PPAR-alpha mediated molecular mechanisms involved in spontaneous hepatocarcinogenesis among NASH mouse model

2017 Fiscal Year Final Research Report

• Project/Area Number: 15K09010
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Gastroenterology
• Research Institution: Kochi University
• Principal Investigator: SAIBARA Toshiji 高知大学, 教育研究部医療学系臨床医学部門, 教授 (60145125)
• Co-Investigator(Kenkyū-buntansha): 耕崎 拓大 高知大学, 教育研究部医療学系臨床医学部門, 講師 (00332833) ; 戸田 勝巳 高知大学, 教育研究部医療学系基礎医学部門, 准教授 (40197893) ; 水田 洋 高知大学, 教育研究部医療学系臨床医学部門, 助教 (70527605)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Keywords: PPAR-alpha / melanocortin receptor / insulin resistance / fatty liver / IL-6 / NASH / hepatocellular carcinoma / knockout mouse

Outline of Final Research Achievements

Both MC4R KO mouse and MC4R-PPAR-alpha double KO mouse showed progressive impairment of insulin sensitivity and enhanced mRNA expression of genes involved in fatty acid synthesis, fatty acid beta and omega oxidation, inflammation, and scavenger receptors in addition to IL-6 mRNA. However, there was a significant difference in neoplastic nodule size and number among these two KO mice, i.e., averaged diameter and averaged number of tumor were significantly fewer in MC4R-PPAR-alpha double KO mouse than in MC4R KO mouse. This observation suggests that PPAR-alpha mediated mechanisms are involved in spontaneous hepatocarcinogenesis among NASH mouse models.

Free Research Field

消化器病学