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Nat Commun. 2019 Sep 5;10(1):4007. doi: 10.1038/s41467-019-11978-0.

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

Author information

1
Department of Applied Biological Science, Graduate School of Agriculture, Tokyo University of Agriculture and Technology, Fuchu-shi, Tokyo, 183-8509, Japan.
2
AMED-CREST, Japan Agency for Medical Research and Development, Chiyoda-ku, Tokyo, 100-0004, Japan.
3
Laboratory of Physiology, Department of Environmental and Life Sciences, University of Shizuoka, Shizuoka, 422-8526, Japan.
4
Division of Applied Life Sciences, Graduate School of Agriculture, Kyoto University, Kitashirakawa Oiwake-cho, Sakyo-ku, Kyoto, 606-8502, Japan.
5
Department of Biological Chemistry, Graduate School of Pharmaceutical Sciences, Kyoto University, Kyoto, 606-8501, Japan.
6
K-CONNEX, Keihanshin Consortium for Fostering the Next Generation of Global Leaders in Research, Kyoto, 606-8501, Japan.
7
Department of Endocrinology, Metabolism and Nephrology, School of Medicine, Keio University, Shinjuku-ku, Tokyo, 160-8582, Japan.
8
Department of Pharmaceutical Biochemistry, Graduate School of Pharmaceutical Sciences, Kumamoto University, Kumamoto, 862-0973, Japan.
9
Research and Education Center for Prevention of Global Infectious Diseases of Animals, Faculty of Agriculture, Tokyo University of Agriculture and Technology, Fuchu-shi, Tokyo, 183-0045, Japan.
10
Division of Applied Biosciences, Graduate School of Agriculture, Kyoto University, Kyoto, 606-8502, Japan.
11
Department of Medical Physiology, Graduate School of Medicine, Chiba University, Chiba, 260-8670, Japan.
12
Department of Medicine, Lunenfeld Tanenbaum Research Institute, Mount Sinai Hospital, University of Toronto, Toronto, ON M5S 2J7, Canada.
13
Division of Physiological Chemistry and Metabolism, Faculty of Pharmacy, Keio University, 1-5-30, Shibakoen, Minato-ku, Tokyo, 105-0011, Japan.
14
Laboratory for Metabolomics, RIKEN Center for Integrative Medical Sciences, Kanagawa, 230-0045, Japan.
15
Department of Applied Biological Science, Graduate School of Agriculture, Tokyo University of Agriculture and Technology, Fuchu-shi, Tokyo, 183-8509, Japan. ikimura@cc.tuat.ac.jp.
16
AMED-CREST, Japan Agency for Medical Research and Development, Chiyoda-ku, Tokyo, 100-0004, Japan. ikimura@cc.tuat.ac.jp.

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.

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