Gut microbiota-mediated generation of saturated fatty acids elicits inflammation in the liver in murine high-fat diet-induced steatohepatitis

Shoji Yamada, Nobuhiko Kamada, Takeru Amiya, Nobuhiro Nakamoto, Toshiaki Nakaoka, Masaki Kimura, Yoshimasa Saito, Chieko Ejima, Takanori Kanai, Hidetsugu Saito

研究成果: Article

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Background: The gut microbiota plays crucial roles in the development of non-alcoholic steatohepatitis (NASH). However, the precise mechanisms by which alterations of the gut microbiota and its metabolism contributing to the pathogenesis of NASH are not yet fully elucidated. Methods: Mice were fed with a recently reported new class of high-fat diet (HFD), steatohepatitis-inducing HFD (STHD)-01 for 9weeks. The composition of the gut microbiota was analyzed by T-RFLP. Luminal metabolome was analyzed using capillary electrophoresis and liquid chromatography time-of-flight mass spectrometry (CE- and LC-TOFMS). Results: Mice fed the STHD-01 developed NASH-like pathology within a short period. Treatment with antibiotics prevented the development of NASH by STHD-01. The composition of the gut microbiota and its metabolic activities were markedly perturbed in the STHD-01-fed mice, and antibiotic administration normalized these changes. We identified that long-chain saturated fatty acid and n-6 fatty acid metabolic pathways were significantly altered by STHD-01. Of note, the changes in gut lipidome caused by STHD-01 were mediated by gut microbiota, as the depletion of the gut microbiota could reverse the perturbation of these metabolic pathways. A saturated long-chain fatty acid, palmitic acid, which accumulated in the STHD-01 group, activated liver macrophages and promoted TNF-α expression. Conclusions: Lipid metabolism by the gut microbiota, particularly the saturation of fatty acids, affects fat accumulation in the liver and subsequent liver inflammation in NASH.

元の言語English
記事番号136
ジャーナルBMC Gastroenterology
17
発行部数1
DOI
出版物ステータスPublished - 2017 11 29

ASJC Scopus subject areas

  • Gastroenterology

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