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 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.

scholarly journals Naringin protects against non-alcoholic fatty liver disease by promoting autophagic flux and lipophagy

2021 ◽  
Author(s):  
Lingling Guan ◽  
Lan Guo ◽  
Heng Zhang ◽  
Hao Liu ◽  
Yuan Qiao ◽  
...  
Keyword(s):  
Liver Disease ◽  
Fatty Liver ◽  
Hepatic Steatosis ◽  
Fatty Liver Disease ◽  
Autophagic Flux ◽  
Mechanism Study ◽  
Alcoholic Fatty Liver ◽  
Alcoholic Fatty Liver Disease

Abstract Background and Purpose: The autophagic degradation of lipid droplets (LDs), termed lipophagy, is the main mechanism contributing to lipid consumption in hepatocytes. The identification of effective and safe natural compounds that target lipophagy to eliminate excess lipids may be a potential therapeutic strategy for non-alcoholic fatty liver disease (NAFLD). Here, we investigated the effects of naringin on NAFLD and the underlying mechanism. Experimental Approach: The role of naringin was investigated in mice fed a high-fat diet (HFD) to induce NAFLD, as well as in AML12 cells and primary hepatocytes stimulated by palmitate (PA). Transcription factor EB (TFEB)-knockdown AML12 cells and hepatocyte-specific TFEB-knockout mice were also used for the mechanism study. In vivo and in vitro studies were conducted using transmission electron microscopy, immunofluorescence techniques and western blot analysis. Key Results: We found that naringin treatment effectively relieved HFD-induced hepatic steatosis in mice and inhibited palmitate (PA)-induced lipid accumulation in hepatocytes. The increased p62 and LC3-II levels observed with excess lipid-support autophagosome accumulation and impaired autophagic flux. Treatment with naringin restored TFEB-mediated lysosomal biogenesis, thereby promoting the fusion of autophagosomes and lysosomes, restoring impaired autophagic flux and further inducing lipophagy. However, the knockdown of TFEB in hepatocytes or the hepatocyte-specific knockout of TFEB in mice abrogated naringin-induced lipophagy, which eliminated the therapeutic effect of naringin on hepatic steatosis. Conclusion and Implications: These results demonstrate that TFEB-mediated lysosomal biogenesis and subsequent lipophagy play essential roles in the ability of naringin to mitigate hepatic steatosis and suggest that naringin is a promising drug for treating or relieving NAFLD.

scholarly journals Blueberry, combined with probiotics, alleviates non-alcoholic fatty liver diseaseviaIL-22-mediated JAK1/STAT3/BAX signaling

2018 ◽  
Vol 9 (12) ◽  
pp. 6298-6306 ◽  
Author(s):  
Juanjuan Zhu ◽  
Mingyu Zhou ◽  
Xueke Zhao ◽  
Mao Mu ◽  
Mingliang Cheng
Keyword(s):  
Liver Disease ◽  
Fatty Liver ◽  
Fatty Liver Disease ◽  
Alcoholic Fatty Liver ◽  
Alcoholic Fatty Liver Disease

Blueberry, combined with probiotics, improves non-alcoholic fatty liver disease bothin vivoandin vitroby IL-22.

scholarly journals Studying non-alcoholic fatty liver disease: the ins and outs of in vivo, ex vivo and in vitro human models

2018 ◽  
Vol 0 (0) ◽  
Author(s):  
Charlotte J. Green ◽  
Siôn A. Parry ◽  
Pippa J. Gunn ◽  
Carlo D.L. Ceresa ◽  
Fredrik Rosqvist ◽  
...  
Keyword(s):  
Liver Disease ◽  
Fatty Liver ◽  
Fatty Liver Disease ◽  
In Vitro Models ◽  
Ex Situ ◽  
Whole Body ◽  
Alcoholic Fatty Liver ◽  
Alcoholic Fatty Liver Disease

AbstractThe prevalence of non-alcoholic fatty liver disease (NAFLD) is increasing. Determining the pathogenesis and pathophysiology of human NAFLD will allow for evidence-based prevention strategies, and more targeted mechanistic investigations. Various in vivo, ex situ and in vitro models may be utilised to study NAFLD; but all come with their own specific caveats. Here, we review the human-based models and discuss their advantages and limitations in regards to studying the development and progression of NAFLD. Overall, in vivo whole-body human studies are advantageous in that they allow for investigation within the physiological setting, however, limited accessibility to the liver makes direct investigations challenging. Non-invasive imaging techniques are able to somewhat overcome this challenge, whilst the use of stable-isotope tracers enables mechanistic insight to be obtained. Recent technological advances (i.e. normothermic machine perfusion) have opened new opportunities to investigate whole-organ metabolism, thus ex situ livers can be investigated directly. Therefore, investigations that cannot be performed in vivo in humans have the potential to be undertaken. In vitro models offer the ability to perform investigations at a cellular level, aiding in elucidating the molecular mechanisms of NAFLD. However, a number of current models do not closely resemble the human condition and work is ongoing to optimise culturing parameters in order to recapitulate this. In summary, no single model currently provides insight into the development, pathophysiology and progression across the NAFLD spectrum, each experimental model has limitations, which need to be taken into consideration to ensure appropriate conclusions and extrapolation of findings are made.

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