The effects of SREBP-1a on intestine homeostasis are determined using intestine- or macrophage- specific SREBP-1a KO mice

2020 Fiscal Year Final Research Report

• Project/Area Number: 19K22794
• Research Category: Grant-in-Aid for Challenging Research (Exploratory)
• Allocation Type: Multi-year Fund
• Review Section: Medium-sized Section 59:Sports sciences, physical education, health sciences, and related fields
• Research Institution: University of Toyama (2020); University of Tsukuba (2019)
• Principal Investigator: Nakagawa Yoshimi 富山大学, 学術研究部薬学・和漢系, 教授 (80361351)
• Project Period (FY): 2019-06-28 – 2021-03-31
• Keywords: SREBP-1a / 脂肪酸合成 / 小腸構造 / 小腸の発生・分化

Outline of Final Research Achievements

We generated SREBP-1a deficient (KO) and flox mice. In this mouse, the structure of the small intestine was abnormal, the villi were short, and the length of the entire small intestine was also shortened. Cell proliferation of cells in the small intestine was suppressed. In gene expression in the small intestine, the expression of fatty acid desaturation / elongation enzyme was suppressed, and oleic acid and palmitoleic acid were decreased. Fatty acid administration to SREBP-1a KO mice showed recovery of small intestinal structure. Growth was delayed due to SREBP-1a deficiency even in small intestinal organoid culture. Growth was restored by adding oleic acid and/or palmitoleic acid. We revealed that SREBP-1a has a crucial role in maintaining the structure of the small intestine.

Free Research Field

応用健康科学

Academic Significance and Societal Importance of the Research Achievements

SREBP-1aはSREBPファミリーの中でも生理的機能はあまりないと想定され、解析が進んでいなかった。それゆえ、遺伝子改変マウスの作製も遅れており、全身KOマウスおよび組織特異的KOマウスは存在していなかった。本研究で初めて全身KOおよびfloxマウスを作製したことの学術的意義は大きい。さらにSREBP-1a KOマウスでの小腸構造異常が見られることは脂質代謝が小腸構造の維持に必要であり、栄養代謝を調節する新たな知見を示した。新たな生活習慣病治療戦略の開発へ繋がる社会的な意義も大きい。