Elucidating a role of cross-talk between endothelial cell and adipocyte in the maintenace of adipose tissue homeostasis

2018 Fiscal Year Final Research Report

• Project/Area Number: 16K09524
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Cardiovascular medicine
• Research Institution: Kobe Pharmaceutical University
• Principal Investigator: KOJI IKEDA 神戸薬科大学, 薬学部, 准教授 (90423871)
• Project Period (FY): 2016-04-01 – 2019-03-31
• Keywords: 肥満 / メタボリック症候群 / 脂肪組織 / インスリンシグナル / 血管新生

Outline of Final Research Achievements

We have identified two candidate genes, Nrg4 and Fam13a, which are involved in the pathogensis of obesity and its-related metabolic disorders. We found that Fam13a accentuated adipocyte insulin signaling by inhibiting proteasomal degradation of IRS-1. Genetic deletion of Fam13a improved systemic metabolic health in mice through preserving adipose tissue insulin signaling. On the other hand, we revealed that Nrg4 is a novel angiogenic adipokine. Loss of Nrg4 caused reduction in adipose tissue vasculatures, and exacerbated obesity and its-related metabolic disorders. Because Fam13a and Nrg4 expression in adipocytes substantially decreased during obesity, activation of Fam13a and/or Nrg4 has a therapeutic potential for obesity-related metabolic disorders.

Free Research Field

血管生物学

Academic Significance and Societal Importance of the Research Achievements

肥満やメタボリック症候群は、動脈硬化を進展させて心血管疾患の発症リスクを増大させるため、その健康被害は甚大です。私達はこれら病態に関わる２つの遺伝子（Fam13aとNrg4）を発見し、その機能を解明しました。本研究成果によって、肥満・代謝異常の未知の仕組みが明らかになったとともに、Fam13aおよびNrg4の活性化が肥満・メタボリック症候群の発症を予防する効果が示されたことは大変意義深いです。