Investigation of down regulation mechanism of Lect2 gene expression by metformin

• Project/Area Number: 15K19509
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Metabolomics
• Research Institution: Kanazawa University
• Principal Investigator: Takayama Hiroaki 金沢大学, 医学系, 技術職員 (90725227)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000); Fiscal Year 2017: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2016: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2015: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
• Keywords: Lect2 / Metformin / AMPK / PKA / LECT2 / メトホルミン / ヘパトカイン / miRNA

Outline of Final Research Achievements

A hepatokine leukocyte cell-derived chemotaxin 2（LECT2）which is overproduced with obesity cause insulin resistance in skeletal muscle. It is expected that suppression of LECT2 production is a new therapeutic target of insulin resistance, but no drug is known which lowering LECT2 production to date. Here I revealed that an oral anti-diabetic drug metformin can suppress Lect2 gene expression via AMPK activation in cultured hepatocyte. This pathway may relate RNA instability mechanism because metformin did not alter LECT2 promoter activity. Further experiment is needed to understand the molecular mechanism in this pathway much more.