NDLI: Tissue factor-PAR2 signaling promotes diet-induced obesity and adipose inflammation

Content Provider	PubMed Central
Author	Badeanlou, Leylla Christian, Furlan-freguia Yang, Guang Ruf, Wolfram Samad, Fahumiya
Abstract	Tissue factor (TF), the initiator of the coagulation cascade, mediates coagulation factor VIIa-dependent activation of protease activated receptor-2 (PAR2). Here we delineate an unexpected role for coagulation signaling in obesity and its complications. Mice lacking PAR2 (F2rl1) or the cytoplasmic domain of TF (F3) are protected from high fat diet (HFD) induced weight gain and insulin resistance. In hematopoietic cells, genetic deletion of TF-PAR2 signaling reduces adipose tissue macrophage inflammation and specific pharmacological inhibition of macrophage TF signaling rapidly ameliorates insulin resistance. In contrast, non-hematopoietic cell TF-VIIa-PAR2 signaling specifically promotes obesity. Mechanistically, adipocyte TF cytoplasmic domain dependent VIIa signaling suppresses Akt phosphorylation with concordant adverse transcriptional changes of key regulators of obesity and metabolism. Pharmacological blockade of adipocyte TF in vivo reverses these effects of TF-VIIa signaling and rapidly improves energy expenditure. Thus, TF signaling is a potential therapeutic target to improve impaired metabolism and insulin resistance in obesity.
Related Links	http://dx.doi.org/10.1038/nm.2461
Ending Page	1497
Page Count	8
Starting Page	1490
File Format	PDF
ISSN	10788956
e-ISSN	1546170X
Journal	Nature medicine
Issue Number	11
Volume Number	17
Language	English
Publisher Date	2011-10-01
Access Restriction	Open
Subject Keyword	Biochemistry, Genetics and Molecular Biology(all) Medicine(all) Research in Higher Education
Content Type	Text
Resource Type	Article
Subject	Medicine Biochemistry, Genetics and Molecular Biology

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