Analyses of involvement mechanism of NRF2 and mitochondrial abnormality in pathophysiology of NASH

Research Project

Project/Area Number	25460983
Research Category	Grant-in-Aid for Scientific Research (C)
Allocation Type	Multi-year Fund
Section	一般
Research Field	Gastroenterology
Research Institution	Niigata University
Principal Investigator	KAWAI Hirokazu 新潟大学, 医歯学総合病院, 講師 (80419291)
Co-Investigator(Kenkyū-buntansha)	SUDA Takeshi 新潟大学, 医歯学総合病院, 教授 (10361916)
Project Period (FY)	2013-04-01 – 2016-03-31
Project Status	Completed (Fiscal Year 2015)
Budget Amount *help	¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000) Fiscal Year 2015: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000) Fiscal Year 2014: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000) Fiscal Year 2013: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000)
Keywords	非アルコール性脂肪肝炎 / 脂肪肝 / ミトコンドリアDNA / 酸化ストレス / ダイエット / NASH / ミトコンドリアDNAコピー数 / 活性酸素種 / ミトコンドリア生合成 / マイトファジー / NAFLD / Nrf2
Outline of Final Research Achievements	An increasing tendency of mitochondrial DNA (mtDNA) copy number was found in the liver of a rodent model of fatty liver, however the number was normalized with diet intervention. In contrast, mtDNA copy number was decreased in the liver of a rodent model of nonalcoholic steatohepatitis (NASH). MtDNA copy number in these models appeared to be regulated by altering a balance between expression levels of genes related to biogenesis and degradation of mitochondria. It has been revealed that pathophysiological progression in NASH is closely related to oxidative stress along with alteration of mtDNA copy number.