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

Research output: Contribution to journal › Journal article › Research › peer-review

Standard

Coagulation factors promote brown adipose tissue dysfunction and abnormal systemic metabolism in obesity. / Hayashi, Yuka; Shimizu, Ippei; Yoshida, Yohko; Ikegami, Ryutaro; Suda, Masayoshi; Katsuumi, Goro; Fujiki, Shinya; Ozaki, Kazuyuki; Abe, Manabu; Sakimura, Kenji; Okuda, Shujiro; Hayano, Toshiya; Nakamura, Kazuhiro; Walsh, Kenneth; Jespersen, Naja Zenius; Nielsen, Søren; Scheele, Camilla; Minamino, Tohru.

In: iScience, Vol. 25, No. 7, 104547, 2022.

Research output: Contribution to journal › Journal article › Research › peer-review

Harvard

Hayashi, Y, Shimizu, I, Yoshida, Y, Ikegami, R, Suda, M, Katsuumi, G, Fujiki, S, Ozaki, K, Abe, M, Sakimura, K, Okuda, S, Hayano, T, Nakamura, K, Walsh, K, Jespersen, NZ, Nielsen, S, Scheele, C & Minamino, T 2022, 'Coagulation factors promote brown adipose tissue dysfunction and abnormal systemic metabolism in obesity', iScience, vol. 25, no. 7, 104547. https://doi.org/10.1016/j.isci.2022.104547

APA

Hayashi, Y., Shimizu, I., Yoshida, Y., Ikegami, R., Suda, M., Katsuumi, G., Fujiki, S., Ozaki, K., Abe, M., Sakimura, K., Okuda, S., Hayano, T., Nakamura, K., Walsh, K., Jespersen, N. Z., Nielsen, S., Scheele, C., & Minamino, T. (2022). Coagulation factors promote brown adipose tissue dysfunction and abnormal systemic metabolism in obesity. iScience, 25(7), [104547]. https://doi.org/10.1016/j.isci.2022.104547

Vancouver

Hayashi Y, Shimizu I, Yoshida Y, Ikegami R, Suda M, Katsuumi G et al. Coagulation factors promote brown adipose tissue dysfunction and abnormal systemic metabolism in obesity. iScience. 2022;25(7). 104547. https://doi.org/10.1016/j.isci.2022.104547

Author

Hayashi, Yuka ; Shimizu, Ippei ; Yoshida, Yohko ; Ikegami, Ryutaro ; Suda, Masayoshi ; Katsuumi, Goro ; Fujiki, Shinya ; Ozaki, Kazuyuki ; Abe, Manabu ; Sakimura, Kenji ; Okuda, Shujiro ; Hayano, Toshiya ; Nakamura, Kazuhiro ; Walsh, Kenneth ; Jespersen, Naja Zenius ; Nielsen, Søren ; Scheele, Camilla ; Minamino, Tohru. / Coagulation factors promote brown adipose tissue dysfunction and abnormal systemic metabolism in obesity. In: iScience. 2022 ; Vol. 25, No. 7.

Bibtex

@article{d04c4101375445d099d9856acd785f84,
title = "Coagulation factors promote brown adipose tissue dysfunction and abnormal systemic metabolism in obesity",
abstract = "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.",
keywords = "Biological sciences, Cell biology, Human metabolism, Human Physiology",
author = "Yuka Hayashi and Ippei Shimizu and Yohko Yoshida and Ryutaro Ikegami and Masayoshi Suda and Goro Katsuumi and Shinya Fujiki and Kazuyuki Ozaki and Manabu Abe and Kenji Sakimura and Shujiro Okuda and Toshiya Hayano and Kazuhiro Nakamura and Kenneth Walsh and Jespersen, {Naja Zenius} and S{\o}ren Nielsen and Camilla Scheele and Tohru Minamino",
note = "Publisher Copyright: {\textcopyright} 2022 The Author(s)",
year = "2022",
doi = "10.1016/j.isci.2022.104547",
language = "English",
volume = "25",
journal = "iScience",
issn = "2589-0042",
publisher = "Elsevier",
number = "7",

}

RIS

TY - JOUR

T1 - Coagulation factors promote brown adipose tissue dysfunction and abnormal systemic metabolism in obesity

AU - Hayashi, Yuka

AU - Shimizu, Ippei

AU - Yoshida, Yohko

AU - Ikegami, Ryutaro

AU - Suda, Masayoshi

AU - Katsuumi, Goro

AU - Fujiki, Shinya

AU - Ozaki, Kazuyuki

AU - Abe, Manabu

AU - Sakimura, Kenji

AU - Okuda, Shujiro

AU - Hayano, Toshiya

AU - Nakamura, Kazuhiro

AU - Walsh, Kenneth

AU - Jespersen, Naja Zenius

AU - Nielsen, Søren

AU - Scheele, Camilla

AU - Minamino, Tohru

N1 - Publisher Copyright: © 2022 The Author(s)

PY - 2022

Y1 - 2022

N2 - 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.

AB - 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.

KW - Biological sciences

KW - Cell biology

KW - Human metabolism

KW - Human Physiology

U2 - 10.1016/j.isci.2022.104547

DO - 10.1016/j.isci.2022.104547

M3 - Journal article

C2 - 35754738

AN - SCOPUS:85132225480

VL - 25

JO - iScience

JF - iScience

SN - 2589-0042

IS - 7

M1 - 104547

ER -

ID: 313649187