Development of in vitro and in vivo assay systems to elucidate molecular mechanism suppressing obesity

2015 Fiscal Year Final Research Report

• Project/Area Number: 26670032
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Biological pharmacy
• Research Institution: University of Shizuoka
• Principal Investigator: SUGATANI JUNKO 静岡県立大学, 薬学部, 教授 (30098131)
• Co-Investigator(Kenkyū-buntansha): YAMAGUCHI MASAHIKO 静岡県立大学, 薬学部, 助教 (00632639)
• Project Period (FY): 2014-04-01 – 2016-03-31
• Keywords: PAF / PAF受容体 / PAF受容体欠損マウス / PAF受容体フロックスマウス / 肥満 / 褐色脂肪細胞 / UCP1 / UCP1クレマウス

Outline of Final Research Achievements

We investigated how PAF/PAF receptor signaling suppresses energy expenditure in vitro and in vivo. 　In cell lines differentiated to brown adipocytes, the effect of PAF to expression of UCP1 was rather low. In PAF receptor-knockout (PAFR-KO) mice, body and epididymal WAT weights were higher in PAFR-KO mice fed a high-fat diet (HFD) than in wild-type (WT) mice. TNF-alpha mRNA expression levels in epididymal WAT and the infiltration of CD11c-positive macrophages into epididymal WAT, which led to chronic inflammation, were also elevated in HFD-fed PAFR-KO mice. HFD-fed PAFR-KO mice had higher levels of fasting serum glucose than HFD-fed WT mice as well as impaired glucose tolerance. We also generated PAFR-floxed mice and crossed them with Adiponectin-Cre or Ucp1-Cre mice to generate white or brown adipocyte specific PAFR-KO mice, respectively. These knockout mice could be useful for studying PAF/PAF receptor dependent energy expenditure in vivo.

Free Research Field

医歯薬学