Coagulation factors promote brown adipose tissue dysfunction and abnormal systemic metabolism in obesity

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  • Yuka Hayashi
  • Ippei Shimizu
  • Yohko Yoshida
  • Ryutaro Ikegami
  • Masayoshi Suda
  • Goro Katsuumi
  • Shinya Fujiki
  • Kazuyuki Ozaki
  • Manabu Abe
  • Kenji Sakimura
  • Shujiro Okuda
  • Toshiya Hayano
  • Kazuhiro Nakamura
  • Kenneth Walsh
  • Naja Zenius Jespersen
  • Søren Nielsen
  • Schéele, Camilla Charlotte Nielsen
  • Tohru Minamino

Brown adipose tissue (BAT) has a role in maintaining systemic metabolic health in rodents and humans. Here, we show that metabolic stress induces BAT to produce coagulation factors, which then—together with molecules derived from the circulation—promote BAT dysfunction and systemic glucose intolerance. When mice were fed a high-fat diet (HFD), the levels of tissue factor, coagulation Factor VII (FVII), activated coagulation Factor X (FXa), and protease-activated receptor 1 (PAR1) expression increased significantly in BAT. Genetic or pharmacological suppression of coagulation factor-PAR1 signaling in BAT ameliorated its whitening and improved thermogenic response and systemic glucose intolerance in mice with dietary obesity. Conversely, the activation of coagulation factor-PAR1 signaling in BAT caused mitochondrial dysfunction in brown adipocytes and systemic glucose intolerance in mice fed normal chow. These results indicate that BAT produces endogenous coagulation factors that mediate pleiotropic effects via PAR1 signaling under metabolic stress.

Original languageEnglish
Article number104547
Issue number7
Number of pages23
Publication statusPublished - 2022

Bibliographical note

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© 2022 The Author(s)

    Research areas

  • Biological sciences, Cell biology, Human metabolism, Human Physiology

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