Regulatory mechanism of ABCA1 expression involved in lipotoxicity in pancreatic beta cells.

2021 Fiscal Year Final Research Report

• Project/Area Number: 19K23970
• Research Category: Grant-in-Aid for Research Activity Start-up
• Allocation Type: Multi-year Fund
• Review Section: 0902:General internal medicine and related fields
• Research Institution: Kagawa University
• Principal Investigator: Sato Seisuke 香川大学, 医学部附属病院, 助教 (50843504)
• Project Period (FY): 2019-08-30 – 2022-03-31
• Keywords: ABCA1 / 脂肪毒性

Outline of Final Research Achievements

Since 2-Methoxyestradiol (2ME), a major metabolite of estradiol, is thought to be involved in lipotoxicity, we first investigated whether 2ME affects ABCA1 expression in HepG2 cells, a cultured hepatocyte cell line. We found that 2ME increased ABCA1 expression in HepG2 cells and decreased lipid droplets in HepG2 cells. 2ME-induced ABCA1 expression was suppressed by PI3K inhibitor and induced by increased expression of Akt and p110 downstream of PI3K, indicating the involvement of the PI3/Ak pathway. We also found that the PI3/Ak pathway is involved.

Free Research Field

ABCA1

Academic Significance and Societal Importance of the Research Achievements

国民病である糖尿病は脂肪毒性と密接に関与している。このため糖尿病をコントロールするためには脂肪毒性の特徴を把握することが重要である。細胞内の脂肪量を調節する分子としてABCA1は非常に重要なものであり、ABCA1の発現を増強すると脂肪毒性が解消され糖尿病もよくなる可能性が高い。今回女性ホルモンの代謝物である2MEがABCA1の発現を増強することを発見した。