Year: 2013
Type: dissertation
Abstract: Background: There is considerable evidence that intestinal microbiota are involved in the development of metabolic syndromes and consequently with that of nonalcoholic fatty liver disease (NAFLD).Toll-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 nonalcoholic steatohepatitis (NASH) or NAFLD remains unclear.In this study, we investigated the role of fatty acids in triggering the development of a pro-inflammatory state of NAFLD.Methods: NAFLD was induced in mice fed a high fat diet.The mice were sacrificed and the expressions of TLRs, tumor necrosis factor (TNF), interleukin 1β (IL-1β), 2 CXCL2, and phospho-interleukin-1 receptor-associated kinase 1 in the liver and small intestine were assessed.In addition, Huh7 and THP-1 cells, both of which are representatives of hepatocytes and Kupffer cells, respectively, were treated with palmitic acid, and the direct effects of fatty acids on TLR induction by these cells were evaluated.Results: The expressions of inflammatory cytokines such as TNF, IL-1β, and TLRs-2, -4, -5, and -9 were increased in the liver, but decreased in the small intestine of high fat diet-fed mice in vivo.In addition, the expressions of TLRs in Huh7 and THP-1 cells were increased by treatment with fatty acids. Conclusion:In the development of the pro-inflammatory state of NAFLD, fatty acids trigger the expressions of TLRs, which contribute to the induction of inflammatory cytokines through TLR signals by the intestinal microbiota.
Authors: 澤田, 康司, サワダ, コウジ, Sawada, Kouji
Institution: Asahikawa Medical University
Language: English
Subfield: Hepatology
Field: Medicine
Domain: Health Sciences
Open Access status: green
OpenAlex ID: W6988694307