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査読

35 被引用数 (Scopus)

抄録

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.

本文言語English
論文番号136
ジャーナルBMC Gastroenterology
17
1
DOI
出版ステータスPublished - 2017 11月 29

ASJC Scopus subject areas

  • 消化器病学

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