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Decreased liver B vitamin-related enzymes as a metabolic hallmark of cancer cachexia

Author

Listed:
  • Yasushi Kojima

    (Aichi Cancer Center Research Institute)

  • Emi Mishiro-Sato

    (Aichi Cancer Center Research Institute)

  • Teruaki Fujishita

    (Aichi Cancer Center Research Institute)

  • Kiyotoshi Satoh

    (Keio University)

  • Rie Kajino-Sakamoto

    (Aichi Cancer Center Research Institute)

  • Isao Oze

    (Aichi Cancer Center Research Institute)

  • Kazuki Nozawa

    (Aichi Cancer Center Hospital)

  • Yukiya Narita

    (Aichi Cancer Center Hospital)

  • Takatsugu Ogata

    (Aichi Cancer Center Hospital)

  • Keitaro Matsuo

    (Aichi Cancer Center Research Institute)

  • Kei Muro

    (Aichi Cancer Center Hospital)

  • Makoto Mark Taketo

    (Kyoto University, Yoshida-Konoe-cho)

  • Tomoyoshi Soga

    (Keio University)

  • Masahiro Aoki

    (Aichi Cancer Center Research Institute
    Nagoya University Graduate School of Medicine)

Abstract

Cancer cachexia is a complex metabolic disorder accounting for ~20% of cancer-related deaths, yet its metabolic landscape remains unexplored. Here, we report a decrease in B vitamin-related liver enzymes as a hallmark of systemic metabolic changes occurring in cancer cachexia. Metabolomics of multiple mouse models highlights cachexia-associated reductions of niacin, vitamin B6, and a glycine-related subset of one-carbon (C1) metabolites in the liver. Integration of proteomics and metabolomics reveals that liver enzymes related to niacin, vitamin B6, and glycine-related C1 enzymes dependent on B vitamins decrease linearly with their associated metabolites, likely reflecting stoichiometric cofactor-enzyme interactions. The decrease of B vitamin-related enzymes is also found to depend on protein abundance and cofactor subtype. These metabolic/proteomic changes and decreased protein malonylation, another cachexia feature identified by protein post-translational modification analysis, are reflected in blood samples from mouse models and gastric cancer patients with cachexia, underscoring the clinical relevance of our findings.

Suggested Citation

  • Yasushi Kojima & Emi Mishiro-Sato & Teruaki Fujishita & Kiyotoshi Satoh & Rie Kajino-Sakamoto & Isao Oze & Kazuki Nozawa & Yukiya Narita & Takatsugu Ogata & Keitaro Matsuo & Kei Muro & Makoto Mark Tak, 2023. "Decreased liver B vitamin-related enzymes as a metabolic hallmark of cancer cachexia," Nature Communications, Nature, vol. 14(1), pages 1-23, December.
    • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-41952-w
    DOI: 10.1038/s41467-023-41952-w
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    References listed on IDEAS

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    1. Rin Mizuno & Hiroaki Hojo & Masatomo Takahashi & Soshiro Kashio & Sora Enya & Motonao Nakao & Riyo Konishi & Mayuko Yoda & Ayano Harata & Junzo Hamanishi & Hiroshi Kawamoto & Masaki Mandai & Yutaka Su, 2022. "Remote solid cancers rewire hepatic nitrogen metabolism via host nicotinamide-N-methyltransferase," Nature Communications, Nature, vol. 13(1), pages 1-13, December.
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