Gut–liver on a chip toward an in vitro model of hepatic steatosis

Abstract

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.

Liver‐on‐a‐Chip Models of Fatty Liver Disease

“…Steatosis was quantified after treatment with α-lipolic acid (ALA), butyrate, and tumor necrosis factor (TNF)-α. ALA decreased TAG accumulation in both chips and 2D cultures. (24,28) Butyrate decreased steatosis by enhancing intestinal barrier function and decreasing TAG accumulation in hepatocytes. (29,30) TNF-α induced steatosis by affecting intestines, increasing steatosis in chip-based studies, but not in 2D monolayers.…”

“…(D) A reversibly and irreversibly injured ALD model where the development of fibrosis can be seen. Reprinted (A) with permission from Public Library of Science, (B) from Baishideng Publishing Group, (C) from John Wiley & Sons, and (D) from Royal Society of Chemistry …”

“…For example, for one device consisting of two chambers separated by a porous membrane with a collagen scaffold on the intestinal side, Caco‐2 cells were seeded in the intestinal chamber and HepG2 cells in the hepatic chamber (Fig. C) . Cells were perfused with media containing OA and PA for 24 hours after perfusing serum‐free media for 24 hours.…”

“…3C). (24) Cells were perfused with media containing OA and PA for 24 hours after perfusing serum-free media for 24 hours. Steatosis was quantified after treatment with α-lipolic acid (ALA), butyrate, and tumor necrosis factor (TNF)-α. ALA decreased TAG accumulation in both chips and 2D cultures.…”

Application of Impedance-Based Techniques in Hepatology Research

“…Lee and Sung [69] have produced a model mimicking the absorption of fatty acids to assess the interaction between the two tissues, allowing assessment of the multifactorial systems involved in hepatic steatosis, or fatty liver disease. There are many components to hepatic steatosis and the mechanisms of disease are still not fully understood.…”