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2016 Fiscal Year Final Research Report

Elucidation of tetrahydrobiopterin-induced BAT differentiation and regulation of glucose as well as energy metabolism

Research Project

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Project/Area Number 15K19514
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeMulti-year Fund
Research Field Metabolomics
Research InstitutionKyoto University

Principal Investigator

Fujita Yoshihito  京都大学, 医学研究科, 助教 (50547809)

Project Period (FY) 2015-04-01 – 2017-03-31
Keywords褐色脂肪 / 糖尿病 / 肥満 / eNOS
Outline of Final Research Achievements

Brown adipose tissue (BAT) is a central organ that acts to increase energy expenditure; its regulatory factors could be clinically useful in the treatment of obesity. Tetrahydrobiopterin (BH4) is an essential co-factor of tyrosine hydroxylase and nitric oxide synthase (NOS). Although BH4 regulates the known regulatory factors of BAT such as noradrenaline (NA) and nitric oxide (NO), participation of BH4 in BAT function remains unclear. We investigate the role of BH4 in the regulation of BAT. Hph-1 mice, a mouse model of BH4 deficiency, exhibit obesity, adiposity, glucose intolerance, insulin resistance, and impaired BAT function. By BAT transplantation from BH4-sufficient mice (control mice) into BH4-deficient mice, impaired BAT function was ameliorated together with systemic metabolic disturbances, strongly suggesting that BH4-induced BAT has a critical role in the regulation of systemic energy metabolism. Taken together, BH4 activates BAT and regulates systemic energy metabolism.

Free Research Field

糖尿病

URL: 

Published: 2018-03-22  

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