Glutamine metabolism network linked to obesity, diabetes mellitus and tumorigenesis

2016 Fiscal Year Final Research Report

• Project/Area Number: 26430105
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Tumor biology
• Research Institution: Chiba University
• Principal Investigator: SUZUKI Sawako 千葉大学, 医学部附属病院, 助教 (60400892)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Keywords: グルタミン代謝 / エネルギー代謝 / 抗酸化作用 / 生活習慣病 / 肝癌

Outline of Final Research Achievements

Recently, several meta analyses revealed obesity and diabetes are oncogenic risk factors and associated with a rise of incidence, prevalence, and the mortality of the cancer. In this context, I focused on the glutamine metabolism which is the main energy source for cancer development. And we reported that GLS2, which is the central in the conversion of glutamine to glutamate, is localized in the mitochondria and promotes the TCA cycle via α-ketoglutarate. On the other hand, at the same time, GLS2 increases production of glutathione to antagonize the reactive oxygen species levels. In this study, I examined the roles of GLS2 in life-style related diseases and cancer development in vivo using Gls2 knockout mice. We found that high fat diet Gls2 knockout mice showed decreased survival and presented so-called metabolic syndrome such as obesity, diabetes and dyslipidemia. Furthermore, we revealed that Gls2 knockout mice developed early-onset hepatocellular carcinoma.

Free Research Field

内分泌代謝、癌とエネルギー代謝