Increased Liver Localization of Lipopolysaccharides in Human and Experimental NAFLD - PubMed (original) (raw)

. 2020 Aug;72(2):470-485.

doi: 10.1002/hep.31056. Epub 2020 May 22.

Maria Del Ben 2, Daniele Pastori 2, Roberto Carnevale 3 4, Francesco Baratta 2, Diletta Overi 5, Heather Francis 6, Vincenzo Cardinale 3, Paolo Onori 5, Samira Safarikia 7, Vittoria Cammisotto 8, Domenico Alvaro 7, Gianluca Svegliati-Baroni 9, Francesco Angelico 10, Eugenio Gaudio 5, Francesco Violi 2 4

Affiliations

Increased Liver Localization of Lipopolysaccharides in Human and Experimental NAFLD

Guido Carpino et al. Hepatology. 2020 Aug.

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 by the American Association for the Study of Liver Diseases.

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References

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