Study of microRNAs to act on a lipid homeostasis transcription factor MLXIPL

2021 Fiscal Year Final Research Report

• Project/Area Number: 19K07198
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 47060:Clinical pharmacy-related
• Research Institution: Health Sciences University of Hokkaido
• Principal Investigator: SHIBAYAMA Yoshihiko 北海道医療大学, 薬学部, 教授 (90593822)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: マイクロRNA

Outline of Final Research Achievements

MLXIPL is a transcription factor which activates genes expression associated triglycerides metabolism in a concentration-dependent manner by carbohydrate concentration. It was not clear that specific microRNAs (miR) binding to MLXIPL mRNA. Complementarily miRs counteracting MLXIPL mRNA were investigated in the present study. MiR-127 and miR-129 were significantly degraded MLXIPL mRNA. Expression levels of miR-127 and miR-134 in the liver was significantly increased in high-fat diet (HFD) fed mice, as well as expression levels in the serum significantly increased. HFD feeding altered histone acetylation. Histone acetylation levels of upstream promoter region of miR-127 gene was significantly increased in HFD fed mice compared with standard diet fed mice. It was reported that MLXIPL have important role in histone acetylation. These results suggested that miR-127 may affect MLXIPL expression level, result in alteration histone acetylation.

Free Research Field

臨床薬剤学

Academic Significance and Societal Importance of the Research Achievements

食事環境は生活習慣病の発症に影響する重要な因子であるが、その分子生物学的機序は不明な点が多い。本研究ではトリグリセリド合成や糖質濃度依存的にエピジェネティックな変化を司る転写因子であるMLXIPLと、その相補的なマイクロRNA（miR）に着目して研究を行った。miR-127はMLXIPLを抑制すること、高脂肪食により肝臓と血清での発現量が上昇することを見出した。高脂肪食は生活習慣病の発症に影響するが、本研究の結果はmiR-127とMLXIPLが薬物治療およびバイオマーカーとして応用できる可能性を示唆している。