Unraveling of the regulation of lifestyle-related diseases through the immune system in the lipid synthetic transcription factor SREBP

2020 Fiscal Year Final Research Report

• Project/Area Number: 19K20124
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 59040:Nutrition science and health science-related
• Research Institution: Tokyo University of Agriculture
• Principal Investigator: KEMURIYAMA Noriko 東京農業大学, 応用生物科学部, 助教 (50747350)
• Project Period (FY): 2019-04-01 – 2021-03-31
• Keywords: SREBP / 小胞体ストレス / 生活習慣病 / NASH

Outline of Final Research Achievements

In this study, we investigated the role of SREBPs during endoplasmic reticulum (ER) stress, and investigated the involvement of SREBPs in lifestyle-related diseases by investigating their interfering effects other than lipid metabolism. Gene expression analyses by SREBP knockdown treatment or overexpressing cells were performed by RNA-seq. and qPCR. As a result of this study, we identified immune gene X, which was altered during endoplasmic reticulum stress, as a novel target gene for SREBPs. It was found to be upregulated in the livers of NASH model mice through the development of fibrosis around the expressed cells, and partially involved in the activation of hepatic stellate cells. The present results indicated that SREBPs may participate in the chronic inflammation occurring in NASH through the regulation of the immune system.

Free Research Field

代謝・栄養学

Academic Significance and Societal Importance of the Research Achievements

これまで生活習慣病態解明に対する研究は、根源的原因とされる肥満・脂肪肝の改善、あるいは炎症制御に対してそれぞれ別の因子に焦点が当てられた研究が主であった。本研究はエネルギー代謝転写因子が、代謝面だけでなく、炎症系への干渉作用をも持ち合わせて病態の発症・進展を制御する可能性を明らかにするという新しい視点で検討し、効率的な生活習慣病の予防・治療の開発を目指す点において、学術的・社会学的意義は大きいと思われる。