Aberrant postprandial glucose/triglyceride spikes promote premature aging of hematopoietic stem/progenitor cells

2020 Fiscal Year Final Research Report

• Project/Area Number: 18K08053
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 53020:Cardiology-related
• Research Institution: Kansai Medical University
• Principal Investigator: IWASAKI Masayoshi 関西医科大学, 医学部, 研究医員 (30548706)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Keywords: 食後高血糖 / 食後高中性脂肪血症 / 幹細胞老化

Outline of Final Research Achievements

Bone marrow-derived endothelial progenitor cells (EPCs) contribute to endothelial repair and angiogenesis. Reduced number of circulating EPCs is associated with future cardiovascular events. We tested whether dysregulated glucose and/or triglyceride (TG) metabolism has an impact on EPC homeostasis.
Our human study revealed that postprandial hyperglycemia is negatively correlated with circulating EPC number and this correlation is further enhanced in the presence of postprandial hypertriglyceridemia (hTG). We therefore examined the effect of glucose/TG spikes on bone marrow lineage-sca-1+c-kit+ (LSK) cells in mice, because primitive EPCs constitute a fraction of bone marrow LSK cells. Repetitive glucose+lipid (GL) spikes, but not glucose (G) or lipid (L) spikes alone, induced premature aging of LSK cells, and this phenomenon was reversible after cessation of GL spikes. G spikes and GL spikes differentially affected transcriptional program of LSK cell metabolism and differentiation.

Free Research Field

循環器疾患・糖尿病

Academic Significance and Societal Importance of the Research Achievements

本研究では食後高血糖＋食後高中性脂肪血症が骨髄中のEPCの転写調節に広範な影響を及ぼし、EPCの老化を急速に促進させることを確認した。また、この食後高血糖＋食後高中性脂肪血症による老化促進効果は可逆性である可能性が示唆された。この検討によって動脈硬化性疾患の発症・進展における食後高血糖・食後高中性脂肪血症の新たな病態生理学的意義が明らかになること、そして新たな治療標的の発見につながることが期待される。