Non-alcoholic fatty liver disease is the most common liver disease in the western world and a risk factor for type 2 diabetes. At present, neither the cause of the disease nor why it progresses in humans is fully understood. Understanding these factors will allow for the development of targeted therapies and prevention strategies.
By Leanne Hodson
Fatty liver disease is a condition in which excess fat accumulates in the liver. Heavy drinking increases the risk, but the fatty deposits can build up even if a person does not drink a lot of alcohol or none at all. In fact, the prevalence of non-alcoholic fatty liver disease (NAFLD) is increasing.
Worldwide, NAFLD is the most common cause of chronic liver disease, including cirrhosis. It also parallels the prevalence of obesity, type 2 diabetes mellitus, and metabolic syndrome, all of which increase the risk of more advanced liver disease. Recent evidence suggests that lifestyle factors, including increased calorie consumption and lack of physical activity or exercise, are key mediators in the accumulation of liver fat. Additionally, several genetic risk factors may predispose to the development and progression of non-alcoholic fatty liver disease.
Studying the disease in vivo is challenging
Various experimental models are used to study the disease, each with their own specific applicability. In a review article recently published in Hormone Molecular Biology and Clinical Investigation, researchers from the Oxford Centre for Diabetes looked at the various ways in which NAFLD can be investigated. These include models in human subjects, models using livers that have been removed from human donors, and cellular based models.
On the whole, the researchers found that studying the disease in human subjects is useful as it allows the study of the disease in its natural state. However, as the liver is difficult to access, the use of such models can be challenging. Nevertheless, the liver can be imaged non-invasively, using techniques such as MRI.
Technological advantages allow to maintain a functioning liver even outside the body – providing the opportunity to study the organ’s metabolism more closely. Cellular models are also important for understanding the mechanisms of NAFLD. However, no single model completely replicates what happens inside a human liver within the body.
When appropriately used, these models will continue to be indispensable tools in NAFLD research. Still, for the future understanding and development of therapies for non-alcoholic fatty liver disease, further development of in vivo, ex situ and in vitro experimental models is required. Ideally, a concerted effort to establish cellular models in vitro that more closely recapitulate the human condition will help clarify the mechanisms underpinning the accumulation of liver fat, and to understand the disease’s pathophysiology and progression.
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Charlotte J. Green, Siôn A. Parry, Pippa J. Gunn, Carlo D.L. Ceresa, Fredrik Rosqvist, Marie-Eve Piché, Leanne Hodson: Studying non-alcoholic fatty liver disease: the ins and outs of in vivo, ex vivo and in vitro human models. 11.08.2018