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Increased Liver Localization of Lipopolysaccharides in Human and Experimental NAFLD
Author(s) -
Carpino Guido,
Del Ben Maria,
Pastori Daniele,
Carnevale Roberto,
Baratta Francesco,
Overi Diletta,
Francis Heather,
Cardinale Vincenzo,
Onori Paolo,
Safarikia Samira,
Cammisotto Vittoria,
Alvaro Domenico,
SvegliatiBaroni Gianluca,
Angelico Francesco,
Gaudio Eugenio,
Violi Francesco
Publication year - 2020
Publication title -
hepatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.488
H-Index - 361
eISSN - 1527-3350
pISSN - 0270-9139
DOI - 10.1002/hep.31056
Subject(s) - nonalcoholic fatty liver disease , tlr4 , medicine , inflammation , steatosis , fatty liver , fibrosis , lipopolysaccharide , endocrinology , liver biopsy , hepatocyte , biology , biopsy , biochemistry , disease , in vitro
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.