Elucidation of the pathogenesis of NASH and hepatocellular carcinoma induced by dietary fatty acid, and development of therapeutic strategies based on its pathogenesis

2017 Fiscal Year Final Research Report

• Project/Area Number: 15K00874
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Eating habits
• Research Institution: Ehime University
• Principal Investigator: Teruki Miyake 愛媛大学, 医学部附属病院, 講師 (80573659)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Keywords: NASH / hepatocellular carcinoma / High fat diet / NOX2 / trans fatty acid

Outline of Final Research Achievements

To elucidate the mechanism of nonalcoholic steatohepatitis and hepatocellular carcinoma (HCC) caused by excessive intake of fatty acid , we analyzed the mechanism of generation of oxidative stress in obese mice induced by three different types of high fat diet, 1) high trans fatty acid, 2) high oleic acid, or 3) high palmitic acid. A number of HCC was significantly increased in high trans fatty acid fed group compared with other two groups. Further, expression of a factor which related to lipid deposition was significantly higher in the high trans fatty acid diet fed mice. The over expression of the factor by excess trans acid facilitated the accumulation of inflammatory macrophage which express NOX2 and resulted in excessive oxidative stress. On the other hand, liver specific suppression of the factor related to lipid deposition in high trans fatty acid fed mice reduced the number of inflammatory macrophages and the expression of oxidative stress in the liver.

Free Research Field

Metabology