Regulation of lipid accumulation by new diabetes susceptible genes and the role of the epigenome

2014 Fiscal Year Final Research Report

• Project Area: Molecular Basis and Disorders of Control of Apetite and Fat Accumulation
• Project/Area Number: 23126101
• Research Category: Grant-in-Aid for Scientific Research on Innovative Areas (Research in a proposed research area)
• Allocation Type: Single-year Grants
• Review Section: Biological Sciences
• Research Institution: The University of Tokyo
• Principal Investigator: WAKI Hironori 東京大学, 医学部附属病院, 准教授 (00466765)
• Co-Investigator(Kenkyū-buntansha): IWABU Masato 東京大学, 医学部附属病院, 特任助教 (30557236) ; IWABU Miki 東京大学, 医学部附属病院, 特任助教 (70392529)
• Co-Investigator(Renkei-kenkyūsha): YAMAUCHI Toshimasa 東京大学, 医学部附属病院, 准教授 (40372370)
• Project Period (FY): 2011-04-01 – 2015-03-31
• Keywords: 糖尿病 / 肥満 / 疾患感受性遺伝子 / 転写

Outline of Final Research Achievements

In this study, we found that expression of CDKAL1 - one of susceptible genes for type 2 diabetes and obesity identified in genome-wide association studies - is regulated during adipocyte differentiation, hypertrophy and adiposity. Functionally, CDKAL1 works as a factor that suppresses adipocyte differentiation and lipid accumulation. Mechanistically, we found that CDKAL1 stimulates the Wnt/β-catenin pathway, which suppresses adipocyte differentiation. We also mapped a promoter region responsible for the suppression of adiponectin gene expression in adipocyte hypertrophy. A transcription factor named Heb1 binds and regulates transcription. Expression level of Heb1 itlsef is regulated by various metabolic stress signals in adipocytes.

Free Research Field

糖尿病・代謝内科