Mechanism of white adipose tissue beiging through the modulation of glycolysis

2021 Fiscal Year Final Research Report

• Project/Area Number: 19K08974
• 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: Juntendo University (2021); Niigata University (2019-2020)
• Principal Investigator: Yoshida Yohko 順天堂大学, 大学院医学研究科, 特任准教授 (00586232)
• Co-Investigator(Kenkyū-buntansha): 清水 逸平 新潟大学, 医歯学総合研究科, 特任准教授 (60444056) ; 南野 徹 新潟大学, 医歯学系, 教授 (90328063)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: ベージュ細胞 / 解糖系 / 内臓白色脂肪 / 糖代謝異常

Outline of Final Research Achievements

Brown adipose tissue (BAT) is a metabolically active organ that contributes to the thermogenic response to cold exposure. In addition, other thermogenic cells termed beige adipocytes are generated in white adipose tissue (WAT) by cold exposure. Although activation of brown/beige adipose tissue is associated with mobilization of both glucose and lipids, few studies have focused on the role of glycolytic enzymes in regulating adipose tissue function. We generated mouse models with specific deletion of the glycolytic enzyme phosphoglycerate mutase 1 (PGAM1) from adipose tissue. Deletion of Pgam1 from both BAT and WAT promoted whitening of BAT with beiging of visceral WAT, whereas deletion of Pgam1 from BAT alone led to whitening of BAT without beiging of WAT. Our results demonstrate a potential role of glycolytic enzymes in beiging of visceral WAT and suggest that PGAM1 would be a novel therapeutic target in obesity and diabetes.

Free Research Field

循環器内科学

Academic Significance and Societal Importance of the Research Achievements

本研究は脂肪組織での解糖系を抑制することでオートファジーの抑制を介して褐色脂肪様細胞（ベージュ細胞）を誘導するというベージュ細胞誘導の新たなメカニズムを明らかにしたものである。全世界で肥満人口は増えており、肥満や糖尿病は健康寿命の短縮や死亡率の上昇につながるため、これらに対する新たな治療法の開発は重要な課題である。本研究成果により、内臓白色脂肪をベージュ化し、代謝の活発な形質に転換できる可能性が示唆され、これまでにないアプローチから代謝性疾患の治療法が開発できる可能性がある。