Effect of a high-fat diet-induced epithelial barrier dysfunction at a young age on disease development.

2023 Fiscal Year Final Research Report

• Project/Area Number: 20K17007
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 53010:Gastroenterology-related
• Research Institution: National Center for Global Health and Medicine
• Principal Investigator: Nakata Kazuaki 国立研究開発法人国立国際医療研究センター, 研究所, 臨床連携研究室 研究員 (20849244)
• Project Period (FY): 2020-04-01 – 2024-03-31
• Keywords: 食事脂質 / 脂肪酸 / 腸上皮細胞 / 腫瘍形成 / 大腸癌

Outline of Final Research Achievements

We aimed to clarify the effects of different dietary fatty acids (FAs) on intestinal epithelial cell turnover and tumorigenesis. In this study, we compared the influences of high-fat diets (HFD) in which lard, a main source of FAs, was replaced with saturated or unsaturated FAs. We found that mice fed the saturated FA-containing HFD exhibited a higher number of Ki67+ proliferating cells than those fed the unsaturated FA-containing HFD. In the murine models, intestinal tumorigenesis was accelerated in mice fed the saturated FA-containing HFD compared to those fed the unsaturated FA-containing HFD. Furthermore, the inhibition of saturated FA-binding proteins canceled the impact of saturated FA on intestinal epithelial cell proliferation and tumorigenesis. These results collectively indicate that dietary saturated FA disrupts intestinal epithelial homeostasis and eventually promotes tumorigenesis via the saturated FA-binding protein.

Free Research Field

腸上皮細胞

Academic Significance and Societal Importance of the Research Achievements

本研究成果は、飽和脂肪酸の過剰摂取を避けることにより腸管腫瘍形成を予防できるという可能性を示す、社会的意義の高いものである。また、飽和脂肪酸が腸上皮細胞回転ならびに腫瘍形成を促進するために必要な分子としてその結合たんぱく質を同定しており、本分子を介するシグナル伝達経路を阻害する分子の開発は、新規の腸管腫瘍予防・治療法に繋がる可能性がある。