Background and Aims: Lipopolysaccharides (LPS) is increased in nonalcoholic fatty liver disease (NAFLD), but its relationship with liver inflammation is not defined. Approach and Results: We studied Escherichia coli LPS in patients with biopsy-proven NAFLD, 25 simple steatosis (nonalcoholic fatty liver) and 25 nonalcoholic 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 phosphorylated nuclear factor-κB expression. Toll-like receptor 4 positive (TLR4+) macrophages were higher in NASH than simple steatosis 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 with control mice and associated with nuclear factor-κB activation. Mice on aspirin developed lower fibrosis and extent compared with untreated ones. Treatment with TLR4 inhibitor resulted in lower liver inflammation in mice with NASH. Conclusions: In NAFLD, Escherichia coli LPS may increase liver damage by inducing macrophage and platelet activation through the TLR4 pathway.

Increased liver localization of lipopolysaccharides in human and experimental NAFLD / Carpino, G.; Del Ben, M.; Pastori, D.; Carnevale, R.; Baratta, F.; Overi, D.; Francis, H.; Cardinale, V.; Onori, P.; Safarikia, S.; Cammisotto, V.; Alvaro, D.; Svegliati-Baroni, G.; Angelico, F.; Gaudio, E.; Violi, F.. - In: HEPATOLOGY. - ISSN 0270-9139. - 72:2(2020), pp. 470-485. [10.1002/hep.31056]

Increased liver localization of lipopolysaccharides in human and experimental NAFLD

Carpino G.;Del Ben M.;Pastori D.;Carnevale R.;Baratta F.;Overi D.;Cardinale V.;Onori P.;Safarikia S.;Cammisotto V.;Alvaro D.;Angelico F.;Gaudio E.;Violi F.
2020

Abstract

Background and Aims: Lipopolysaccharides (LPS) is increased in nonalcoholic fatty liver disease (NAFLD), but its relationship with liver inflammation is not defined. Approach and Results: We studied Escherichia coli LPS in patients with biopsy-proven NAFLD, 25 simple steatosis (nonalcoholic fatty liver) and 25 nonalcoholic 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 phosphorylated nuclear factor-κB expression. Toll-like receptor 4 positive (TLR4+) macrophages were higher in NASH than simple steatosis 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 with control mice and associated with nuclear factor-κB activation. Mice on aspirin developed lower fibrosis and extent compared with untreated ones. Treatment with TLR4 inhibitor resulted in lower liver inflammation in mice with NASH. Conclusions: In NAFLD, Escherichia coli LPS may increase liver damage by inducing macrophage and platelet activation through the TLR4 pathway.
2020
NAFLD; lipopolysaccharides; liver
01 Pubblicazione su rivista::01a Articolo in rivista
Increased liver localization of lipopolysaccharides in human and experimental NAFLD / Carpino, G.; Del Ben, M.; Pastori, D.; Carnevale, R.; Baratta, F.; Overi, D.; Francis, H.; Cardinale, V.; Onori, P.; Safarikia, S.; Cammisotto, V.; Alvaro, D.; Svegliati-Baroni, G.; Angelico, F.; Gaudio, E.; Violi, F.. - In: HEPATOLOGY. - ISSN 0270-9139. - 72:2(2020), pp. 470-485. [10.1002/hep.31056]
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11573/1444831
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