Roles of Macrophages on Brown Adipose Tissue Function in Obese Mice.

2023 Fiscal Year Final Research Report

• Project/Area Number: 21K08559
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 54040:Metabolism and endocrinology-related
• Research Institution: Kumamoto University
• Principal Investigator: Senokuchi Takafumi 熊本大学, 大学院生命科学研究部(医), 特任講師 (00530320)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: メタボリックシンドローム / マクロファージ / 褐色脂肪組織

Outline of Final Research Achievements

To verify the evidence of involvement of local macrophage proliferation on brown adipose tissue function in obese mice, we have generated transgenic mice whose macrophage proliferation is specifically suppressed by cyclin dependent kinase inhibitor, p27kip (Tg), and fed High-Fat Diet for 10 weeks. In the brown adipose tissue of Tg, less white adipocyte-lile lipid storage cell (Whitening of brown adipocytes) induced by obesity was observed, and anti-inflammatory M2 macrophage ratio was increased. Cald exposure at 4 degrees for 24 hours resulted in increase of macrophage numbers and inflammatory response in brown adipose tissue. The increase of UCP-1 mRNA expression in brown adipose tissue is suppressed by macrophage growth inhibition. These results suggested that regulation of the number of macrophages in brown adipose tissue could control its thermognenesis function, and possibly be one of the therapeutic targets for obesity-related metabolic disorders.

Free Research Field

代謝疾患

Academic Significance and Societal Importance of the Research Achievements

褐色脂肪組織におけるマクロファージの浸潤・増殖を制御することによる、全身のエネルギー代謝、インスリン抵抗性への影響を検討することで、褐色脂肪組織のエネルギー代謝を介した肥満、インスリン抵抗性の発症機序におけるマクロファージの果たす役割を明らかにする。さらに、インスリン抵抗性、肥満に対し、マクロファージ機能の制御が褐色脂肪組織の活性化調節を介した新たな治療法の開発につながる可能性を示した。