Analysis of mechanisms for NASH pathogenesis associated with endotoxin-induced dysorder of lipid metabolism

2014 Fiscal Year Final Research Report

• Project/Area Number: 25860550
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Gastroenterology
• Research Institution: Yokohama City University
• Principal Investigator: IMAJO kento 横浜市立大学, 附属病院, 助教 (30600192)
• Research Collaborator: NAKAJIMA Atsushi 横浜市立大学, 医学研究科, 教授 (30326037) ; SAITO Satoru 横浜市立大学, 医学部, 准教授 (00275041) ; OGAWA Yuji 横浜市立大学, 附属病院, 指導診療医 (20644959)
• Project Period (FY): 2013-04-01 – 2015-03-31
• Keywords: 非アルコール性脂肪肝炎 / NASH / 病態進展機序の解明 / エンドトキシン / 脂質代謝

Outline of Final Research Achievements

Gut derived endotoxin (ET) is the one of the major pathogenesis of the development of nonalcoholic steatohepatitis (NASH). We have recently demonstrated the hyper responsibility to ET in the fatty liver by increasing the expression of CD14 which is the co-receptor for ET by increase in leptin, promoting the chronic steatohepatitis even under the low-dose ET exposure in high-fat diet (HFD)-fed obese mice. However, to investigate the role of ET in human NASH pathogenesis, we must use lower dose of ET, which does not lead to liver disorder, even in HFD-fed obese mice. In this research, we found that the very low dose ET decreased hepatic microsomal triglyceride transfer protein (MTTP), key factor of lipid metabolism, led to excess accumulation of free fatty acid (FFA), result in development of NASH pathogenesis, even advanced liver fibrosis.

Free Research Field

肝臓一般