In vitro hepatic steatosis model based on gut-liver-on-a-chip

Abstract

Hepatic steatosis, also known as fatty liver disease, occurs due to abnormal lipid accumulation in the liver. It has been known that gut absorption also plays an important role in the mechanism underlying hepatic steatosis. Conventional in vitro cell culture models have limitations in recapitulating the mechanisms of hepatic steatosis because it does not include the gut absorption process. Previously, we reported development of a microfluidic gut-liver chip that can recapitulate the gut absorption of fatty acids and subsequent lipid accumulation in liver cells. In this study, we performed a series of experiments to verify that our gut-liver chip reproduces various aspects of hepatic steatosis. The absorption of fatty acids was evaluated under various culture conditions. The anti-steatotic effect of turofexorate isopropyl (XL-335) and metformin was tested, and both drugs showed different action mechanisms. In addition, the oxidative stress induced by lipid absorption was evaluated. Our results demonstrate the potential of the gut-liver chip for use as a novel, physiologically realistic in vitro model to study fatty liver disease.