Remote solid cancers rewire hepatic nitrogen metabolism via host nicotinamide-N-methyltransferase

DOI 機関リポジトリ (HANDLE) HANDLE PDF Web Site ほか1件をすべて表示 一部だけ表示 被引用文献3件 参考文献44件 オープンアクセス
  • 水野, 林
    Inter-Organ Communication Research Team, Institute for Life and Medical Sciences, Kyoto University; Department of Gynecology and Obstetrics, Kyoto University Graduate School of Medicine
  • 北條, 広朗
    Inter-Organ Communication Research Team, Institute for Life and Medical Sciences, Kyoto University; The Thomas N. Sato BioMEC-X Laboratories, Advanced Telecommunications Research Institute International (ATR); ERATO Sato Live Bio-forecasting Project, Japan Science and Technology Agency (JST)
  • 髙橋, 政友
    Division of Metabolomics, Research Center for Transomics Medicine, Medical Institute of Bioregulation, Kyushu University
  • 樫尾, 宗志朗
    Department of Genetics, Graduate School of Pharmaceutical Sciences, The University of Tokyo
  • 塩谷, 天
    The Thomas N. Sato BioMEC-X Laboratories, Advanced Telecommunications Research Institute International (ATR); ERATO Sato Live Bio-forecasting Project, Japan Science and Technology Agency (JST)
  • 中尾, 素直
    Division of Metabolomics, Research Center for Transomics Medicine, Medical Institute of Bioregulation, Kyushu University
  • 小西, 理予
    Inter-Organ Communication Research Team, Institute for Life and Medical Sciences, Kyoto University
  • 依田, 真由子
    Inter-Organ Communication Research Team, Institute for Life and Medical Sciences, Kyoto University
  • 原田, 綾乃
    Inter-Organ Communication Research Team, Institute for Life and Medical Sciences, Kyoto University
  • 濵西, 潤三
    Department of Gynecology and Obstetrics, Kyoto University Graduate School of Medicine
  • 河本, 宏
    Laboratory of Immunology, Institute for Frontier Life and Medical Sciences, Kyoto University
  • 万代, 昌紀
    Department of Gynecology and Obstetrics, Kyoto University Graduate School of Medicine
  • 鈴木, 穣
    Graduate School of Frontier Science, The University of Tokyo
  • 三浦, 正幸
    Department of Genetics, Graduate School of Pharmaceutical Sciences, The University of Tokyo
  • 馬場, 健史
    Division of Metabolomics, Research Center for Transomics Medicine, Medical Institute of Bioregulation, Kyushu University
  • 和泉, 自泰
    Division of Metabolomics, Research Center for Transomics Medicine, Medical Institute of Bioregulation, Kyushu University
  • 河岡, 慎平
    Inter-Organ Communication Research Team, Institute for Life and Medical Sciences, Kyoto University; The Thomas N. Sato BioMEC-X Laboratories, Advanced Telecommunications Research Institute International (ATR); ERATO Sato Live Bio-forecasting Project, Japan Science and Technology Agency (JST); Department of Integrative Bioanalytics, Institute of Development, Aging and Cancer (IDAC), Tohoku University

説明

Cancers disrupt host homeostasis in various manners but the identity of host factors underlying such disruption remains largely unknown. Here we show that nicotinamide-N-methyltransferase (NNMT) is a host factor that mediates metabolic dysfunction in the livers of cancer-bearing mice. Multiple solid cancers distantly increase expression of Nnmt and its product 1-methylnicotinamide (MNAM) in the liver. Multi-omics analyses reveal suppression of the urea cycle accompanied by accumulation of amino acids, and enhancement of uracil biogenesis in the livers of cancer-bearing mice. Importantly, genetic deletion of Nnmt leads to alleviation of these metabolic abnormalities, and buffers cancer-dependent weight loss and reduction of the voluntary wheel-running activity. Our data also demonstrate that MNAM is capable of affecting urea cycle metabolites in the liver. These results suggest that cancers up-regulate the hepatic NNMT pathway to rewire liver metabolism towards uracil biogenesis rather than nitrogen disposal via the urea cycle, thereby disrupting host homeostasis.

収録刊行物

被引用文献 (3)*注記

もっと見る

参考文献 (44)*注記

もっと見る

関連プロジェクト

もっと見る

キーワード

詳細情報 詳細情報について

問題の指摘

ページトップへ