Role of "metabolic" tissue remodeling in the pathophysiology of obesity-induced chronic inflammation

2018 Fiscal Year Final Research Report

• Project/Area Number: 16H05171
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Experimental pathology
• Research Institution: Nagoya University
• Principal Investigator: Suganami Takayoshi 名古屋大学, 環境医学研究所, 教授 (50343752)
• Research Collaborator: Itoh Michiko
• Project Period (FY): 2016-04-01 – 2019-03-31
• Keywords: 慢性炎症 / 肥満 / 非アルコール性脂肪肝炎 / マクロファージ

Outline of Final Research Achievements

In this study, to understand the molecular mechanism underlying NASH, we employed genetically obese melanocortin-4 receptor-deficient mice, which sequentially developed simple steatosis, NASH, and hepatocellular carcinoma (HCC) when they were fed a Western diet. We also develop novel accelerated animal models which exhibited NASH and HCC in the short-term. Using these animal models, we identified a unique histological structure termed “crown-like structure”, in which macrophages aggregated around dead hepatocytes, thereby accelerating tissue remodeling during the disease progression from simple steatosis to NASH. Our data suggest that CLS is useful to examine the molecular mechanisms how certain drugs ameliorated NASH.

Free Research Field

内分泌代謝学

Academic Significance and Societal Importance of the Research Achievements

近年、数多くの抗糖尿病薬が上市され、糖尿病治療は、単に血糖値を低下させるのみならず、合併症を予防することに重点が置かれるようになってきた。即ち、脂肪肝やNASHに対する抗糖尿病薬の効果が注目されている。そこで本研究では、種々の薬剤のNASHに対する薬効評価を実施した。CLSに着目することにより、治療効果の定量的評価が可能となり、作用機序の一端も明らかになるなど、今後の治療法の開発に資すると考えられた。