Roles of Hypothalamic Akt on Food Intake and Glucose Metabolism

2017 Fiscal Year Final Research Report

• Project/Area Number: 15K09398
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Metabolomics
• Research Institution: Chiba University (2017); Saitama Medical University (2015-2016)
• Principal Investigator: Ono Hiraku 千葉大学, 大学院医学研究院, 講師 (10570616)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Keywords: Akt / 視床下部 / 摂食 / インスリン感受性

Outline of Final Research Achievements

Insulin is known to function in the arcuate nucleus of the hypothalamus to suppress food intake as well as suppress hepatic glucose production indirectly, via PI 3-kinase pathway. The most important molecule downstream of PI 3-kinase is Akt, while its role in the hypothalamus is unclear. In this study we bidirectionally modified Akt activity specifically in the arcuate nucleus of rats and investigated effects on food intake and glucose metabolism.
Overexpression of constitutively-active Akt or dominant-negative Akt in the arcuate nucleus unexpectedly did not significantly change food intake or body weight. On the other hand, hypothalamic constitutive activation of Akt ameliorated high fat diet-induced hepatic insulin resistance, suggesting a divergence of pathway toward regulation of food intake and that toward glucose metabolism exist downstream of PI 3-kinase, only latter of which is what Akt is responsible.

Free Research Field

代謝学