Gut microbiota confers host resistance to obesity by metabolizing dietary polyunsaturated fatty acids

Junki Miyamoto, Miki Igarashi, Keita Watanabe, Shin-ichiro Karaki, Hiromi Mukouyama, Shigenobu Kishino, Xuan Li, Atsuhiko Ichimura, Junichiro Irie, Yukihiko Sugimoto, Tetsuya Mizutani, Tatsuya Sugawara, Takashi Miki, Jun Ogawa, Daniel J. Drucker, Makoto Arita, Hiroshi Itoh and Ikuo Kimura ()
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Junki Miyamoto: Tokyo University of Agriculture and Technology
Miki Igarashi: Tokyo University of Agriculture and Technology
Keita Watanabe: Tokyo University of Agriculture and Technology
Shin-ichiro Karaki: University of Shizuoka
Hiromi Mukouyama: Tokyo University of Agriculture and Technology
Shigenobu Kishino: Kyoto University, Kitashirakawa Oiwake-cho
Xuan Li: Tokyo University of Agriculture and Technology
Atsuhiko Ichimura: Kyoto University
Junichiro Irie: AMED-CREST, Japan Agency for Medical Research and Development
Yukihiko Sugimoto: AMED-CREST, Japan Agency for Medical Research and Development
Tetsuya Mizutani: Tokyo University of Agriculture and Technology
Tatsuya Sugawara: Kyoto University
Takashi Miki: Chiba University
Jun Ogawa: Kyoto University, Kitashirakawa Oiwake-cho
Daniel J. Drucker: University of Toronto
Makoto Arita: Keio University
Hiroshi Itoh: AMED-CREST, Japan Agency for Medical Research and Development
Ikuo Kimura: Tokyo University of Agriculture and Technology

Nature Communications, 2019, vol. 10, issue 1, 1-15

Abstract: Abstract Gut microbiota mediates the effects of diet, thereby modifying host metabolism and the incidence of metabolic disorders. Increased consumption of omega-6 polyunsaturated fatty acid (PUFA) that is abundant in Western diet contributes to obesity and related diseases. Although gut-microbiota-related metabolic pathways of dietary PUFAs were recently elucidated, the effects on host physiological function remain unclear. Here, we demonstrate that gut microbiota confers host resistance to high-fat diet (HFD)-induced obesity by modulating dietary PUFAs metabolism. Supplementation of 10-hydroxy-cis-12-octadecenoic acid (HYA), an initial linoleic acid-related gut-microbial metabolite, attenuates HFD-induced obesity in mice without eliciting arachidonic acid-mediated adipose inflammation and by improving metabolic condition via free fatty acid receptors. Moreover, Lactobacillus-colonized mice show similar effects with elevated HYA levels. Our findings illustrate the interplay between gut microbiota and host energy metabolism via the metabolites of dietary omega-6-FAs thereby shedding light on the prevention and treatment of metabolic disorders by targeting gut microbial metabolites.

Date: 2019
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DOI: 10.1038/s41467-019-11978-0

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