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Augmented hepatic T oll‐like receptors by fatty acids trigger the pro‐inflammatory state of non‐alcoholic fatty liver disease in mice
Author(s) -
Sawada Koji,
Ohtake Takaaki,
Hasebe Takumu,
Abe Masami,
Tanaka Hiroki,
Ikuta Katsuya,
Suzuki Yasuaki,
Fujiya Mikihiro,
Hasebe Chitomi,
Kohgo Yutaka
Publication year - 2014
Publication title -
hepatology research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.123
H-Index - 75
eISSN - 1872-034X
pISSN - 1386-6346
DOI - 10.1111/hepr.12199
Subject(s) - fatty liver , steatohepatitis , gut flora , tumor necrosis factor alpha , receptor , inflammation , proinflammatory cytokine , medicine , liver injury , immunology , endocrinology , biology , disease
Aim There is considerable evidence that intestinal microbiota are involved in the development of metabolic syndromes and, consequently, with the development of non‐alcoholic fatty liver disease ( NAFLD ). T oll‐like receptors ( TLRs ) are essential for the recognition of microbiota. However, the induction mechanism of TLR signals through the gut‐liver axis for triggering the development of non‐alcoholic steatohepatitis ( NASH ) or NAFLD remains unclear. In this study, we investigated the role of palmitic acid ( PA ) in triggering the development of a pro‐inflammatory state of NAFLD . Methods Non‐alcoholic fatty liver disease was induced in mice fed a high fat diet ( HFD ). The mice were killed and the expression of TLRs , tumor necrosis factor ( TNF ), interleukin ( IL )‐1β, and phospho‐interleukin‐1 receptor‐associated kinase 1 in the liver and small intestine were assessed. In addition, primary hepatocytes and K upffer cells were treated with PA , and the direct effects of PA on TLRs induction by these cells were evaluated. Results The expression of inflammatory cytokines such as TNF , IL ‐1β, and TLR ‐2, ‐4, ‐5, and ‐9 was increased in the liver, but decreased in the small intestine of HFD ‐fed mice in vivo . In addition, the expression of TLRs in primary hepatocytes and K upffer cells was increased by treatment with PA . Conclusion In the development of the pro‐inflammatory state of NAFLD , PA triggers the expression of TLRs , which contribute to the induction of inflammatory cytokines through TLR signals by intestinal microbiota.