Metabolic change in obese adipose tissue and adipocytokine dysregulation

2017 Fiscal Year Final Research Report

• Project/Area Number: 15K09412
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Metabolomics
• Research Institution: Osaka University
• Principal Investigator: Nishizawa Hitoshi 大阪大学, 医学系研究科, 講師 (20379259)
• Co-Investigator(Kenkyū-buntansha): 船橋 徹 大阪大学, 医学系研究科, 寄附講座教授 (60243234) ; 前田 法一 大阪大学, 医学系研究科, 寄附講座准教授 (30506308)
• Co-Investigator(Renkei-kenkyūsha): Nagamori Shushi 大阪大学, 大学院医学系研究科, 准教授 (90467572)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Keywords: ヒト脂肪組織 / プリン代謝 / ヒポキサンチン / 尿酸 / XOR / グルタミン酸 / アディポネクチン / TCAサイクル

Outline of Final Research Achievements

Little is known about the secretion of metabolites associated with purine catabolism in human white adipose tissue (hWAT). Human adipose tissue secreted hypoxanthine, a precursor of uric acid in purine catabolism, more than xanthine and uric acid. Hypoxanthine secretion and intracellular metabolites associated with purine biosynthesis were augmented under hypoxia in human adipocytes (Obesity, in press).
The static metabolic analyses showed that glutamate and constitutive metabolites of tricarboxylic acid (TCA) cycle were increased in WAT of obese mice. Moreover, in vivo metabolic turnover analyses demonstrated that glucose-derived these metabolites were dynamically and specifically produced in obese WAT. In adipocytes, glutamate treatment reduced adiponectin secretion and insulin-mediated glucose uptake and phosphorylation of Akt. These data suggest that high intra-adipocytes glutamate level potentially relates to adipocyte dysfunction in obesity (J.Biol.Chem. 2017).

Free Research Field

内分泌代謝内科学