Coagulation factors promote brown adipose tissue dysfunction and abnormal systemic metabolism in obesity.
Biological sciences
Cell biology
Human Physiology
Human metabolism
Journal
iScience
ISSN: 2589-0042
Titre abrégé: iScience
Pays: United States
ID NLM: 101724038
Informations de publication
Date de publication:
15 Jul 2022
15 Jul 2022
Historique:
received:
03
02
2022
revised:
11
04
2022
accepted:
02
06
2022
entrez:
27
6
2022
pubmed:
28
6
2022
medline:
28
6
2022
Statut:
epublish
Résumé
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.
Identifiants
pubmed: 35754738
doi: 10.1016/j.isci.2022.104547
pii: S2589-0042(22)00819-7
pmc: PMC9218513
doi:
Types de publication
Journal Article
Langues
eng
Pagination
104547Informations de copyright
© 2022 The Author(s).
Déclaration de conflit d'intérêts
The authors except for T.M. disclose no conflicts of interest. T.M. discloses the joint research funds and the remuneration for a lecture from Bayer; however, this company did not play a role in the study design, data collection and analysis, decision to publish, or preparation of the article.
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