Obesity-induced gut microbial metabolite promotes liver cancer through senescence secretome

Shin Yoshimoto, Tze Mun Loo, Koji Atarashi, Hiroaki Kanda, Seidai Sato, Seiichi Oyadomari, Yoichiro Iwakura, Kenshiro Oshima, Hidetoshi Morita, Masahira Hattori, Kenya Honda, Yuichi Ishikawa, Eiji Hara () and Naoko Ohtani
Additional contact information
Shin Yoshimoto: Cancer Institute, Japanese Foundation for Cancer Research, Koto-ku, Tokyo 135-8550, Japan
Tze Mun Loo: Cancer Institute, Japanese Foundation for Cancer Research, Koto-ku, Tokyo 135-8550, Japan
Koji Atarashi: Research Center for Allergy and Immunology, RIKEN, Yokohama, Kanagawa 230-0045, Japan
Hiroaki Kanda: Cancer Institute, Japanese Foundation for Cancer Research, Koto-ku, Tokyo 135-8550, Japan
Seidai Sato: Cancer Institute, Japanese Foundation for Cancer Research, Koto-ku, Tokyo 135-8550, Japan
Seiichi Oyadomari: Institute for Genome Research, University of Tokushima, Tokushima 770-8503, Japan
Yoichiro Iwakura: Research Institute for Biological Science, Tokyo University of Science, Noda, Chiba 278-8510, Japan
Kenshiro Oshima: Graduate School of Frontier Sciences, University of Tokyo, Kashiwa, Chiba 277-8561, Japan
Hidetoshi Morita: School of Veterinary Medicine, Azabu University, Sagamihara, Kanagawa 229-8501, Japan
Masahira Hattori: Graduate School of Frontier Sciences, University of Tokyo, Kashiwa, Chiba 277-8561, Japan
Kenya Honda: CREST, Japan Science and Technology Agency, Kawaguchi, Saitama 332-0012, Japan
Yuichi Ishikawa: Cancer Institute, Japanese Foundation for Cancer Research, Koto-ku, Tokyo 135-8550, Japan
Eiji Hara: Cancer Institute, Japanese Foundation for Cancer Research, Koto-ku, Tokyo 135-8550, Japan
Naoko Ohtani: Cancer Institute, Japanese Foundation for Cancer Research, Koto-ku, Tokyo 135-8550, Japan

Nature, 2013, vol. 499, issue 7456, 97-101

Abstract: Obesity is shown in a mouse model of liver cancer to strongly enhance tumorigenesis; a high fat diet alters the composition of intestinal bacteria, leading to more production of the metabolite DCA which, probably together with other factors, induces senescence and the secretion of various senescence-associated cytokines in hepatic stellate cells, thus promoting cancer.

Date: 2013
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DOI: 10.1038/nature12347

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