Recreating gut-liver axis during NAFLD onset by using a Caco-2/HepG2 co-culture system

Nonalcoholic fatty liver disease (NAFLD) onset and its progression towards nonalcoholic steatohepatitis (NASH) features increased intestinal permeability leaky gut, thereby favoring the escape of endotoxin [lipopolysaccharides (LPS)] from gut to liver. The aim this study was resemble crosstalk between intestine during NAFLD by using an in vitro model co-culture system. Enterocytes (Caco-2) were seeded on Transwell filters (pore size: 0.4 μm) cultured for 21 days constitute a confluent monolayer, then they co-cultivated with hepatocytes (HepG2) additional 24 h. Caco-2 apical chamber exposed LPS and/or mixture palmitic oleic acid (PAOA) FITC-4000 dextrans (FD4) across monolayer treatment cells PAOA LPS, consistently tight junction-associated proteins reduction. exposure PAOA/LPS promoted ApoB, triglyceride (TG), free secretion basolateral media. In turn, HepG2 co-cultured PAOA, or both accumulated lipid droplets intracellular TG content. Likewise, released pro-inflammatory cytokines These events triggered endoplasmic reticulum (ER) oxidative stress, enhancing reactive oxygen species (ROS), H2O2, aldehyde derivate production, ROS-induced DNA damage cells. Hence, Caco-2/HepG2 system may faithfully reproduce breach barrier integrity that occurs NAFLD, thus resulting inflammatory response ER which promote switch NASH.