The role of endoplasmic reticulum sensor ATF6beta in diabetes and obesity

2022 Fiscal Year Final Research Report

• Project/Area Number: 20K08909
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 54040:Metabolism and endocrinology-related
• Research Institution: The University of Tokushima
• Principal Investigator: MIYAKE Masato 徳島大学, 先端酵素学研究所, 准教授 (30588976)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: 肥満 / 糖尿病 / 小胞体 / ATF6 / 肝臓

Outline of Final Research Achievements

This study aims to elucidate the role of endoplasmic reticulum stress sensor ATF6β in obesity and diabetes and establish the molecular basis as a therapeutic target. A previous study revealed that conventional knock out of ATF6βprevent obesity and diabetes when mice fed with a high-fat diet. We found that liver-specific knock-out of ATF6β has no obvious phenotype related to obesity and diabetes compared to control in mice. To understand the role of the ATF6 pathway, tissue-specific ATF6β, and its paralog ATF6α double knockout mice were established. Among skeletal muscle, adipose tissue, monocyte, and liver, we found that liver-specific ATF6β/ATF6α double knockout mice prevent obesity and diabetes when mice fed a high-fat diet. More studies will reveal the importance of ATF6β on obesity and diabetes and lead to the establishment of a therapeutic target.

Free Research Field

代謝学

Academic Significance and Societal Importance of the Research Achievements

小胞体ストレスは肥満や糖尿病で生じるストレスであり、創薬標的となりうることが示されている。一方で、ATF6経路の意義は十分に解明されておらず、その解明は新たな治療標的の開発につながる可能性がある。本研究によって、肝臓におけるATF6が肥満や糖尿病において重要であることが示され、今後のさらなる研究により新規の治療標的となりうるだけでなく、生物学的意義がまだ十分にわかっていないATF6経路の分子機構に迫ることができる。