According to a study in The Lancet, global obesity is expected to reach 18 percent among men and 21 percent among women¹. However, as the proportion of obese increases, so does the proportion of those who may suffer from fatty liver disease². As a result of a sedentary lifestyle and a diet too rich in fat, it is estimated that around 30 percent of the population already has a fatty liver³. Conditions such as obesity and type 2 diabetes can increase patients' risk of developing NAFLD. In serious cases, this leads to a severe form known as non-alcoholic steatohepatitis (NASH). This can result in liver cirrhosis, liver cancer, or, in the final stages, liver failure.

To study NAFLD and NASH, animal models (4), as well as cell culture models (disease-on-a-disease), are used. However, due to the differences in disease phenotypes between humans and animals, research results from animals cannot be reliably extrapolated to the human situation.

To simulate key metabolic features in NAFLD, researchers from the NanoScience Technology Center at the University of Central Florida (UCF), in collaboration with the company Hesperos Inc. have now designed a two-chamber system that combines functional human liver cells and fat cells in a microfluidic recirculating serum-free medium. According to lead developer Prof. James J. Hickman, Ph. D., there is now a first human-based multi-chamber system that can be used to model a NAFLD phenotype with adipocytes.

Study results have shown that the model can accurately replicate important pathological features that are consistent with the findings of other researchers and physicians. For example, the team was able to show that proinflammatory TNF-α significantly increases steatosis in the co-culture of liver and fat cells. This was not the case without the fat cells. Moreover, the CYP3A4 activity was decreased in the liver cells. The liver enzyme metabolizes approximately 40 percent of all drugs and accounts for the majority of CYP enzymes in the liver⁵. In the case of metformin, an anti-diabetic drug that had been shown to be unsuitable in NAFLD, the team was able to demonstrate that the drug significantly reduced steatosis, but only at significantly higher doses,  which humans are not normally exposed to. 

Original paper:
Victoria L. Slaughter, John W. Rumsey, Rachel Boone, Duaa Malik, Yunqing Cai, Narasimhan Narasimhan Sriram, Christopher J. Long, Christopher W. McAleer, Stephen Lambert, Michael L. Shuler & J. J. Hickman (2021). Validation of an adipose‑liver human‑on‑a‑chip model of NAFLD for preclinical therapeutic efficacy evaluation. Scientific Reports 11: 13159. https://doi.org/10.1038/s41598-021-92264-2.

Additional information:
¹ NCD Risk Factor Collaboration (NCD-RisC) (2016): Trends in adult body-mass index in 200 countries from 1975 to 2014: a pooled analysis of 1.698 population-based measurement studies with 19,2 million participants. Lancet 387: 1377–96.
http://www.thelancet.com/journals/lancet/article/PIIS0140- 6736%2816%2930054-X/fulltext
² http://www.aerzteblatt.de/archiv/160842
³ Wruck, W., Kawala, M.-A., Graffmann, N. & Adjaye, J. (2016): Strategies for identifying predictive biomarkers of non-alcoholic fatty liver disease. http://www.drugtargetreview.com/10985/content- type/articles/strategies-identifying-predictive-biomarkers-non-alcoholic-fatty-liver-disease/
⁴ Takahashi, Y., Soejima, Y. & Fukusato, T. (2012): Animal models of nonalcoholic fatty liver disease/nonalcoholic steatohepatitis. World J. Gastroenterol. 18 (19): 2300-2308.
⁵ https://www.gelbe-liste.de/arzneimitteltherapiesicherheit/cyp-interaktionen/cyp3a4