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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.
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,Ikuo Kimura