Metabolic syndrome caused by aberrant circadian rhythm and alternative splicing

2016 Fiscal Year Final Research Report

• Project/Area Number: 26461353
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Metabolomics
• Research Institution: Gunma University
• Principal Investigator: Satoh Tetsurou 群馬大学, 医学部附属病院, 講師 (40302484)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Keywords: 転写共役因子 / 遺伝子転写 / 選択的スプライシング / 脂肪細胞 / HELZ2 / THRAP3 / SFPQ

Outline of Final Research Achievements

We recently identified a novel transcriptional cofactor HELZ2 that binds to the nuclear receptor PPARγ and reported that HELZ2-deficient mice were resistant to high fat diet-induced obesity. We also identified THRAP3 and SFPQ as proteins binding to HELZ2 using immunoprecipitation/TOFMS analyses. In the present study, we found that THRAP3 knockdown in 3T3-L1 cells altered alternative splicing (AS) patterns of genes involved in lipid metabolism. Furthermore, knockdown of SFPQ suppressed adipocyte differentiation by altering AS of transcription factors in addition to the expression of transcription factors in the early differentiation. These findings together suggest that HELZ2-binding proteins could play important roles by regulating AS in the differentiation of white adipocytes.

Free Research Field

内分泌代謝学