Regulation of metabolism and fibrosis in liver by cell-extracellular matrix physical interaction
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 |
|
Project Period (FY) |
2017-04-01 – 2020-03-31
|
Project Status |
Completed (Fiscal Year 2019)
|
Budget Amount *help |
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2019: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2017: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
|
Keywords | 肥満 / 糖尿病 / インスリン抵抗性 |
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.
|
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。
|
Report
(4 results)
Research Products
(1 results)
-
[Journal Article] Roles for cell-cell adhesion and contact in obesity-induced hepatic myeloid cell accumulation and glucose intolerance.2017
Author(s)
Miyachi Y, Tsuchiya K, Komiya C, Shiba K, Shimazu N, Yamaguchi S, Deushi M, Osaka M, Inoue K, Sato Y, Matsumoto S, Kikuta J, Wake K, Yoshida M, Ishii M, Ogawa Y
-
Journal Title
Cell Rep.
Volume: 18
Issue: 11
Pages: 2766-2779
DOI
Related Report
Peer Reviewed / Open Access / Acknowledgement Compliant