Mechanism of exacerbation of nonalcoholic fatty liver disease by the interaction of animal lipid components

2021 Fiscal Year Final Research Report

• Project/Area Number: 20K22165
• Research Category: Grant-in-Aid for Research Activity Start-up
• Allocation Type: Multi-year Fund
• Review Section: 0108:Sociology and related fields
• Research Institution: Tohoku University (2021); Ochanomizu University (2020)
• Principal Investigator: Arisawa Kotoko 東北大学, 薬学研究科, 助教 (00813122)
• Project Period (FY): 2020-09-11 – 2022-03-31
• Keywords: 酸化コレステロール / 脂肪毒性 / NASH / 飽和脂肪酸 / 小胞体ストレス / 生体膜

Outline of Final Research Achievements

In this study, we demonstrated at the cultured cell level that the accumulation of saturated fatty acids and oxidized cholesterol, which are abundant in animal products, in hepatocytes synergistically exacerbates liver injury. Among the oxidized cholesterol, 25-hydroxycholesterol (25-OH) was found to enhance the ER stress response induced by saturated fatty acids and cell death via apoptosis in hepatocytes. In addition, the addition of 25-OH decreased intracellular fatty acid unsaturation. Since endoplasmic reticulum stress is regulated by the saturated/unsaturated fatty acid/unsaturated fatty acid ratio of the plasma membrane, it was suggested that the change in membrane unsaturation caused by the addition of 25-OH enhanced lipotoxicity.

Free Research Field

脂質代謝

Academic Significance and Societal Importance of the Research Achievements

飽和脂肪酸と酸化コレステロールは、アルコール性脂肪肝炎(NASH)の病態の肝臓において特徴的に多く見られ、またNASH患者の食嗜好性からも過剰摂取となり がちな脂質成分である。これらの脂質は、それぞれ単独では肝臓における炎症や酸化ストレス、細胞死などに寄与していることが報告されているが、肝臓に同時に存在する場合の影響については知られていなかった。本研究では、飽和脂肪酸と酸化コレステロールの肝細胞への蓄積が、相乗効果的に肝障害を増悪する可能性を明らかにした。