Evaluation of a mechanism of lifestyle-related diseases focusing on the initiate-regulation of adipocyte differentiation by the clock system

2019 Fiscal Year Final Research Report

• Project/Area Number: 16K18954
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Medical pharmacy
• Research Institution: Tokyo University of Science, Yamaguchi (2019); Jichi Medical University (2016-2018)
• Principal Investigator: Ushijima Kentaro 山陽小野田市立山口東京理科大学, 薬学部, 教授 (70448843)
• Project Period (FY): 2016-04-01 – 2020-03-31
• Keywords: 時計遺伝子 / インスリン感受性 / 脂肪細胞分化 / 前駆脂肪細胞

Outline of Final Research Achievements

The animal experiments using ob/ob mice showed that the distribution of adipocytes was shifted to a smaller cell size and insulin sensitivity was improved by entinostat. These changes were considered to be due to the increased expression of
Ppar-γ (regulator of adipocyte differentiation) mediated by the increase of DBP protein.
In a study using human visceral adipose tissue, mRNA expressions of Dbp and Ppar-γ were also significantly lower in type 2 diabetic patients than in non-diabetic patients. These observations were similar to those in animal experiments. Such a difference between type 2 diabetic patients and non-diabetic patients was observed in omental adipose tissue, but not in mesenteric adipose tissue.

Free Research Field

時間生物学

Academic Significance and Societal Importance of the Research Achievements

本研究により、脂肪細胞の分化調節における時計遺伝子Dbpの役割が明らかとなった。また、糖尿病における内臓脂肪内Dbp発現量の低下はマウスのみならず、ヒト内臓脂肪組織（大網脂肪）においても同様に観察された。これらの成果は、体内時計による恒常性維持機構の理解に新たな知見を与えるものである。
今後、Dbp発現量を上昇させる手法を開発することで、新たな糖尿病の治療方法を開拓できると期待できる。また、糖尿病患者の内臓脂肪組織においてDbp発現が低下している主原因を明らかにすることで、新たな病態解明や疾患発症リスクを提唱できる。