scholarly journals A Pathophysiological Model of Non-Alcoholic Fatty Liver Disease Using Precision-Cut Liver Slices

Nutrients ◽  
2019 ◽  
Vol 11 (3) ◽  
pp. 507 ◽  
Author(s):  
Grietje Prins ◽  
Theerut Luangmonkong ◽  
Dorenda Oosterhuis ◽  
Henricus Mutsaers ◽  
Frank Dekker ◽  
...  
Keyword(s):  
Metabolic Syndrome ◽  
Liver Disease ◽  
Fatty Liver ◽  
Palmitic Acid ◽  
Fatty Liver Disease ◽  
In Vivo Models ◽  
Alcoholic Fatty Liver ◽  
Liver Slices ◽  
Alcoholic Fatty Liver Disease

Non-alcoholic fatty liver disease (NAFLD) is a common liver disorder closely related to metabolic syndrome. NAFLD can progress to an inflammatory state called non-alcoholic steatohepatitis (NASH), which may result in the development of fibrosis and hepatocellular carcinoma. To develop therapeutic strategies against NAFLD, a better understanding of the molecular mechanism is needed. Current in vitro NAFLD models fail to capture the essential interactions between liver cell types and often do not reflect the pathophysiological status of patients. To overcome limitations of commonly used in vitro and in vivo models, precision-cut liver slices (PCLSs) were used in this study. PCLSs, prepared from liver tissue obtained from male Wistar rats, were cultured in supraphysiological concentrations of glucose, fructose, insulin, and palmitic acid to mimic metabolic syndrome. Accumulation of lipid droplets was visible and measurable after 24 h in PCLSs incubated with glucose, fructose, and insulin, both in the presence and absence of palmitic acid. Upregulation of acetyl-CoA carboxylase 1 and 2, and of sterol responsive element binding protein 1c, suggests increased de novo lipogenesis in PCLSs cultured under these conditions. Additionally, carnitine palmitoyltransferase 1 expression was reduced, which indicates impaired fatty acid transport and disrupted mitochondrial β-oxidation. Thus, steatosis was successfully induced in PCLSs with modified culture medium. This novel ex vivo NAFLD model could be used to investigate the multicellular and molecular mechanisms that drive NAFLD development and progression, and to study potential anti-steatotic drugs.

scholarly journals In Vitro and In Vivo Models of Non-Alcoholic Fatty Liver Disease: A Critical Appraisal

2020 ◽  
Vol 10 (1) ◽  
pp. 36
Author(s):  
Pierre-Antoine Soret ◽  
Julie Magusto ◽  
Chantal Housset ◽  
Jérémie Gautheron
Keyword(s):  
Liver Disease ◽  
Fatty Liver ◽  
Fatty Liver Disease ◽  
Preclinical Research ◽  
In Vivo Models ◽  
Alcoholic Fatty Liver ◽  
Cellular Models ◽  
Alcoholic Fatty Liver Disease

Non-alcoholic fatty liver disease (NAFLD), including non-alcoholic fatty liver (NAFL) and non-alcoholic steatohepatitis (NASH), represents the hepatic manifestation of obesity and metabolic syndrome. Due to the spread of the obesity epidemic, NAFLD is becoming the most common chronic liver disease and one of the principal indications for liver transplantation. However, no pharmacological treatment is currently approved to prevent the outbreak of NASH, which leads to fibrosis and cirrhosis. Preclinical research is required to improve our knowledge of NAFLD physiopathology and to identify new therapeutic targets. In the present review, we summarize advances in NAFLD preclinical models from cellular models, including new bioengineered platforms, to in vivo models, with a particular focus on genetic and dietary mouse models. We aim to discuss the advantages and limits of these different models.

scholarly journals Modeling Non-Alcoholic Fatty Liver Disease (NAFLD) Using “Good-Fit” Genome-Editing Tools

Cells ◽  
2020 ◽  
Vol 9 (12) ◽  
pp. 2572
Author(s):  
Uijin Kim ◽  
Nahyun Kim ◽  
Ha Youn Shin
Keyword(s):  
Liver Disease ◽  
Fatty Liver ◽  
Genome Editing ◽  
Fatty Liver Disease ◽  
Genome Engineering ◽  
In Vivo Models ◽  
Alcoholic Fatty Liver ◽  
Alcoholic Fatty Liver Disease

Non-alcoholic fatty liver disease (NAFLD), which affects both adults and children, is the most common liver disorder worldwide. NAFLD is characterized by excess fat accumulation in the liver in the absence of significant alcohol use. NAFLD is strongly associated with obesity, insulin resistance, metabolic syndrome, as well as specific genetic polymorphisms. Severe NAFLD cases can further progress to cirrhosis, hepatocellular carcinoma (HCC), or cardiovascular complications. Here, we describe the pathophysiological features and critical genetic variants associated with NAFLD. Recent advances in genome-engineering technology have provided a new opportunity to generate in vitro and in vivo models that reflect the genetic abnormalities of NAFLD. We review the currently developed NAFLD models generated using clustered regularly interspaced short palindromic repeats/CRISPR-associated protein 9 (CRISPR/Cas9) genome editing. We further discuss unique features of CRISPR/Cas9 and Cas9 variants, including base editors and prime editor, that are useful for replicating genetic features specific to NAFLD. We also compare advantages and limitations of currently available methods for delivering genome-editing tools necessary for optimal genome editing. This review should provide helpful guidance for selecting “good fit” genome-editing tools and appropriate gene-delivery methods for the successful development of NAFLD models and clinical therapeutics.

Hepatoprotective mechanism of freshwater clam extract alleviates non-alcoholic fatty liver disease: elucidated in vitro and in vivo models

2018 ◽  
Vol 9 (12) ◽  
pp. 6315-6325 ◽  
Author(s):  
Jing-Jen Lin ◽  
Yeuk-Chuen Liu ◽  
Chun-Ju Chang ◽  
Min-Hsiung Pan ◽  
Mong-Fong Lee ◽  
...  
Keyword(s):  
Liver Disease ◽  
Fatty Liver ◽  
Fatty Liver Disease ◽  
In Vivo Models ◽  
Alcoholic Fatty Liver ◽  
Freshwater Clam ◽  
Alcoholic Fatty Liver Disease

In vitro and in vivo hepatoprotective model-verified freshwater clam extract alleviated NAFLD.

scholarly journals Mechanisms of Non-Alcoholic Fatty Liver Disease in the Metabolic Syndrome. A Narrative Review

Antioxidants ◽  
2021 ◽  
Vol 10 (2) ◽  
pp. 270
Author(s):  
Luca Rinaldi ◽  
Pia Clara Pafundi ◽  
Raffaele Galiero ◽  
Alfredo Caturano ◽  
Maria Vittoria Morone ◽  
...  
Keyword(s):  
Metabolic Syndrome ◽  
Risk Factor ◽  
Liver Disease ◽  
Fatty Liver ◽  
Fatty Liver Disease ◽  
Smoking Habit ◽  
Lifestyle Modifications ◽  
Alcoholic Fatty Liver ◽  
The Metabolic Syndrome ◽  
Alcoholic Fatty Liver Disease

Non-alcoholic fatty liver disease (NAFLD) and metabolic syndrome (MS) are two different entities sharing common clinical and physio-pathological features, with insulin resistance (IR) as the most relevant. Large evidence leads to consider it as a risk factor for cardiovascular disease, regardless of age, sex, smoking habit, cholesterolemia, and other elements of MS. Therapeutic strategies remain still unclear, but lifestyle modifications (diet, physical exercise, and weight loss) determine an improvement in IR, MS, and both clinical and histologic liver picture. NAFLD and IR are bidirectionally correlated and, consequently, the development of pre-diabetes and diabetes is the most direct consequence at the extrahepatic level. In turn, type 2 diabetes is a well-known risk factor for multiorgan damage, including an involvement of cardiovascular system, kidney and peripheral nervous system. The increased MS incidence worldwide, above all due to changes in diet and lifestyle, is associated with an equally significant increase in NAFLD, with a subsequent rise in both morbidity and mortality due to both metabolic, hepatic and cardiovascular diseases. Therefore, the slowdown in the increase of the “bad company” constituted by MS and NAFLD, with all the consequent direct and indirect costs, represents one of the main challenges for the National Health Systems.

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