The molecular mechanism of organ metabolic disease state and abnormal brain function caused by Elovl6-mediated qualitative changes of fatty acids

2017 Fiscal Year Final Research Report

• Project/Area Number: 15H02541
• Research Category: Grant-in-Aid for Scientific Research (A)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Metabolomics
• Research Institution: University of Tsukuba
• Principal Investigator: Shimano Hitoshi 筑波大学, 医学医療系, 教授 (20251241)
• Co-Investigator(Kenkyū-buntansha): 松坂 賢 筑波大学, 医学医療系, 准教授 (70400679) ; 中川 嘉 筑波大学, 国際統合睡眠医科学研究機構, 准教授 (80361351)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Keywords: 脂肪酸伸長酵素 / 脂肪毒性 / インスリン抵抗性 / 糖尿病 / 脳

Outline of Final Research Achievements

Liver-specific Elovl6 KO mice showed enhanced hepatic insulin signaling when they were fed high-sucrose diet or were crossed with ob/ob mice. Through transcriptome and lipidomics analysis, we identified and characterized gene X and lipid Y as hepatic insulin signaling regulators. To define the role of Elovl6 in type 2 diabetes development, we assessed the effects of Elovl6 deletion in leptin receptor-deficient C57BL/KsJ db/db mice. The db/db-Elovl6 KO mice had a markedly increased β-cell mass with increased proliferation and decreased apoptosis, an adaptive increase in insulin, and improved glycemic control. Elovl6 is a fundamental factor linking dysregulated lipid metabolism to β-cell dysfunction, islet inflammation, and β-cell apoptosis in diabetes. Moreover, we found the crucial role of Elovl6 in neural stem cell function and found the key lipid that regulate neural stem cell function.

Free Research Field

代謝・内分泌学