Exploration of novel pathway and genetic markers involved in dyslipidemia at post-GWAS era

2015 Fiscal Year Final Research Report

• Project/Area Number: 25461377
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Metabolomics
• Research Institution: Jichi Medical University
• Principal Investigator: Iwamoto Sadahiko 自治医科大学, 医学部, 教授 (10232711)
• Co-Investigator(Kenkyū-buntansha): NAKAYAMA KAZUHIRO 自治医科大学, 医学部, 講師 (90433581)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Keywords: 脂質代謝異常 / 非アルコール性脂肪肝 / SNP関連解析 / モデルマウス / 新規代謝パスウェイ / 分子間相互作用 / 遺伝環境相互作用

Outline of Final Research Achievements

Carbohydrate responsive element binding protein (ChREBP), a master regulator of hepatic lipogenesis, was identified as a novel binding partner of mammalian tribbles homologue 1 (TRIB1), the gene of which showed genetic association with plasma triglyceride levels. TRIB1 enhanced ChREBP proteolysis via ubiquitin-proteasome pathway. TRIB1 simultaneously enhanced mRNA expression of microsomal triglyceride transfer protein (MTTP), a principal molecule for VLDL secretion, via molecular interaction with Sin3A associated protein, 18kD. These two pathways may be involved in the genetic association of TRIB1 SNP in the enhancer element with plasma and hepatic lipid levels.
Furthermore, we discovered genetic association of Glucose-dependent insulinotropic polypeptide (GIP) with adiposity levels of visceral fat, which may be a predictive factor for the susceptibility to metabolic syndrome. We applied this result for a patent.

Free Research Field

医歯薬学