Elucidating the Mechanisms by which Periodontitis Exacerbates NAFLD in Mice with High-Carbohydrate Diet-Induced Fatty Liver Disease

2023 Fiscal Year Final Research Report

• Project/Area Number: 21K09894
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 57030:Conservative dentistry-related
• Research Institution: Hiroshima University
• Principal Investigator: Kurihara Hidemi 広島大学, 医系科学研究科(歯), 名誉教授 (40161765)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: 高炭水化物食 / NAFLD / 歯周炎

Outline of Final Research Achievements

This study aimed to establish a non-alcoholic fatty liver disease (NAFLD) mouse model without the confounding factors of obesity and diabetes by using a high carbohydrate diet (HCD), and to elucidate the direct impact of periodontitis on NAFLD. As a result, it was demonstrated that HCD induces fatty liver without causing obesity or diabetes. Furthermore, when experimental ligature-induced periodontitis was introduced to the HCD-induced NAFLD mouse model, there was a significant increase in liver fat accumulation, indicating that periodontitis exacerbates NAFLD.
These findings suggest that periodontitis can directly affect liver metabolism and worsen NAFLD without the intermediary effects of obesity and diabetes. This study highlights the potential of using an HCD-induced NAFLD model to better understand the direct interactions between periodontitis and liver disease, providing a valuable tool for further research in this area.

Free Research Field

歯周病

Academic Significance and Societal Importance of the Research Achievements

これまでの高脂肪食誘導性NAFLDマウスモデルは、糖尿病・肥満を併発するものであった。実臨床での患者ケースを良く模倣している一方で、実験ツールとしては複数の因子が絡み合うため、歯周炎による肝臓代謝への直接的影響の解明には適さなかった。
本研究で樹立した、高炭水化物誘導性NAFLDマウスモデルは、糖尿病・肥満が成立する前に脂肪肝を呈するため、歯周炎の直接的な影響検証に有効な新規実験ツールとなる。実際に、本モデルを用いて、肝臓に移行した歯周病原性細菌が肝臓代謝障害の原因となることを見出しており、将来の新規NAFLD予防・治療法開発のための基盤となる知見を提供できたことの意義は大きい。