugs for treatment of MASLD. A sedentary lifestyle and an unhealthy diet intake are important risk factors. Western countries have a greater estimated prevalence of MASLD partly due to lifestyle habits. Mitochondrial dysfunction is strongly linked to the development of MASLD. Further, it has been speculated that mitophagy, a type of mitochondrial quality control, may be impaired in MASLD. Thyroid hormone (TH) coordinates signals from the nuclear and mitochondrial genomes to control mitochondrial biogenesis and function in hepatocytes. Mitochondria are known TH targets, and preclinical and clinical studies suggest that TH, thyroid receptor β (TR-β) analogs, and synthetic analogs specific to the liver could be of therapeutic benefit in treating MASLD. In this review, we highlight how mitochondrial dysfunction contributes to development of MASLD, and how understanding the role of TH in improving mitochondrial function paved the way for innovative drug development programs of TH-based therapies targeting MASLD. Full article
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