Elucidation of the Molecular Mechanisms of Interorgan Communication Factors Involved in Brown Adipose Tissue Regeneration

2023 Fiscal Year Final Research Report

• Project/Area Number: 21K08532
• 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: Sakaguchi Masaji 熊本大学, 大学院生命科学研究部(医), 助教 (90625774)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: 糖尿病 / 褐色脂肪組織 / 肥満 / インスリン抵抗性 / ベージュ化 / ミトコンドリア

Outline of Final Research Achievements

The applicants have identified Serine protease inhibitor A1 (SerpinA1), secreted from the liver, as a candidate for a new brown fat activation factor. Lliver-specific SerpinA1 overexpressing transgenic (Tg) mice, improved glucose tolerance and increased expression of UCP1 in brown adipose tissue, and increased heat production under cold stimulation. Furthermore, SerpinA1 knockout (KO) mice created using CRISPR/Cas9 showed glucose intolerance, increased insulin resistance, decreased oxygen consumption, and cold intolerance. These analyses suggest that SerpinA1 is a hepatokine that activates the mitochondrial function in brown adipose tissue.

Free Research Field

糖尿病・代謝内分泌学

Academic Significance and Societal Importance of the Research Achievements

SerpinA1は、糖代謝の改善に寄与する新しい臓器連関因子として、糖尿病治療の新規分子標的として期待できる。SerpinA1の作用機序と、ヒトにおけるSerpinA1の役割が明らかになることで、今後の臨床応用への展望が開ける可能性がある。本研究における動物モデルで得られた知見を基に、今後、SerpinA1の詳細な作用機序について明らかにしていきたい。