Role of endocrine FGF in digestion and metabolic regulation

2018 Fiscal Year Final Research Report

• Project/Area Number: 16K09800
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Endocrinology
• Research Institution: Nagoya City University (2017-2018); Kyoto University (2016)
• Principal Investigator: Tanaka Tomohiro 名古屋市立大学, 大学院医学研究科, 准教授 (20402894)
• Project Period (FY): 2016-04-01 – 2019-03-31
• Keywords: FGF / 脂質代謝 / NASH / 膵液 / オミックス

Outline of Final Research Achievements

Among endocrine FGFs, we here studied the functional role of FGF19 in pancreatic exocrine function and in the pathogenesis of non-alcoholic steatohepatitis. By collecting pancreatic juice from rats, we discovered that FGF19 or FGF21 injection lead to increased rate of lipase secretion into pancreatic juice. To investigate whether FGF19 effects on pancreas is mediated by beta Klotho, a specific co-receptor of FGF19, we newly generated beta Klotho knockout rats by CRISPR/Cas9 system. Although we have established a knockout rat, we could not efficiently obtain sufficient numbers of homozygous knockout rats, making the pancreatic juice collection pending until enough numbers of rats are available. We performed hisologic as well as transcriptomic analysis of the liver in beta Klotho knockout mice and found that the mice are good model of non-alcoholic steatohepatitis in humans from the aspect of not only steatosis, but of inflammation and hepatocyte injury.

Free Research Field

内分泌代謝内科学

Academic Significance and Societal Importance of the Research Achievements

本研究により、脂質や脂溶性栄養素の消化と吸収、体内分配を統一的に制御するFGF19 - beta Klothoシステムの生理的、病態生理的意義が明らかとなった。これまで膵消化酵素の分泌を制御するホルモンとしては、セクレチンやコレシストキニンが知られていたが、本研究により回腸遠位から分泌される新しいホルモンFGF19が膵液量の増加を伴わずに膵消化酵素、特にリパーゼの分泌を促進することが明らかとなった。また近年、我が国においても有病率の増加が懸念されている非アルコール性脂肪性肝炎（NASH）の病態における胆汁酸・脂質代謝異常の実体が明らかとなった。