Search for the novel molecules involved in brown adipocyte activation

2020 Fiscal Year Final Research Report

• Project/Area Number: 18K16208
• 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: Kumamoto University
• Principal Investigator: Sakaguchi Masaji 熊本大学, 大学院生命科学研究部(医), 助教 (90625774)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Keywords: 糖尿病 / インスリン抵抗性 / 褐色脂肪組織 / インスリンシグナル / ミトコンドリア / 再生 / 肥満

Outline of Final Research Achievements

In order to identify the molecules involved in the activation of brown adipose tissues, we employed the proteomics analysis using the serum from the inducible adipocyte-specific IR and IGF1R knockout mice. We selected the candidate molecules that altered significantly and confirmed their differences in comparison with those of controls by the qPCR. We tentatively designated this molecule brown adipocyte activator (BAF) that derived from the liver. The addition of BAF induced the proliferation of brown adipocyte progenitor cells in vitro, promoted mitochondrial activity. BAF was also shown to act on white adipocytes, inducing beige adipocyte. These results confirmed that BAF is a novel soluble factor involved in activating both white and brown adipocytes. To furthermore investigate the impact of BAF in vivo, we created liver-specific BAF transgenic mice (BAF-Tg).

Free Research Field

糖尿病・代謝内分泌学

Academic Significance and Societal Importance of the Research Achievements

BAFはメタボリックシンドロームにおける肝臓‐脂肪の臓器連関に深く関わっていると考えられ、糖尿病治療の新規分子標的として期待できる。BAFの作用機序の解明をすすめると同時に、in vivoでの機能解析をすすめていくことで、今後の臨床応用への展望を開く可能性がある。本成果報告として、褐色脂肪前駆細胞の増殖及び再生を誘導する新規生理活性因子を網羅的に検索し、候補分子BAFを確定することができた。今後、褐色脂肪細胞前駆細胞の分化、増殖を誘導する因子（BAF）の作用機序を明らかにしていきたい。