| Budget Amount *help |
¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2017: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2016: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
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| 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.
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