Increased liver localization of lipopolysaccharides in human and experimental non-alcoholic fatty liver disease

Lipopolysaccharides (LPS) is increased in non-alcoholic fatty liver disease (NAFLD), but its relationship with liver inflammation is not defined. We studied Escherichia Coli-LPS in patients with biopsy-proven NAFLD, 25 simple steatosis (NAFL), and 25 non-alcoholic steatohepatitis (NASH), and in mice with diet-induced NASH. NASH patients had higher serum LPS and hepatocytes LPS localization than controls, which was correlated with serum zonulin and pNF-κB expression. Toll-like receptor 4 positive (TLR4+ ) macrophages were higher in NASH than NAFL or controls and correlated with serum LPS. NASH biopsies showed a higher CD61+ platelets, and most of them were TLR4+ . TLR4+ platelets correlated with serum LPS values. In mice with NASH, LPS serum levels and LPS hepatocyte localization were increased compared to control mice and associated with NF-κB activation. Mice on aspirin developed lower fibrosis and extent compared to untreated ones. Treatment with TLR4 inhibitor resulted in lower liver inflammation in mice with NASH. Conclusion: In NAFLD, Escherichia Coli-LPS may increase liver damage by inducing macrophage and platelet activation through the TLR4 pathway