Regulation of metabolism and fibrosis in liver by cell-extracellular matrix physical interaction

2019 Fiscal Year Final Research Report

• Project/Area Number: 17K09820
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Metabolomics
• Research Institution: University of Yamanashi
• Principal Investigator: Tsuchiya Kyoichiro 山梨大学, 大学院総合研究部, 講師 (60451936)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Keywords: 肥満 / 糖尿病

Outline of Final Research Achievements

Obesity promotes infiltration of inflammatory cells into various tissues, leading to parenchymal and stromal cell interaction and development of cellular and organ dysfunction. Liver sinusoidal endothelial cells (LSECs) are the first cells that contact portal blood cells and substances in the liver. Here, we find that LSECs are involved in obesity-associated accumulation of myeloid cells via VLA-4-dependent cell-cell adhesion. VLA-4 blockade in mice fed a high-fat diet attenuated myeloid cell accumulation in the liver to improve hepatic inflammation and systemic glucose intolerance. Ex vivo studies further show that cell-cell contact between intrahepatic leukocytes and parenchymal hepatocytes induces gluconeogenesis via a Notch-dependent pathway. These findings suggest that cell-cell interaction between parenchymal and stromal cells regulates hepatic glucose metabolism and offers potential strategies for treatment or prevention of obesity-associated glucose intolerance.

Free Research Field

内分泌・代謝学

Academic Significance and Societal Importance of the Research Achievements

炎症細胞と肝類洞内皮細胞、ならびに炎症細胞と肝実質細胞間の物理的相互作用が新しい糖尿病の治療標的になることが期待される。