TY - JOUR
T1 - Gut microbiota confers host resistance to obesity by metabolizing dietary polyunsaturated fatty acids
AU - Miyamoto, Junki
AU - Igarashi, Miki
AU - Watanabe, Keita
AU - Karaki, Shin ichiro
AU - Mukouyama, Hiromi
AU - Kishino, Shigenobu
AU - Li, Xuan
AU - Ichimura, Atsuhiko
AU - Irie, Junichiro
AU - Sugimoto, Yukihiko
AU - Mizutani, Tetsuya
AU - Sugawara, Tatsuya
AU - Miki, Takashi
AU - Ogawa, Jun
AU - Drucker, Daniel J.
AU - Arita, Makoto
AU - Itoh, Hiroshi
AU - Kimura, Ikuo
N1 - Funding Information:
This work was supported by research grants from the JSPS and MEXT KAKENHI (grant nos. (JP15H05344 and JP16H01355, respectively) to I.K., AMED (no. JP18gm1010007) to I.K., CIHR Foundation (grant 154321) to D.J.D., the Institute for Fermentation Osaka to IK, and the Smoking Research Foundation to IK. We thank NITTO PHARMACEUTICAL INDUSTRIES, LTD. for supplying purified HYA, Kanako Igarashi, Miwa Yoshimoto, and Mie Honda for their help with metabolome analysis, Kumiko Tachi-kawa, Mai Arita, and Shizuka Kasuga for their help with fatty acid analysis and in vitro assays, Yukie Katayama for 16S rRNA gene sequence analysis, Kohey Kitao and Keiko Hisa for their valuable discussions, and Dr. Tadahiro Kitamura for the GLUTag cells.
Publisher Copyright:
© 2019, The Author(s).
PY - 2019/12/1
Y1 - 2019/12/1
N2 - 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.
AB - 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.
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U2 - 10.1038/s41467-019-11978-0
DO - 10.1038/s41467-019-11978-0
M3 - Article
C2 - 31488836
AN - SCOPUS:85071762031
SN - 2041-1723
VL - 10
JO - Nature Communications
JF - Nature Communications
IS - 1
M1 - 4007
ER -
