Elucidation of the mechanism by which depletion of M2 macrophages promotes beige/browning of white adipose tissue

2021 Fiscal Year Final Research Report

• Project/Area Number: 19K18002
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 54040:Metabolism and endocrinology-related
• Research Institution: University of Toyama
• Principal Investigator: Igarashi Yoshiko 富山大学, 学術研究部医学系, 特命助教 (30837688)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: ベージュ脂肪細胞

Outline of Final Research Achievements

White adipose tissue (WAT), commonly referred to as 'fat', are energy-storing adipose tissue, whereas beige adipocytes, induced upon cold stimulation, dissipates stored energy as heat. How depletion of M2-like Mφ regulate beige or browning of WAT remains unknown. I examined the role of CD206 M2-like macrophages in the browning of WAT by using genetically engineered CD206DTR mice, in which CD206 M2-like Mφ were conditionally depleted. I report that depletion of CD206 M2-like Mφ promotes beiging or browning of WAT, and induces proliferation of beige progenitors upon cold stimulation, Depletion of CD206 M2-like Mφ results in improved glucose tolerance and enhanced systemic insulin sensitivity upon cold stimulation. We attributed this phenomenon to the downregulation of TGF-β signaling. Furthermore, in order to clarify the mechanism of this enhanced beige/browning phenomenon by depletion of CD206 M2-like Mφ, we generated another genetically engineered mice.

Free Research Field

肥満

Academic Significance and Societal Importance of the Research Achievements

M2マクロファージの除去は脂肪組織中のベージュ脂肪細胞を効率よく増加させた。この発見は、エネルギーを蓄積しやすい体質からエネルギーを燃焼しやすい体質へと変化させるために、M2マクロファージの働きを制御することが重要であることを示した。これは、代謝疾患を持つ人々にとどまらず、代謝の高い健康的な体作りにM2マクロファージが重要な役割を持つことを示し、本研究成果を応用することで、運動に頼らない、新しい体質改善方法を見出せる可能性を持つ。