The significance of activation of macrophage in the development of nonalcoholic steatohepatitis

2013 Fiscal Year Final Research Report

• Project/Area Number: 23590360
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Pathological medical chemistry
• Research Institution: St. Marianna University School of Medicine
• Principal Investigator: NAGAI Yoshio 聖マリアンナ医科大学, 医学部, 講師 (90402718)
• Co-Investigator(Kenkyū-buntansha): NISHIO Yoshihiko 鹿児島大学, 医学部, 教授 (40281084)
• Co-Investigator(Renkei-kenkyūsha): YOSHIZAKI Takeshi 滋賀医科大学, 医学部, 特任助教 (20510324)
• Project Period (FY): 2011 – 2013
• Keywords: NASH / TLR4

Research Abstract

We established a nonalcoholic steatohepatitis (NASH) model in vitro by isolating peritoneal macrophages and primary hepatocytes from the mouse variant of type 4 Toll-like receptor (TLR4) (C3H/HeJ) and its wild-type (C3H/HeN), respectively. The isolated macrophages and hepatocytes were co-cultured with a combination of 2 x 2 in the wild type and the mutant to investigate the phosphorylation of Akt in response to insulin stimulation. Hepatic insulin resistance occurred regardless of the type of hepatocytes and macrophages, simply under the co-cultured environment. These results suggest that the migration of macrophages near the hepatocytes is an essential factor to induce hepatic insulin resistance.