Clarification of the regulation of acipocyte function and the mechanism maintaining metabolic homeostasis by ketone body in adipocytes

2023 Fiscal Year Final Research Report

• Project/Area Number: 21K16369
• 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: Osaka University
• Principal Investigator: Nishitani Shigeki 大阪大学, 大学院医学系研究科, 助教 (30889407)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: ケトン体 / 脂肪細胞

Outline of Final Research Achievements

Adipocyte is essential in regulating metabolic homeostasis during feeding/fasting cycle. We revealed that adipocyte produces ketone body (3HBA).
Hmgcs2 is the first rate-limiting enzyme of ketogenesis. From database analysis and in vivo and in vitro experiments, we found that adipose tissue and adipocytes express Hmgcs2, and that adipocytes produce and secrete 3HBA. Treatment with 3HBA enhanced the gene expression levels of the antioxidative stress factors, PPARγ, and lipogenic factors in adipose tissue in vivo and in adipocytes in vitro, accompanied by reduced ROS levels. Knockdown of endogenous Hmgcs2 in adipocytes markedly decreased 3HBA levels in adipocytes and decreased the gene expression levels of the antioxidative stress factors, PPARγ, and lipogenic factors with increased ROS levels. Our results demonstrate that 3HBA plays significant roles in enhancing the function of adipocytes.

Free Research Field

内分泌学、代謝学

Academic Significance and Societal Importance of the Research Achievements

脂肪細胞は飢餓状態において脂肪分解を介して脂肪酸を供給する臓器であるが、今回の研究によって脂肪細胞はケトン体を産生することが明らかになった。さらに、ケトン体は栄養状態に応じて産生され、局所的に作用することで脂肪細胞機能を制御することが明らかになった。脂肪組織はエネルギー貯蔵臓器であることから、栄養状態を鋭敏に感知することで、脂肪細胞局所で脂肪酸分解や糖取り込み、中性脂肪蓄積が制御されることは合理的なホメオスタシス制御機構だと考えられる。ケトン体によるシグナル経路を解明することで、飢餓状態を模倣する新たな肥満病態改善薬の開発に寄与することが可能となる。