Validation of the efficacy of erythropoietin for the treatment of non-alcoholic fatty liver disease

2022 Fiscal Year Final Research Report

• Project/Area Number: 20K17517
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 54040:Metabolism and endocrinology-related
• Research Institution: Kyoto Prefectural University of Medicine
• Principal Investigator: Tsuma Yusuke 京都府立医科大学, 医学(系)研究科(研究院), 特任助教 (60843290)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: エリスロポエチン / 非アルコール性脂肪性肝疾患 / 肥満 / 褐色細胞

Outline of Final Research Achievements

There is no well-established drug treatment for non-alcoholic fatty liver disease (NAFLD). Erythropoietin (EPO), a glycoprotein that stimulates erythropoiesis in bone marrow, is widely used for treatment of renal anemia and anemia of prematurity. Recently, various off-target effects of EPO have been reported, including anti-obesity and anti-diabetes effects. In our previous study, we showed that EPO improves lipid metabolism in NAFLD, but the mechanism has not been fully elucidated.

In this study, we hypothesized that EPO’s improvement of NAFLD is mediated by activating brown fat. However, in animal studies using two existing drugs that are known to activate brown fat, they did not reduce liver inflammation, suggesting that brown fat may not mediate the NAFLD improvement by EPO.

Free Research Field

小児内分泌

Academic Significance and Societal Importance of the Research Achievements

褐色脂肪の機能亢進/低下がNAFLDの病態の軽減/増悪に寄与する報告がある。申請者の先行研究（EPOのNAFLD改善作用）と、申請者らのグループの先行研究（EPOの褐色脂肪活性化作用）を踏まえてEPOのNAFLD改善に褐色脂肪が関与すると仮説を立て検証した。しかし、褐色脂肪活性化の作用がある既存の薬剤2種類は、肥満モデルマウスの肝臓炎症を改善しなかった。よって、EPOが直接的に肝臓に作用もしくは他臓器などを介して肝臓に作用し、NAFLD改善を導いた可能性が示唆される。EPOのNAFLDにおける臨床応用の観点において、EPOのNAFLDに対する作用機序の一つを証明した点で社会的意義がある。