Regulation of macrophage function by adipose derived secreted protein and its involvement in NASH

2019 Fiscal Year Final Research Report

• Project/Area Number: 18K16205
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 54040:Metabolism and endocrinology-related
• Research Institution: The University of Tokushima
• Principal Investigator: KURODA Masashi 徳島大学, 大学院医歯薬学研究部(医学域), 特任助教 (00803579)
• Project Period (FY): 2018-04-01 – 2020-03-31
• Keywords: メタボリックシンドローム / 肥満 / 炎症 / 線維化 / NASH / アディポサイトカイン

Outline of Final Research Achievements

Excessive visceral fat is known to promote hepatic inflammation and fibrosis, and involved in the progression from simple steatosis to NASH (Non-Alcoholic Steatohepatitis). Based on DNA microarray analysis, we have found that secretary protein, MFG-E8 (Milk fat Globule EGF-8) was highly expressed in white adipose tissue from obese mouse model. In this study, we aimed to investigate the role of MFG-E8 in the pathogenesis of NASH.
We creased a murine model of NASH with MFG-E8 knocked out mice, and examined hepatic gene expressions and performed histological analysis. In knockout mice, the expressions of pro-inflammatory cytokines, activated macrophage marker genes and type II collagen were suppressed. Histological analysis revealed that macrophages infiltration into liver and hepatic fibrosis were suppressed, and overall disease activity score was significantly improved.

Free Research Field

代謝栄養学、分子生物学

Academic Significance and Societal Importance of the Research Achievements

内臓脂肪型肥満がNASH病態において重要であることは様々な疫学的研究より明らかである。一方でその分子メカニズムは十分に明らかでないため、治療は栄養指導や運動療法など減量を目的としたものであり、NASH病態を直接的に標的としたものは少ない。
本研究によりNASHにおける肝臓-脂肪の分子基盤を明らかとすることは予防法や治療法確立の上で必須である。また、近年ではNASHに起因する肝細胞癌が増加し、最も重要な発がん危険因子は肝線維化である。MFG-E8とNASH線維化との関連を解明する本研究は新たな発癌リスク因子の提示・早期発見に役立つ可能性がある。