The mechanism of systemic nutrient metabolism through the maintenance of small intestinal structure and intestinal environment by the interaction of small intestinal constituent cells

2023 Fiscal Year Final Research Report

• Project/Area Number: 22K19705
• 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
• Principal Investigator: Yoshimi Nakagawa 富山大学, 学術研究部薬学・和漢系, 教授 (80361351)
• Project Period (FY): 2022-06-30 – 2024-03-31
• Keywords: CREBH / 生活習慣病

Outline of Final Research Achievements

CREBH is a transcription factor that regulates lipid and glucose metabolism in the liver and small intestine. I have previously demonstrated that lipid metabolism in the liver is disrupted in CREBH-deficient mice, leading to the exacerbation of lifestyle-related diseases such as fatty liver disease. This study reveals that CREBH-deficient mice also exhibit abnormalities in the internal structure of the small intestine, leading to the weakening of intestinal barrier function and alterations in the gut microbiota. An increase in gut bacteria contributing to the worsening of Metabolic dysfunction-associated steatotic liver disease (MASLD) was observed, highlighting the importance of small intestinal CREBH function in the prevention and improvement of lifestyle-related diseases.

Free Research Field

応用健康科学

Academic Significance and Societal Importance of the Research Achievements

Metabolic dysfunction-associated steatohepatitis (MASH:旧NASH)の患者数は年々増加しているが、有効な治療薬は存在しない。MASHは終末像として肝がんにまで増悪化するがその機序は不明瞭である。その中で、本研究からMASH病態の発症・がん化に対して肝臓、小腸の両者におけるCREBHの機能が保護的に作用していることが明らかになり、CREBHがMASH治療におけるキーファクターとなりうる可能性を示した。