The role of coagulation factors in systemic metabolic homeostasis

2017 Fiscal Year Final Research Report

• Project/Area Number: 16K19531
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Metabolomics
• Research Institution: Niigata University
• Principal Investigator: Yoshida Yohko 新潟大学, 医歯学総合研究科, 特任助教 (00586232)
• Research Collaborator: MINAMINO Tohru ; SHIMIZU Ippei ; HAYASHI Yuka
• Project Period (FY): 2016-04-01 – 2018-03-31
• Keywords: 肥満 / 糖尿病 / 褐色脂肪 / 血液凝固因子

Outline of Final Research Achievements

It is known that metabolic stress causes brown adipose tissue (BAT) dysfunction and that coagulation factor Xa (FXa) is increased in obesity. Imposing a high fat diet (HFD) on C57BL/6NCr mice led to a marked increase in FXa and PAR1 in BAT. Administration of FXa inhibitor ameliorated the whitening of BAT, improved thermogenic response and glucose intolerance upon dietary obesity. In differentiated brown adipocytes, FXa markedly increased mitochondrial reactive oxygen species (ROS) and reduced mitochondrial membrane potential. The inhibition of PAR1 ameliorated FXa-induced mitochondrial ROS production and reduction in membrane potential. These results suggest the previously unknown role of coagulation systems in BAT in promoting the dysfunction of this organ leading to systemic metabolic disorders. The maintenance of BAT homeostasis through the suppression of FXa-PAR1 signaling would become a new therapeutic target for obesity and diabetes.

Free Research Field

循環器内科学