Hepatic steatosis is a process of abnormal lipid deposition within the liver cells, often caused by excessive alcohol uptake or obesity. A conventional in vitro model for hepatic steatosis uses a liver cell culture, treated with fatty acids and measures accumulation of lipids within the cells. This model does not recapitulate the complex process of absorption and metabolism of digestive lipids. Here, we introduce a gut-liver chip, which mimics the gut absorption and hepatic metabolism in a microfluidic chip. Absorption of fatty acids through gut layer and subsequent deposition within liver cells was demonstrated. Tumor necrosis factor-α, butyrate, and α-lipoic acid were chosen as model molecules that can affect hepatic steatosis via different mechanisms, and their effects were evaluated. Our results suggest that the gut-liver chip can mimic the absorption and accumulation of fatty acids in the gut and the liver.

The liver plays important roles in drug metabolism and homeostasis. The metabolism and biotransformation can not only affect the efficacy of drugs but also result in hepatotoxicity and drug-induced liver injury. Understanding the complex physiology of the liver and the pathogenetic mechanisms of liver diseases is essential for drug development. Conventional in vitro models have limitations in the ability to predict drug effects, due to the lack of physiological relevance. Recently, the liver-on-a-chip platform has been developed to reproduce the microarchitecture and in vivo environment of the liver. These efforts have improved the physiological relevance of the liver tissue used in the platform and have demonstrated its applicability to drug screening and disease models. In this review, we summarize the recent development of liver-on-a-chip models that closely mimic the in vivo liver environments and liver diseases.

No abstract

No abstract