Mechanisms of adipose tissue-specific expression and action of D-dopachrome tautomrase

2017 Fiscal Year Final Research Report

• Project/Area Number: 15K11040
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Functional basic dentistry
• Research Institution: The University of Tokushima
• Principal Investigator: IWATA Takeo 徳島大学, 大学院医歯薬学研究部(歯学系), 助教 (10350399)
• Co-Investigator(Kenkyū-buntansha): 水澤 典子 徳島大学, 大学院医歯薬学研究部(歯学系), 助教 (80254746) ; 吉本 勝彦 徳島大学, 大学院医歯薬学研究部(歯学系), 教授 (90201863)
• Co-Investigator(Renkei-kenkyūsha): MINAKAWA Noriaki 徳島大学, 大学院医歯薬学研究部, 教授 (40209820)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Keywords: アディポカイン / 転写調節 / 肥満 / 脂肪細胞 / AMPK

Outline of Final Research Achievements

Transcriptional regulation of D-dopachrome tautomerase (DDT), an adipokine with anti-obesity property, is largely unknown. We first screened molecules affecting DDT transcription from a chemical library. Several derivatives of AICAR, an AMP-activated protein kinase (AMPK) activator, were found to induce DDT transcription. Furthermore, an AMPK inhibitor decreased DDT mRNA levels in adipocytes differentiated from SGBS cells, a human preadipocyte cell line, suggesting involvement of AMPK in DDT transcription. Next, we investigated involvement of FOXO1 and mTOR pathways downstream of AMPK activation in the transcription of DDT gene. FOXO1 enhanced and inhibited DDT transcription in HEK293 cells and SGBS cells, respectively. Cell-type specific effects were also observed in the DDT gene expression of cells treated with AS1842856, a FOXO1 inhibitor. Furthermore, rapamycin, an mTOR inhibitor, enhanced DDT mRNA levels in SGBS adipocytes.

Free Research Field

薬理学