Investigation of a novel mechanism of NASH pathogenesis focused on bile acid transporters

2022 Fiscal Year Final Research Report

• Project/Area Number: 20K17014
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 53010:Gastroenterology-related
• Research Institution: The University of Tokyo
• Principal Investigator: Okushin Kazuya 東京大学, 医学部附属病院, 助教 (40753918)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: 胆汁酸トランスポーター / bile salt export pump / Gut-Liver axis / 腸内細菌叢

Outline of Final Research Achievements

To elucidate the mechanisms of non-alcoholic steatohepatitis, a mouse model was investigated in which the expression of the bile acid transporter bile salt export pump (BSEP), which is expressed only in the liver, was suppressed. When the mice were fed a high-fat diet, they presented reduced body weight gain and liver steatosis, as well as changes in the expressions of a wide range of metabolism-related genes in the liver and intestinal tract. Furthermore, characteristic changes in the gut microbiota were also observed. These results suggest that BSEP plays an important role in the Gut-Liver axis, which is a functional link among the liver, the intestinal tract, and all the organs in the body.

Free Research Field

肝臓病学

Academic Significance and Societal Importance of the Research Achievements

非アルコール性脂肪肝炎は肝臓のみならず、糖尿病や大血管イベントにも関与が示唆される重大な疾患であるが、その病態は未だに不明な点が多く、有効な治療は確立していない。
本研究成果は、胆汁酸トランスポーターであるbile salt export pump (BSEP)が、肝臓における胆汁酸代謝のみならず、腸管や腸内細菌叢、そして全身まで影響を及ぼすことを示した重要な知見と考えられる。
BSEPがこれらの変化を生じる詳細なメカニズムの解明は、科学的に重要な知見であるのみならず、BSEPを標的として非アルコール性脂肪肝炎に加えて全身の代謝性疾患の病態解明および治療法の開発に寄与することが期待される。