Molecular mechanism of adipose tissue healthy expansion and its medical application

2018 Fiscal Year Final Research Report

• Project/Area Number: 17K19686
• Research Category: Grant-in-Aid for Challenging Research (Exploratory)
• Allocation Type: Multi-year Fund
• Research Field: Internal medicine of the bio-information integration and related fields
• Research Institution: Kyushu University
• Principal Investigator: Ogawa Yoshihiro 九州大学, 医学研究院, 教授 (70291424)
• Research Collaborator: Tsuchiya Kyoichiro ; Itoh Michiko ; Miyachi Yasutaka ; Shiba Kumiko
• Project Period (FY): 2017-06-30 – 2019-03-31
• Keywords: 脂肪組織 / 異所性脂肪 / 肝臓 / NASH / SGLT2阻害薬

Outline of Final Research Achievements

SGLT2 inhibitors, an oral antidiabetic drug, promotes urinary excretion of glucose by blocking its reabsorption in the renal proximal tubules. Our data suggest that the phenotypic switch of adipose tissue macrophages (ATMs) could mediate healthy adipose tissue expansion; treatment with an SGLT2 inhibitor downregulates the gene expression of IL-15 in stromal cells (possibly ATMs) of the adipose tissue, thereby stimulating lipogenesis in adipocytes. Furthermore, SGLT2 inhibition has prevented or at least delayed the onset of NASH and eventually NASH-related hepatocellular carcinoma in association with adipose tissue healthy expansion.

Free Research Field

内科学、内分泌代謝学

Academic Significance and Societal Importance of the Research Achievements

SGLT2阻害薬投与により誘導される「脂肪組織のHealthy Expansion」の分子機構として細胞間相互作用による代謝ストレス軽減と異所性脂肪蓄積病態に対する臨床応用の可能性が明らかになった。減量による体脂肪量減少一辺倒の従来の肥満症治療とは全く発想が異なる新しい生活習慣病改善手法として、脂肪組織の健康的に増大による異所性脂肪蓄積減少を目指したNASHあるいはNASH肝癌の新しい治療戦略の開発につながる可能性が示唆された。