Integrative Medicice Focused on the Receptor Biniding Molecule for Obesity and Metabolic Syndrome

2017 Fiscal Year Final Research Report

• Project/Area Number: 16K19558
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Endocrinology
• Research Institution: Yokohama City University
• Principal Investigator: Kengo AZUSHIMA 横浜市立大学, 医学研究科, 客員研究員 (00760381)
• Research Collaborator: TAMURA Kouichi
• Project Period (FY): 2016-04-01 – 2018-03-31
• Keywords: 脂肪細胞 / 骨格筋 / インスリン抵抗性 / 肥満症 / 受容体 / レニン-アンジオテンシン系

Outline of Final Research Achievements

Angiotensin II type 1 receptor (AT1R) is a major player in the signal transduction of renin-angiotensin system, and the overactivation of this signaling contributes to the progression of visceral obesity. AT1R-associated protein (ATRAP) promotes AT1R internalization along with the suppression of overactivation of tissue AT1R signaling. We demonstrated that the enhancement of ATRAP in adipose tissue ameliorated high-fat diet-induced visceral obesity and insulin resistance via the attenuation of overactivated AT1R signaling and adipose inflammation. Furthermore, we revealed that low-dose angiotensin II administration could promote the insulin resistance even in a lean type, and this finding was mainly caused by the dysfunction of glucose uptake in skeletal muscle due to increased oxidative stress. The enhancement of ATRAP in skeletal muscle ameliorated this insulin resistance in a lean type via the attenuation of overactivated AT1R signaling and oxidative stress in skeletal muscle.

Free Research Field

慢性腎臓病、糖尿病、肥満症、高血圧症