Elucidation of pathogenic mechanism of NASH and developments for diagnostic markers focusing on oxidized HDL

2021 Fiscal Year Final Research Report

• Project/Area Number: 19K20174
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 59040:Nutrition science and health science-related
• Research Institution: Hokkaido University
• Principal Investigator: Sakurai Toshihiro 北海道大学, 保健科学研究院, 准教授 (60707602)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: HDL / 酸化 / ミトコンドリア / NASH

Outline of Final Research Achievements

The link between nonalcoholic steatohepatitis (NASH) and oxidized HDL remains unclear. The purpose of this task was to verify how oxidized HDL is involved in the pathogenic mechanism of NASH by biochemical experiments using cultured human hepatocytes. As a result, we found the following: (1) Oxidized HDL forms lipid droplets in cultured liver cells, and the lipid droplets are oxidized; (2) Fatty acid synthesis and lipid droplet synthesis may be suppressed; (3) Changes in mitochondrial morphology; (4) Promotion of expression of inflammation-related genes. From the above, it was suggested that oxidized HDL may bring about changes in mitochondrial metabolism as well as lipid metabolism. In the future, we would like to continue to elucidate the full picture of the response of hepatocytes to oxidative HDL stimulation.

Free Research Field

健康科学

Academic Significance and Societal Importance of the Research Achievements

ヒト肝培養細胞を用いた研究で、酸化HDL刺激では脂肪滴の形成や炎症、酸化ストレスを促進することだけでなく、ミトコンドリア生合成に関連する遺伝子群の低下が見られ、ミトコンドリアの形態変化の一端を明らかにすることができた。これらの結果は本研究で得た重要な知見であり、今後の酸化HDL研究の進展を加速させるものと考えられた。今後もこの研究領域を深め、非アルコール性脂肪性肝障害や非アルコール性脂肪性肝炎などの生活習慣病などの病態との関連性を追求していきたいと考えている。